2ndNa'onalColloquiumforCombinedDVM/PhDBiomedicalScien'sts

August1-2,2018

CollegeofVeterinaryMedicine&BiomedicalSciencesTexasA&MUniversity

HostOrganizerRogerSmith,D.V.M.,Ph.D. TexasA&MUniversity

SessionChairsMichaelAtchison,PhD UniversityofPennsylvania

XinbinChen,BVSc,PhD UniversityofCalifornia,Davis

EdwardHoover,DVM,PhD ColoradoStateUniversity

HélèneMarquis,DVM,PhDCornellUniversity

TableofContents

ListofSponsors 3......................................................

Welcome 4................................................................

ScheduleofEvents 5.................................................

SpeakerBiographies 6..............................................

StephanieMurphy,VMD,PhD 6................................

Col.JenniferM.Kishimori,DVM,PhD 7....................

TheresaAlenghat,VMD,PhD 8.................................

ErinChu,DVM,PhD 9................................................

TimKurt,DVM,PhD 10..............................................

RoxannBrooksMotroni,DVM,PhD 11......................

NoelleNoyes,DVM,PhD 12......................................

ColloquiumMap 13..................................................

PosterLayout 14.......................................................

StudentAbstracts 15................................................

ListofPar\cipants 64................................................

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ListofSponsors

TheBurroughsWellcomeFund

TexasA&MUniversityCollegeofVeterinaryMedicine&BiomedicalSciences

ColoradoStateUniversityCollegeofVeterinaryMedicine&BiomedicalSciences

CornellUniversityCollegeofVeterinaryMedicine

MississippiStateUniversityCollegeofVeterinaryMedicine

UniversityofCalifornia-DavisSchoolofVeterinaryMedicine

UniversityofPennsylvaniaSchoolofVeterinaryMedicine

Virginia-MarylandCollegeofVeterinaryMedicine

Associa\onofAmericanVeterinaryMedicalColleges

IowaStateUniversityCollegeofVeterinaryMedicine

LouisianaStateUniversitySchoolofVeterinaryMedicine

NorthCarolinaStateCollegeofVeterinaryMedicine

UniversityofIllinoisCollegeofVeterinaryMedicine

TheOhioStateUniversityCollegeofVeterinaryMedicine

MichiganStateUniversityCollegeofVeterinaryMedicine

We sincerely appreciate the support of our sponsors. Due to their generosity, we were able to invite all combined degree students, without charging a registration fee.

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Welcome

August 1, 2018

Dear Friends & Colleagues:

Howdy and welcome to the 2nd National Colloquium for Combined DVM/PhD Biomedical Scientists at the Texas A&M College of Veterinary Medicine & Biomedical Sciences. The Colloquium had its origin at the National Veterinary Scholars Symposium, where dedicated veterinary educators came together to create an exchange of ideas and best practices for training veterinary scientists. From a meeting of several faculty members, it grew into the first Colloquium, hosted last year by Dr. Mark Simpson at the National Institutes of Health. We are honored to be hosting the second Colloquium at Texas A&M.

As this expanded to a Colloquium, we had the opportunity to feature some of our outstanding combined degree students by inviting a few of them to present their scientific findings. Everyone found it exciting to hear their impressive work, and this year we were able to include poster presentations by nearly all of our combined degree students, in addition to talks. The students are also continuing to develop networks among the different programs. With their valuable input, we have invited a panel of recent combined degree graduates to sit on a panel focused on careers and life after the dual degrees. It will be exciting to see where this fledgling Colloquium goes in the next few years.

Veterinary clinician scientists are an important component of the nation’s research effort on so many fronts: human, animal and environmental health, therapeutic discoveries, fundamental discovery science, and more. But the veterinary community’s scientific contributions can become even greater. It is incumbent upon veterinary curricula and faculty members to encourage the research track for our students, to nurture those with research interests and scientific curiosity, and to provide strong training programs that allow them to succeed. Combined degree programs are one of several paths to success as veterinary clinician scientists and are certainly the best path for many students.

The clinical training that veterinary students receive provide them the tools and understanding of health and disease, both in individuals and in populations. The training is multi-disciplinary: physiology, pathology, immunology, microbiology, parasitology, pharmacology, public health. Students are exposed to the whole of comparative medicine and surgery. They graduate equipped to engage scientists across disciplines, engagement that is essential in today’s scientific research effort.

This Colloquium celebrates the quality of our students and our training programs to excel in multi-disciplinary, collaborative and comparative biomedical research. We welcome you to Aggieland and wish you a great Colloquium.

Wishing you the best,

Roger Smith III, DVM, PhD Professor, Department of Veterinary Pathobiology College of Veterinary Medicine & Biomedical Sciences Texas A&M University

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ScheduleofEvents

Wednesday,August1

7:00PM VENI101 InformalGathering&BuffetDinner(cashbar)

Thursday,August2

7:00AM VENI101 Breakfast

8:30AM VENI106A Dr.RogerSmith–WelcomeAddressandHouse-KeepingIssues

8:45AM VENI106A KattiHorng,UniversityofCalifornia,Davis

9:00AM VENI106A KristenDavenport,ColoradoStateUniversity

9:15AM VENI106A EmilyMackey,NorthCarolinaStateUniversity

9:30AM VENI106A EmilyPope,UniversityofMinnesota

9:45AM Break

10:15AM VENI106A Dr.StephanieMurphy—byvideoconferenceDirectoroftheDivisionofComparativeMedicineOfficeofResearchInfrastructureProgramsDivisionofProgramCoordination,Planning,andStrategicInitiativesOfficeoftheDirector,NationalInstitutesofHealth

10:45AM VENI106A FrancesChen,CornellUniversity

11:00AM VENI106A ElinorWillis,UniversityofPennsylvania

11:15AM: VENI106A Col.JenniferM.Kishimori OfficeoftheAssistantSecretaryDefenseforHealthAffairsHealthProtectionReadinessandOversightDirector,Chemical,Biological,RadiologicalandNuclearMedicalCountermeasuresPolicy

11:45AM VENI101 Lunch

1:15PM VENI106A PaneldiscussionswithDr.TheresaAlenghatDr.ErinChu Dr.TimKurt Dr.RoxannBrooksMotroni Dr.NoelleNoyes

3:45PM VENIFoyer PosterSession&AfternoonRefreshmentBreak

4:15PM VENI106A Dr.HaroldWatson—T-DirectorsMeeting(videoconference)

5:30PM VENI106A Closingremarks

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SpeakerBiographies

StephanieMurphy,VMD,PhD

DirectoroftheDivisionofCompara\veMedicineOfficeofResearchInfrastructureProgramsDivisionofProgramCoordina\on,Planning,andStrategicIni\a\ves OfficeoftheDirectorNa\onalIns\tutesofHealth

Dr. Murphy received both her V.M.D. and Ph.D. from the University of Pennsylvania and completed a comparative medicine postdoctoral fellowship at The Johns Hopkins University School of Medicine, along with all of the requirements to gain the status of Diplomate of the American College of Laboratory Animal Medicine. Dr. Murphy was named the Director of the Division of Comparative Medicine (DCM), Office of Research Infrastructure Programs (ORIP) in June 2014. DCM’s mission is to develop veterinary scientists as part of the workforce that supports and contributes to animal-based research and resources as well as to support biomedical research in the form of diverse models of human disease using vertebrate and non-vertebrate animals or cultured cells. She joined ORIP from the Oregon Health and Science University (OHSU), where she was a Professor of Anesthesiology and Perioperative Medicine (APOM), with joint appointments in Behavioral Neuroscience and Comparative Medicine. Dr. Murphy has published numerous articles, reviews and book chapters related to her research and clinical interests regarding sex differences and the role of sex steroids in stroke as well as development and management of animal models related to stroke and women’s health.

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Col.JenniferM.Kishimori,DVM,PhDUSArmyVeterinaryCorps Director,Chemical,Biological,RadiologicalandNuclear(CBRN)MedicalCountermeasuresPolicyOfficeoftheAssistantSecretaryDefenseforHealthAffairs(OASD(HA))HealthReadinessPolicyandOversight(HRP&O)

Colonel (COL) Jennifer M. Kishimori serves as theDirector, Chemical, Biological, Radiological and Nuclear(CBRN)MedicalCountermeasuresPolicyintheOfficeofthe Assistant Secretary of Defense for Health Affairs,HealthReadinessPolicyandOversight. Inthisrole,sheleads DoD health policy development and oversightefforts in CBRN medical product research anddevelopment,coordina\ngwithinDoDComponentsandacross the Interagency to ensure readiness of U.S.Forces against the effects of weapons of massdestruc\on.COLKishimorialsoservesastheVeterinaryBiomedical Sc ien\st (D.V.M./Ph.D.) (Mi l i taryOccupa\onalSpecialty64E)ConsultanttotheU.S.ArmySurgeon General, and oversees the recruitment,professionaldevelopment,andassignmentofofficersinthisspecialty.

COLKishimorigraduated in1992withaB.A. inBiologyfrom the Johns Hopkins University and wascommissioned a Second Lieutenant through the ArmyROTC Program (Dis\nguishedMilitary Graduate). Shereceived a D.V.M. from the North Carolina StateUniversityCollegeofVeterinaryMedicinein2003,andaPh.D. inMicrobiologyfromtheUniversityofHawaii in 2010 through the U.S. Army’s Long Term Health Educa\on and Training Program. COLKishimoripreviouslyservedintheU.S.ArmyasaMilitaryIntelligenceOfficerinKoreaandinthe101stAirborne Division (Air Assault), prior to comple\ng veterinary school and entering the U.S. ArmyVeterinaryCorps.

Overthepast15years,COLKishimori’sserviceasaU.S.ArmyVeterinarianhasrangedfromveterinaryclinical medicine and food protec\on missions at Fort Bragg, North Carolina and Yongsan ArmyGarrison, Seoul, Korea to military research, development and acquisi\on as a 64E VeterinaryBiomedicalScien\st.Shehasservedasabenchresearcher,DeputyVirologyDivisionChiefandMilitaryDeputy to the Scien\fic Director at the U.S. Army Medical Research Medical Research Ins\tute ofInfec\ous Diseases, suppor\ng the research and development of medical countermeasures againstselect biological agents and toxins. She also served as Deputy Director and Director, Force HealthProtec\onDivisionattheU.S.ArmyMedicalMaterielDevelopmentAc\vity,whereherteamprovidedinves\ga\onalmedicalcountermeasuresupporttoOpera\onUnitedAssistanceduringthe2014WestAfricaEbolaOutbreakResponse.

COLKishimori is a graduateof theU.S.Army’sCommandandGeneral StaffOfficers' Courseand theNavalPostGraduateSchool’sAdvancedAcquisi\onProgram.Sheiscer\fiedinScienceandTechnologyManagement (Level III) from the Defense Acquisi\on University and is a Project ManagementProfessional.

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TheresaAlenghat,VMD,PhD

AssistantProfessorDepartmentofPediatricsUniversityofCincinna\

Dr. Theresa Alenghat is an Assistant Professor in the Immunobiology Division at Cincinnati Children’s Hospital Medical Center. Dr. Alenghat received her veterinary degree and pathology residency training at the University of Pennsylvania. She also did her PhD in molecular biology as well as postdoctoral work at the same institution working with Drs. Mitch Lazar and David Artis, leaders in the fields of metabolism and immunology, respectively. She joined Cincinnati Children’s in 2014 and has established a research program to investigate molecular mechanisms that regulate the host-microbe relationship and how this level of regulation affects susceptibility to infection, inflammatory bowel disease, and obesity. Dr. Alenghat oversees a Gnotobiotic Mouse Facility and play an active role in the Immunology, Cell Biology, and Developmental Biology Graduate Groups and the Medical Scientist Training Program. Her research includes investigation of epigenomic pathways that regulate epithelial and immune cell homeostasis in the context of the signals from the intestinal microbiota. Her work in this area has been published in multiple high profile journals including Nature, Science, Nature Immunology, and Immunity. At this early stage, Dr. Alenghat has also already been successful in securing substantial extramural funding from the NIH, Burroughs Wellcome Fund, Pew Charitable Trust, and the Crohn's & Colitis Foundation.

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ErinChu,DVM,PhD

SeniorVeterinaryGene\cistEmbarkVeterinary,Inc

Erin graduated from Cornell’s Combined DVM/PhD program in 2017, having tracked equine in veterinary school, then pursuing her PhD in the lab of Dr. Paul Soloway with a focus on long noncoding RNA-mediated epigenetic mechanisms using the mouse model. Throughout her PhD, Erin continued to practice with local high-quality, high-volume spay neuter and wellness programs. She also began consulting with Embark, a then seed-grant stage Cornell-affiliated startup. After graduating in 2017, she accepted on full-time offer with Embark in the versatile position of Senior Veterinary Geneticist. Within Embark, Erin acts the liaison between Embark’s Research and Development and Science and Marketing spheres. She is heavily involved in product design and development, and helps to shape research studies and collaborations with breed clubs and rescue organizations. Erin is particularly interested in scientific and medical outreach and communication, especially as it applies to web-based data collection and citizen science, and owes much of her daily motivation and success to her Labrador-Shepherd mix, Shiloh.

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TimKurt,DVM,PhD

Scien\ficProgramDirectorFounda\onforFoodandAgricultureResearch

Dr. Tim Kurt establishes important collaborations between industry, academia, non-profits and other partners to address critical challenges facing agriculture. Dr. Kurt develops projects in FFAR’s Protein Challenge and Rapid Outcomes from Agriculture Research programs at FFAR, and his portfolio includes research that ranges from the basic biological sciences to applied technologies in animal health and wellbeing, disease surveillance and response, genetics and sustainability. He is passionate about using science to advance the wellbeing of society.

Dr. Kurt received his DVM and PhD degrees from the combined degree program at Colorado State U n i v e r s i t y, w h e r e h e s t u d i e d s p o n g i f o r m encephalopathies (prions) such as BSE/mad cow, scrapie and CWD – diseases which can be transmitted between livestock, wildlife and humans. Prior to joining FFAR in 2016, he worked as a Research Scientist at the Center for Veterinary Sciences and Comparative Medicine at the University of California San Diego (UCSD), where he received awards from the NIH, the Morris Animal Foundation and the AVMA/AVMF.

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RoxannBrooksMotroni,DVM,PhD

Na\onalProgramLeaderforAnimalHealthUSDAAgriculturalResearchSta\on

Roxann Brooks Motroni is the National Program Leader for Animal Health at the U.S. Department of Agriculture (USDA), Agricultural Research Service (ARS). In this role, she sets the strategic direction and national coordination for USDA’s intramural research program focused on animal health research which includes some zoonotic diseases with 9 research locations in Ames, Iowa; Clay Center, Nebraska; Athens, Georgia; Orient Point; New York, Beltsville, Maryland; Pullman, Washington; Mississippi State, Mississippi; Albany, CA and Manhattan, Kansas. Prior to this position, she was a program manager at the U.S. Department of Homeland Security (DHS), Chemical and Biological Defense Division (CBD) in the Agriculture Defense Branch. Her program funded between $10-15M per annum to provide discovery, ear ly deve lopment , tes t and eva luat ion o f countermeasures for foreign animal diseases that could have catastrophic impacts on the U.S. economy. She holds a Doctorate of Veterinary Medicine and a PhD in Comparative Pathology from the University of California, Davis and is a practicing food animal veterinarian.

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NoelleNoyes,DVM,PhD

Assistant Professor Department of Veterinary Population MedicineUniversity of Minnesota

Dr. Noelle Noyes is a veterinary epidemiologist in the Veterinary Population Medicine Department at the University of Minnesota. Noelle received her BA in European Studies from Amherst College, with a secondary concentration in Asian Languages and Civilizations. She received her MA from Osnabrück Universität (Germany) while conducting independent research on a German Chancellor Fellowship from the Alexander von Humboldt Foundation, and bartending at the local kneipe. Her Master’s thesis investigated the ethnological context of immigration and integration of ethnic Germans within eastern and western Germany. She then worked as a consultant for Mercator Partners in Boston, specializing in innovation strategy and mergers/acquisitions for high-tech companies, including the Sprint-Nextel merger. After deciding that corporate American wasn't for her, Noelle decided to pursue veterinary school. While waitressing and wrangling cows, dogs and cats (not at the same time), Noelle took all of the science pre-reqs for vet school and was accepted into the DVM-PhD program at Colorado State University, where she received her doctorate in epidemiology, a USDA NIFA post-doctoral fellowship, and her veterinary degree (large animal medicine). Noelle’s current research program focuses on advancing our understanding of antimicrobial resistance ecology and epidemiology within livestock production systems, and at the livestock-human interface. To achieve this, her lab uses both traditional and nascent methodologies, in collaboration with scientists from diverse fields including veterinary medicine, epidemiology, statistics, animal science, computer science and molecular biology. Noelle also maintains an active outreach program, and strives to conduct applied research in close partnership with stakeholders in agriculture, veterinary medicine and government.

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ColloquiumMap

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VICI Bldg.

VENI Bldg. (1st Floor)

VENI 101 C

VENI 101 B

VENI 101 A

VENI 106 A

VENI 106 B

VENI 107 A

VENI 107 B

Gallery

Restrooms

CVMMarketplace

Vet Med Cafe

Dining Room

Restrooms

Combined Degree Colloquium

Plenary/Student Sessions

Food Serving

Dining

Burroughs Wellcome Fund Workshop

Posters: VENI 3rd FloorRestrooms

VIDI 127

VIDI 121

VIDI 113

VIDI 112

VIDI 102

VIDI 103

VIDI 104

VIDI 105

VIDI 106

VIDI 109

VIDI 115

VIDI 126

VIDI 120

VIDI Bldg.

MAP

Information/Registration

Veterinary & Biomedical Education Complex

(VBEC)

ShuttleBus Stop

Faculty Sessions

PosterLayout

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Posters VENI 1st Floor

(not to scale or proportion)

Patio

Walkway to VICI

Dining Room

Walkway to VIDI

PosterStorage

VENI 106

VENI 107

1129257385

18146274402

19147275403

42170298426

60188316444

43171299427

Posters VENI 3rd Floor

(not to scale or proportion)

Patio

61189317445

70198326454

71199327455

80208336464

100228356484

90218346474

81209337465

91219347475

101229357485

116244372500

117245373501

128256384513

PosterStorage

Walkway to VICI

Balcony

Mark Francis Room

Walkway to VIDI

72’

72’

96’

40’ 40’

64’ 56’

Position these slightly closer to the patio, not centered.They are the only sections where we need both sides.

StudentAbstracts

Posterspresenta+onswillbeonthefirstfloor,encirclingtheclassroomoppositeVENI106A.Wewillstartwithposterposi+on7toprovidesomedistancefromtheregistra+ontable.

Abstract(page)

Poster# Student Abstract(page)

Poster# Student

16 7 DylanAmmons 40 31 AnnieWang

17 8 ElliopChiu 41 32 CourtneyMeason-Smith

18 9 CaitlinDaimon 42 33 JennCossaboon

19 10 KristenDavenport 43 34 ChaseGarcia

20 11 EnriqueDoster 44 35 KaqHorng

21 12 DilaraKiran 45 36 DevanMurphy

22 13 Kris\naCeres 46 37 HarmanpreetPanesar

23 14 FrancesChen 47 38 AyswaryaSundaram

24 15 DavidW.Gludish 48 39 JenniferBloodgood

25 16 EileenTroconisGonzalez 49 40 JacqulineRisalvato

26 17 KieranKoch-Laskowski 50 41 HunterOppler

27 18 EricaLachenauer 51 42 EmilyPope

28 19 AmandaLoehr 52 43 GabrielleRobbins

29 20 KennedyAldrich 53 44 JaclynCarlson

30 21 AshleyPutman 54 45 PierceNathanson

31 22 ZoëWilliams 55 46 BrinkleyRaynor

32 23 SherryBlackmon 56 47 AmandaSamuels

33 24 JamesNichols 57 48 ElinorWillis

34 25 BripanySzafran 58 49 AllisonLudwig

35 26 AmandaKortum 59 50 RosLuethcke

36 27 EmilyMackey 60 51 AlisonCash

37 28 HannahReynolds 61 52 CatharineCowan

38 29 JessicaRomanet 62 53 AmandaKravitz

39 30 CourtneyRousseSparks 63 54 GrantWaldrop

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Poster#7

AnoveleffectofPD-L1immunecheckpointmolecule.

DylanAmmons1,GenHartley1,DavidAckart2,StevenDow1

1AnimalCancerCenter,DepartmentofClinicalSciences,CollegeofVeterinaryMedicineandBiomedicalSciences,ColoradoStateUniversity,Ft.Collins,CO2DepartmentofMicrobiology,ImmunologyandPathology,ColoradoStateUniversity,Ft.Collins,CO

In recent years immune checkpoint blockade has become a promising cancer immunotherapy. Thistherapy aims to block inhibitory receptor-ligand interac\ons between T cells and other cellularcounterparts in the tumormicroenvironment (TME).Bypreven\ng receptor-ligand liga\onTcellsdonot receive inhibitory signals and are able to remain ac\ve. One of the major blocking targets isprogramdeath ligand-1 (PD-1) and the commonlyacceptedbelief is thatblocking the interac\onbytarge\ngtheligand(PD-L1)orreceptor(PD-1)wouldhavethesameresult.Hereweshowthatthismaynotbe the case for PD-1/PD-L1blockadeandprovidedatawhich indicatePD-L1blocking an\bodies(αPD-L1mAb)areabletoac\vatemurinebone-marrowderivedmacrophages.TreatmentwithαPD-L1mAb induces morphologic and phenotypic changes which support the no\on that the treatedmacrophagesbecomeac\vatedandproliferate.Wetheniden\fiedthatthechangesaremediatedviamTOR/AKT signaling axis. With evidence that signaling is mTOR mediated, macrophage metabolicchanges were examined via extracellular flux analysis to beper understand the func\onal changesinducedbyαPD-L1mAbtreatment.Dataobtainedthoughfluxanalysisindicatedthattreatmentcausesmacrophagestobecomemoremetabolicallyac\ve.Throughfluxanalysiswenotedthattheresponsetotreatmentisalteredbythepresenceorabsenceofthemacrophagedifferen\a\onfactor,M-CSF.TheM-CSF/PD-L1 interac\onwas thenexamined through signal transduc\onandflux analysis to furtherelucidate the effect. Overall, this work provides valuable insight into addi\onal func\ons of αPD-L1mAbtreatmentwhichcouldcontributetodifferentinvivoefficacies.SupportedbytheShipleyFounda\onandNIHgraduatestudents\pend

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Poster#8

Fromfieldtolab:lackofendogenousfelineleukemiavirusmayleavepumasvulnerabletoFeLVinfec'on

ElliopChiu,MarkCunningham,LaraCusack,MelodyRoelke,SueVandeWoude

DepartmentofMicobiology,ColoradoStateUniversity,FortCollins,CO(Chiu,VandeWoude)FloridaFishandWildlifeConserva\onCommission,FL(Cunningham,Cusack)Na\onalIns\tutesofHealth,MD(Roelke)

Felineleukemiavirus(FeLV)regularlyinfectsdomes\ccatsandhasbeenfrequentlydocumentedtospillovertomanywildfelidspecieswithdevasta\ngclinicaloutcomes.WhilecatsharboranearcompleteendogenizedFeLV(enFeLV)resemblingtheinfec\ous,horizontallytransmipedvirus,manyotherfelidspecies,lackenFeLV.EnFeLVrecombina\onisresponsibleforrecombinantoncogenicFeLVvariantssuchasFeLV-B;itisalsobelievedtoblockhorizontaltransmissionandpar\allyprotectagainstFeLVdisease.WethushypothesizethatenFeLVplaysaroleinintrinsicFeLVrestric\onindomes\ccatsandlackofenFeLVcorrelateswithmorevirulentdiseaseinotherfelids.Ourstudieshavedocumentedthefirstdetec\onofaFeLV-Binanon-domes\cfelid,andhavedemonstratedmul\plecrossspeciestransmissionsinfreerangingFloridapanthers(Pumaconcolorcoryi).Wemeasuredproviralload,viralreplica\on,andviralan\genproduc\onfollowingFeLVinfec\onofdomes\ccatandpumafibroblastsandperipheralbloodmononuclearcellstoevaluatethecapacityofFeLVtoreplicateindifferentfelidcells.Domes\ccatcellsdisplayedanega\vecorrela\onbetweenFeLVreplica\onandenFeLVcopynumber,dependentuponenFeLVLTRversusenvsegments.Interes\ngly,pumacellssupportedsignificantlygreaterviralreplica\on.Differen\alexpressionofenFeLVinvarious\ssuesindicatesthatlymphoid\ssues,theprimaryreplica\onsiteofFeLV,expressenFeLVgreatertranscrip\onthanother\ssues.Insum,theFeLVsystempresentsanopportunitytoexamineendogenous-exogenousretroviralinterac\onsfromlabbenchtonaturalpopula\ons,providinginsightintoendogenousretrovirusbiologyinhumans.

ResearchGrantsNSFEID1413925Winnnewfelineinves\gatorawardW18-018

StudentSupportNIHF30OD0827386NIHT32OD012201CSUDVM/PhDprogram

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Poster#9

β-endorphinfromproopiomelanocor'nneuronscanmediateac'vity-basedanorexiainmice

CaitlinMDaimon,Chris\naSDennison,ShaneTHentges

DepartmentofBiomedicalSciences,CollegeofVeterinaryMedicineandBiomedicalSciences,ColoradoStateUniversity,FortCollins,CO.

Proopiomelanocor\n(POMC)neuronsinthearcuatenucleusofthehypothalamuspotentlyinhibitfoodintakeandtheirover-ac\va\onmaycontributetothedevelopmentofanorexia.Ac\vity-basedanorexia(ABA)isacommonlyusedrodentmodelofanorexia(reducedfeeding)inwhich\medfoodpresenta\onpairedwithavailabilityofarunningwheelresultsinreducedfoodintake,increasedwheelrunningac\vityandbodyweightloss.However,itisunknownwhetherinhibi\ngPOMCneuronsandthesubsequentreleaseoftheirpep\deproductswouldbesufficienttoreducethedevelopmentofABA.Toexaminethepossibilitythatinhibi\ngPOMCneuronscouldlessenthedevelopmentofABA,chemogene\c(DesignerReceptorsExclusivelyAc\vatedbyDesignerDrugs;DREADD)technologywasusedtoselec\velyinhibitPOMCneurons.Consistentwithourhypothesis,inhibi\ngPOMCneuronsledtoasignificantdecreaseinfoodan\cipatoryac\vity(enhancedrunningbeforefoodpresenta\on),ahallmarkoftheABAmodel.Todetermineifthedevelopmentoffoodan\cipatorybehaviorinmicerequiresthereleaseofthePOMCpep\deβ-endorphin,wetestedhowtheadministra\onofanantagonistofthereceptorswhichβ-endorphinactsonaffectsthedevelopmentofABA.Wefoundasignificantdecreaseinfoodan\cipatoryac\vitywhentheantagonistnaloxonewasadministered.BodyweightlosswaslessseverewhenPOMCneuronswereinhibitedandalsowhennaloxonewasadministeredcomparedtosaline-treatedanimals.Takentogether,theresultssuggestthatinhibi\ngPOMCneuronsresultsinalessseverepresenta\onofABAandthatthisismediated,atleastinpart,byβ-endorphin.

Researchgrant:R01DK078749toSTH

Studentsupport:F30DK117530toCMD

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Poster#10

Prionsheddinginsalivaexplainsthehorizontaltransmissionofchronicwas'ngdisease

KristenA.Davenport1,ClareE.Hoover1,BripanyA.Mosher2,BrianM.Brost2,DavinM.Henderson1,NathanielD.Denkers1,CandaceK.Mathiason1,EdwardA.Hoover1

1DepartmentofMicrobiology,ImmunologyandPathology,CollegeofVeterinaryMedicineandBiomedicalSciences,ColoradoStateUniversity,FortCollins,CO2DepartmentofFish,WildlifeandConserva\onBiology,CollegeofNaturalResources,ColoradoStateUniversity,FortCollins,CO

Chronicwas\ngdisease(CWD),aneurodegenera\vediseaseofcervids,isuniqueamongpriondiseasesinitsefficienthorizontaltransmissioninwildpopula\ons.CWDisspreadingacrossNorthAmericaandhasreachedAsiaand,recently,Scandinavia.Prionshavebeendetectedin\ssuesandexcretaofCWD-infectedcervids,butthecourseprionstakefromini\alinfec\ontoexcre\onandthemagnitudeandfrequencyofprionsheddingremainunknown.Toanswertheseques\ons,we:(1)usedinvitroamplifica\onmethodstocomparethedistribu\onofprionsinlymphoidandgastrointes\nal\ssuesofdeerearlyandlateindisease,andcorrelatedpriondistribu\onwithprionsheddinginsalivaandneuroinvasion;(2)usedanecologymodelingapproachtodemonstratethatthelikelihoodofprionsheddinginsalivawas2.77\meshigherindeerinoculatedwithsalivavs.brain;(3)demonstratedthatdeersalivacommonlycontainedaninhibitorofthereal-\me,quaking-inducedconversion(RT-QuIC)assayandcharacterizedtheinhibitorasamemberofthemucinfamily;and(4)developedanalternateprotocoltobypasstheinhibitorandimprovedetec\onofprionsinsaliva.Takentogether,ourdatademonstratethatprionsareshedinsalivaearlierandmorefrequentlythanpreviouslyexpected,andsuggestthatsalivaplaysanimportantroleinthelargerstoryoffacilehorizontalspreadofCWDamongcervids.

ResearchSupport:NIHN01AI25491,NIHR01NS047433,andNIHR01NS061902

StudentSupport:NIHF30OD021442

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Poster#11

An'microbialuseinbeeffeedlots;effectsonmicrobiomeandresistomedynamics

Authors:E.Doster,J.K.Parker,C.A.Anderson,S.M.Lakin,N.R.Noyes,M.Weinroth,C.W.Booker,S.J.Hannon,S.P.Gow,T.A.McAllister,K.E.Belk,P.S.Morley.

Affilia'ons:DepartmentofClinicalSciences(Parker,Anderson,Morley),AnimalSciences(Weinroth,Belk),andtheDepartmentofMicrobiology,ImmunologyandPathology(Doster,Lakin),ColoradoStateUniversity,FortCollins,Colorado;DepartmentofVeterinaryPopula\onMedicine,UniversityofMinnesota,St.Paul,Minnesota(Noyes);FeedlotHealthManagementServices,Ltd.,Okotoks,AlbertaT1S2A2,Canada(Booker,Hannon);CentreforFood-borne,EnvironmentalZoono\cInfec\ousDiseases,PublicHealthAgencyofCanada,UniversityofSaskatoon,Saskatchewan,Canada.(Gow);AgricultureandAgri-FoodCanadaResearchCentre,Lethbridge,AB,Canada.(McAllister)

AbstractContent:Theincreaseofan\microbialresistance(AMR)inpathogensisaglobalpublichealthconcernandiscommonlyhypothesizedtobe“driven”byan\microbialuse(AMU)inhealthcareandlivestockproduc\on.Therefore,itisimportanttounderstandhowAMUprac\cesinbeeffeedlotopera\onsimpactAMRdynamicsinfecalbacteriathatcouldspreadtothesurroundingenvironment.Tradi\onally,AMRresearchusesaerobicculturetostudyjustafewbacterialspeciesfromacomplexbacterialcommunity(microbiome)andresultscandifferdependingonthespeciesunderstudy.Fortunately,advancementsinhigh-throughputsequencingcanbeusedtoprovideaholis\cperspec\veintoAMRecologybysequencingDNAfromtheen\remicrobiome,includingthe“profile”ofresistancegenes(resistome).InthisstudyweemploymetagenomicsequencingtocharacterizetheeffectofAMUonthemicrobiomeandresistomeinfecescollectedduringapreviouslypublished3-yearlongitudinalstudyofCanadianbeeffeedlotopera\ons.Pensofcaplewererandomlyselectedforinclusionintothestudyandpooledfecalsampleswerecollectedfromthepenfloorwhencaplearrivedtothefeedlotandataseconddateduringthefeedingperiod.AllAMU,includingparenteraltreatmentsandin-feedexposures,wasrecordedandstandardizedusinganimaldefineddailydose(ADD).PenlevelAMUwascalculatedasthesumofADDsforallcaplehousedinapen.Ourpreliminaryresultscharacterizethemicrobiomeandresistomeecologyinbeeffeedlotopera\ons;further,weareabletomakeuniquecomparisonsofresultsinves\ga\ngtheimpactofAMUonAMRproducedbytradi\onalaerobicculturemethodscomparedtothemoderntoolofmetagenomicsequencing.

ResearchGrant:USDANIFAgrant#215-68003-2304

StudentSupport:NIH-T32PredoctoralScholarProgram(ColoradoStateUniversity)

� 20

Poster#12

‘Ironingout’Mycobacteriumtuberculosis-mediatedchangesinmacrophagemetabolism

DilaraKiran1,AndresObregon-Henao1,DavidAckart1,MichioKuruso2,BranchMoody3,BrendanPodell1,RandallBasaraba1.

1. DepartmentofMicrobiology,Immunology,Pathology;CollegeofVeterinaryMedicineandBiomedicalSciences;ColoradoStateUniversity;FortCollins,CO

2. CollegeofPharmacy;UniversityofTennesseeHealthScienceCenter;Memphis,TN3. DivisionofRheumatology,Immunology,andAllergy;BrighamandWomen’sHospital;Boston,

MA

Lactate,theproductofglycolysis,isaknownsubstrateforoxida\vemetabolismandcontributestoimmunosuppression.DuringMycobacteriumtuberculosis(Mtb)infec\on,serumlactatelevelsareelevatedandlactateconcentra\onswithinthelunggranulomaincrease.WehaveshownthatguineapigsinfectedwithMtbdemonstrateincreasedplasmalactatelevelswhencomparedtouninfectedanimals,andthattherapeu\cinterven\oncanlowertheselevels.Despitethisknowledge,thefunc\onoflactateandmechanismsbywhichitaccumulatesduringMtbinfec\onareunclear.Hypoxiainduciblefactor-1α(HIF-1α)upregulatesglycolysisandincreaseslactateproduc\on.HIF-1αdegrada\onrequiresironcofactorsandironchela\onhasbeenshowntoac\vateHIF-1αbyinhibi\ngitsdegrada\on.Wehypothesizethattheiron-chela\ngsiderophoreproducedbyMtb,mycobac\n,isresponsiblefordrivingHIF-1αac\va\onduringearlyinfec\on,facilita\ngametabolicshi}fromoxida\vemetabolismtoglycolysisandcausinglactateaccumula\on.Wehavedemonstratedthatguineapigbonemarrowderivedmacrophagestreatedwithmycobac\nexhibitincreasedHIF-1αproteinlevelsinaconcentra\on-dependentmanner.Mycobac\nknock-outstrainsofMtbwillbeusedtodeterminewhethermycobac\n-mediated,hypoxia-independentHIF-1αac\va\ondrivesametabolicshi}toglycolysisandsubsequentlactateaccumula\oninvitroandinvivo.Wewilldeterminewhetherthismechanismleadingtoincreasedlactateproduc\onaltersimmunecellfunc\onandhowaccumulatedlactateisu\lizedwithinthegranulomatodrivetheforma\onofanMtbsurvivalnicheandpreventefficientMtbclearance.

ResearchGrants:1U19AI111224-011R21AI1072541R01AI106733

StudentSupport:CSUCVMBSPredoctoralT32(July2017-July2018)1F30OD024647-01A1(awarded07/03/2018)

� 21

Poster#13

EnvironmentalpersistenceofMAPasabarriertoJohne’sdiseaseelimina'on

Kris\naCeres,MohammadAbdullahAl-Mamun,YrjöGröhn

Popula\onMedicineandDiagnos\cSciences,CornellUniversityCollegeofVeterinaryMedicine,Ithaca,NY(Ceres,Gröhn);DepartmentofEpidemiologyofMicrobialDiseases,YaleUniversity,NewHaven,CT(Al-Mamun)

Johne’sdiseaseispervasiveondairyfarmsintheUnitedStatesandisnotoriouslydifficulttocontrol.OnesuspectedreasonforthedifficultyinmanagingJohne’sdiseaseistheabilityforMycobacteriumaviumssp.paratuberculosis(MAP),thecausa\veagent,topersistintheenvironment.AnimalsbecomeinfectedwithMAPbyinges\ngcontaminatedmaterialintheirenvironment,andonceinfectedcanshedlargequan\\esofMAPintheirfeces.WithfecalsheddingcoupledtotheabilityofMAPtopersistintheenvironment,dairyfarmersmaybeunabletoridtheirherdofJohne’sdiseasewithoutintensefocusonenvironmentalmanagement.Althoughitiswelldocumentedthatenvironmentalcontamina\onisanimportantfactorinMAPtransmission,fewsimula\onmodelsincludeanenvironmentalcomponent,andnoagent-basedmodelwithexplicitenvironmentaltransmissionexists.Wedevelopedanagent-basedmodelofJohne’sdiseaseinaUSdairyfarmwithexplicitenvironmentalMAPtransmission.Individualcows,groupedbyageandproduc\oncharacteris\cs,couldbecomeinfectedthroughexposuretoMAPintheirsimulatedenvironment.InfectedanimalscouldcontaminatetheirenvironmentbysheddingMAPquan\\espropor\onaltotheamountofmanureproducedandtheirinfec\onstage.Usingthismodel,determinedifherdlevelMAPelimina\onwaspossiblethroughintensiveenvironmentalmanagement.WealsodeterminedifathresholdofenvironmentalMAPcontamina\onexiststhatpreventselimina\on.WefoundthatMAPelimina\onispossiblewithvigorouscleaningalone,butthelevelofhygienenecessaryforelimina\onislikelyimpossibletoachieveinatrueherd.

ResearchGrant:Na\onalIns\tuteofFoodandAgricultureoftheUnitedStatesDepartmentofAgriculturethroughNIFAAwardNo.2014-67015-2240

Studentsupport:sameasresearchgrant

� 22

Poster#14

Genomeedi'ngattheAF-associatedPitx2Locus:aroleforthelncRNAPlayrrinCardiacArrhythmias

FrancesL.Chen,EvaM.Oxford,ErinKDaugherity,JohnP.Leach,JamesF.Mar\nandNataszaA.Kurpios

DepartmentofMolecularMedicine(Chen,Oxford,Kurpios),DepartmentofBiomedicalSciences,CenterforAnimalResourcesandEduca\on(Daugherity),CollegeofVeterinaryMedicine,CornellUniversity;DepartmentofMolecularPhysiologyandBiophysics(Leach,Mar\n),BaylorCollegeofMedicine

AtrialFibrilla\on(AF)isthemostcommonarrhythmiaworldwideinhumans,withseriousimplica\onssuchasstroke,cardiacarrest,anddeath.ThemostsignificantlyassociatedAFrisklocimaptovariantsinanoncoding,puta\veregulatorygenedesertupstreamofthePitx2locus.Indeed,lossofPitx2inmiceandhumansisassociatedwithcongenitalcardiacdefects,increasedsuscep\bilitytoatrialfibrilla\on(AF),developmentofbilateralsinoatrialnodes(SAN),andsinusnodedysfunc\on(SND).However,thegene\cmechanismsbywhichPitx2anditsassociatedcis-regulatoryelementsatthelocuscontributetothedevelopmentofAFremainunclear.

PreviouslywediscoveredPlayrr,aconservedenhancer-associatedlongnoncodingRNA(lncRNA),arisingfromthePitx2locusgenedesert.Toinves\gatetheroleofPlayrrinregula\ngPitx2,weusedCRISPR/Cas9genomeedi\nginmicetotargetthePlayrrRNAtranscriptwhileleavingitsassociatedenhancerelementintact(PlayrrEx1sj).Byadap\nganawakesurfaceECGdevice(AliveCor)foruseinmice,wedetectedcardiacarrhythmiasinPlayrrEx1sjmutantsandvalidatedtheseresultswithtelemetryECG.WedemonstratethatadultPlayrrEx1sjmutantmiceexhibitbradycardiaandirregularR-Rintervalsthatareindica\veofsinusnodedysfunc\on(SND),abradyarrhythmiaandriskfactorforthedevelopmentofAF.Finally,programmeds\mula\onrevealsthatPlayrrEx1sjmutantsarepredisposedtopacing-inducedAF,strikinglysimilartoPitx2loss-of-func\onmutantheterozygousmice.OurdatasuggeststhatPlayrrmodulatesPitx2genedosageintheheartleadingtoconduc\onabnormali\esandpredisposi\ontoimportantcardiacarrhythmias.

StudentSupport:NIHF30OD021454-03

� 23

Poster#15

NovelcellulartoolstostudyHIVreplica'onin'ssuereservoirsandimprovestandardviraloutgrowthassaysDavidW.Gludish,SaikatBoliar,HenryC.Mwandumba,KondwaniC.Jambo,andDavidG.RussellMicrobiologyandImmunology,CornellVeterinaryMedicine,Ithaca,NY.(Gludish,Boliar,Russell)Malawi-Liverpool-WellcomeTrustClinicalResearchProgramme,UniversityofMalawi,Blantyre,Malawi.(Mwandumba,Jambo)DepartmentofClinicalSciences,LiverpoolSchoolofTropicalMedicine,Liverpool,UK.(Mwandumba,Jambo)Humanimmunodeficiencyvirus(HIV)remainsadominantglobalhealthcrisis,affec\ngtensofmillionsofpeopleworldwide.Viralreservoirsareestablishedearlyduringacuteinfec\on,anddespiteyearsoffullysuppressivean\retroviraltherapy(ART),theypersistforthelife\meofthepa\entinanunknowndiversityofcells.OurpriorworkdemonstratedthepresenceofHIVmRNA in\ssue-residentalveolarmacrophages in the lungs ofMalawian adults inMalawi, Africa, sugges\ng these cellsmay be viralreservoirs. Aided by cell-level HIV readouts,we have recovered infec\ousHIV frombronchoalveolarlavageandarestudyingthehumantranscriptsandviraladapta\onsthatfacilitatethispersistence.Newreportercelllineswehavedevelopedhaveshownthatstandardprotocolsofviraloutgrowthlikelymissmany replica\on competent viruseswithin the context of gold-standard assays, underes\ma\ng thetrueHIVburdenduringHIVorSIVcureortreatmentinterrup\ontrials.OurfindingssuggestthatrareHIV proviruses within \ssue reservoirs may be poorly adapted to replicate in standardized,homogeneous outgrowth assays. Furthermore, comparing human monoctye-derived macrophageswithothercellsinthe\ssue-residentmacrophagelineage,wehaveuncoveredopportuni\estopursuenovel restric\on factors that may affect HIV persistence in vivo. Our overarching objec\ve is tocontributetonewHIVtherapiestargetedtospecific\ssuereservoirs.

ResearchGrants:NIAID(AI118582),Russell;NHLBI(HL100928),Russell;WellcomeTrust(088696/Z/09/Z),Mwandumba;BillandMelindaGatesFounda\on(OPP1125279),Mwandumba;NIHOD(T32OD011182),Gludish

StudentSupport:NIAID(AI118582),Russell;NIHOD(T32OD011182),Gludish

� 24

Poster#16

Dorsalrapheserotoninneuronsandemo'onalgain

EileenL.Troconis,ChangwooSeo,AkashGuru,RyanJ.Post,Yi-YunHo,DavidA.Bulkin,AndrewK.Recknagel,MelissaR.Warden

DepartmentofNeurobiologyandBehavior,CornellUniversity,Ithaca,NewYork

Serotonin(5-HT),awidely-projec\ngneuromodulatorysystem,hasbeenimplicatedinavarietyofbehaviorsandbrainstates.Thedevelopmentofatheore\calmodelof5-HTfunc\onthataccountsforthisdiversityhaschallengedthefield.Asaresult,themechanismbywhich5-HTlevelsaffectemo\onalbrainstatesandbehaviorremainsunclear,despitethecommonuseofselec\veserotoninreuptakeinhibitors(SSRIs)inthetreatmentofdepressionandanxietydisorders.Wehypothesizethat5-HTamplifiescurrentemo\onalstates,intensifyingtheposi\vevalueofrewardingcondi\ons,andthenega\vevalueofaversivecondi\ons.Here,wedescribetwoexperimentstotestthishypothesisusingchoiceasabehavioralread-out.Thefirstexperimentisacondi\onedplacepreferenceparadigm.Miceshowslightpreferencefororavoidanceofplaceswithmildlyrewardingoraversives\muli,respec\vely.Wepredictthatcondi\oningwithoptogene\cs\mula\onofdorsalraphe5-HTneuronswillincreasepreferencefororavoidanceoftheseplacesaccordingly.Thesecondexperimentisanoperantchambertaskwheremicechoosebetweenperforminganac\ononthele}ortherighttocollectaprobabilis\creward.Wepredictthat5-HTneurons\mula\onuponrewardretrievaloromissionononesidewillshi}thepreferencetowardorawayfromthatside,respec\vely.Currentworkisfocusedontaskop\miza\onandbehavioralcharacteriza\on.Theresultsoftheseexperimentswilldeterminehows\mula\onofdorsalraphe5-HTneuronsaffectsrewardvalua\onandchoice,whichwillshedlightontheroleofthissysteminemo\onalgainandstate-dependentbehavioralregula\on.

ResearchGrants:NIHDirector’sNewInnovatorAward,RobertsonNeuroscienceInves\gatorAwardfromtheNewYorkStemCellFounda\on,SloanResearchFellowship,WhitehallResearchGrant,NARSADYoungInves\gatorAwardStudentSupport:CornellUniversity(MelissaR.Warden)

� 25

Poster#17

InduciblehGlp-1rknockoutinthemousehypothalamuspromotesfeedingandbodyweightgain

KieranKoch-Laskowski,DarlineGaribay,KarolinaZaborska,BethanyCummings

DepartmentofBiomedicalSciences,CollegeofVeterinaryMedicine,CornellUniversity,Ithaca,NewYork

Obesityanditsassociatedco-morbidi\es,suchastypeIIdiabetesmellitus,representwidespreadandcostlypublichealthepidemics.Thecurrentlackofeffec\ve,long-las\ngan\-obesitytreatmentsnecessitatesabeperunderstandingoftheneurobiologicalsystemsthatregulatefeedingbehaviorandenergybalance.Duetoitsestablishedroleinreducingfoodintakeandpromo\ngglycemichomeostasis,theglucagon-likepep\de-1(GLP-1)systemhasbeenapromisingtargetforpharmaceu\calinterven\ons.However,themechanismsthroughwhichthisincre\nhormoneactsinthecentralnervoussystemremainunclear.Condi\onalknockoutstudiesofferaneleganttechniquetoinves\gatetheeffectsofendogenousreceptorsignalinginatargeted\ssuewithoutcompromisingnormalontogene\cdevelopment.UsingtheCre/loxPsystem,wegeneratedaninducible,site-specificknockoutmodeloftheGLP-1receptor(GLP-1R)inthemousehypothalamus.AdultmaleC57BL/6miceexpressingfloxedhumanGlp-1r(hGlp-1r)weremaintainedona60%highfatdiettoachievediet-inducedobesity.Subsequently,micewerestereotaxicallyinjectedwithaCre-expressingorcontroladeno-associatedvirus(AAV-Cre/AAV-Ctrl).ViralknockoutofhypothalamichGlp-1rcausedincreasedfoodintakeandbodyweightgainthroughoutthe14dayspost-injec\on(Final24hfoodintake:AAV-Ctrl=3.06±2.16g,AAV-Cre=4.30±3.04g,p=0.02;Finalbodyweight:AAV-Ctrl=27.20±0.10g,AAV-Cre=32.89±1.04g,p=0.06).Altogether,thesedatademonstratethatendogenousGLP-1Rsignalinginthemousehypothalamusisnecessarytoregulateenergybalance.

ResearchGrant:USDepartmentofDefenseW81XWH-18-1-0206StudentSupport:CornellUniversityCollegeofVeterinaryMedicineVeterinaryInves\gatorProgram

� 26

Poster#18

Inves'ga'ngtheeffectofp53lossonfolatemetabolisminthedevelopmentofneuraltubedefects

EricaLachenauer,ElenaKamynina,MarthaField,andPatrickJ.Stover

BiologicalandBiomedicalSciences(Lachenauer),DepartmentofNutri\onalSciences(Kamynina,Field),CornellUniversity,Ithaca,NY;AgricultureandLifeSciences(Stover)TexasA&MUniversity,CollegeSta\on,TX

Neural tubedefects (NTDs)arebirthdefects thatresult inhernia\onandexposureofnervous\ssueduring embryogenesiswhen the neural tube fails to close. Folate deficiency causes failure of neuraltubeclosureanditises\matedthat70%ofallNTDsarefolateresponsive.However,themechanismofthisrescueeffectremainstobeelucidated.Thetumorsuppressorproteinp53playsanimportantrolein development and both increased and decreased expression and/or func\on can lead to NTDs inmousemodels.Studiesinvitrodemonstrateinterac\onsamongp53andfolateone-carbonmetabolismpathways, specifically the de novo thymidylate (dTMP) biosynthesis pathway. Mouse models withimpaired de novo dTMP synthesis have increased rates of NTDs that are responsive to folatesupplementa\on. The aim of this project was to determine if folate supplementa\on could rescuep53-/- induced NTDs. Interes\ngly, p53-/- mouse embryonic fibroblasts have higher rates of folate-dependentdenovodTMPsynthesis,purinebiosynthesis,uracilaccumula\oninDNA,andprolifera\on.Theseresultssuggestthatlossofp53causesincreasedgrowthandthusincreasednucleo\desynthesistoaccommodate,howevernotat levels thataresufficient toameliorateuracilaccumula\on inDNA.Folatesupplementa\onisalsonotadequatetopreventp53-/-NTDincidence.

ResearchFunding:NIHNa\onalIns\tuteofChildHealthandHumanDevelopmentR01HD059120

StudentFunding:NIHNa\onalIns\tuteofChildHealthandHumanDevelopmentF30HD093288

� 27

Poster#19

Mammarystem-likecellsfrommammarycancerresistantandsuscep'blespeciesdifferinresponsetoUV

AmandaLoehr,GatRauner,MelissaLedet,GerlindeVandeWalle

DepartmentofMicrobiologyandImmunology,BakerIns\tuteforAnimalHealth,CollegeofVeterinaryMedicine,CornellUniversity,Ithaca,NY

Differentspeciesvarygreatlyintheirmammarycancerincidence.Likehumans,mammarytumorsareamongthemostcommonneoplasmsinintactfemaledogsandcats.Conversely,cows,mares,andsowsrarelydevelopmammarytumors.Mammarystemcells(MaSC)resideintheadultmammaryglandswheretheymaintainandregeneratethe\ssue.Astargetsformalignanttransforma\on,MaSCsmayalsobecancercellsoforigin.Mammosphere-derivedepithelialcells(MDEC)areprimarymammarycellswithstem-likeproper\esthatcanbeisolatedfromdiversespeciesandusedforcompara\vestudies.WeusedMDECtocomparesensi\vitytoDNAdamagebetweenmammarycancerresistantandsuscep\blespecies.PreviousworkshowedthatMDECfromresistantspeciesaremoregrowth-sensi\vetoDNAdamage(inducedbyDMBAorUV)thanMDECfromsuscep\blespecies.RNAsequencingandqPCRanalysesrevealedthathorseMDECstronglyupregulatep21anddownregulateRunx1T1inresponsetoDMBAorUV,whereasdogMDECdonot.p21promotescellcyclearrestinresponsetovariousstresses,includingDNAdamage.Thefunc\onofRunx1T1inthecontextofDNAdamageislessknown.UsingqPCR,p21andRunx1T1expressionwasanalyzedfollowingUVexposureinMDECfromaddi\onalspeciesthataremammarycancersuscep\ble(humanandcat)orresistant(cowandpig).Wedidnotobserveanexpressionpapernofthesegenesthatisuniquetoresistantorsuscep\blespecies.Upcomingexperimentswillbeaimedatiden\fyingthemechanismbywhichp21isupregulated,thetemporalpapernofp21expressionfollowingUVexposureaswellasinves\ga\ngtheroleofp21intheUVsensi\vityofMDECfrommammarycancer-resistantspecies.

ResearchGrant:NoneStudentSupport:NIHT35TrainingGrantOD010941-09

� 28

Poster#20

Effectofdietonglycogenreple'oninThoroughbredhorsesagerexercise

KennedyAldrich1,JoePagan2andStephanieValberg1

1CollegeofVeterinaryMedicine,MichiganStateUniversity,EastLansing,MI,2KentuckyEquineResearch,Versailles,KY.

Whenmuscleglycogenstoresinhorsesaredepleteda}erexercise,re-synthesisofglycogenproceedsatarate2-3\messlowerthanthatofothermammals.Thereasonforslowreple\onisunknown.Humansandothermammalscanspeedglycogenreplenishmentbyconsumingcarbohydratesa}erexercise,however,similardietarymanipula\onstoenhancereple\onratesinhorseshasmetwithliplesuccess.Wehypothesizethattranscriptomic(RNAseq)andproteomicanalysisofequinemuscleduringglycogendeple\onandreple\onwillrevealtheunderlyingmechanismresponsibleforslowglycogenreple\oninhorses.Acrossoverglycogendeple\onandreple\ontrialusingisocalorichighstarch(HS)andlowstarch-highfat(LS)dietswasperformedinpartnershipwithKentuckyEquineResearch.HSandLSdietswerefedtotrainedThoroughbredhorsesfor3weekswhichwasfollowedby3daysofintense,glycogendeple\ngexerciseand3daysofreple\on.Percutaneousgluteusmediusmusclebiopsieswereobtainedbeforeanda}erexerciseandduringreple\on.Muscleglycogenconcentra\onsweremeasuredfluorometricallyasglucoseresidues.Muscleglycogenwasdepleted67%(SD17%)followingexerciseonHSand70%(SD8%)followingLSdiets.OnDay3ofreple\on,muscleglycogenwas94%(SD14%)repletedonHS,whichwassignificantlygreaterthan63%(SD20%)reple\onforLS.Analysisofaltera\onsintheskeletalmuscletranscriptomeandproteomeduringdeple\onandreple\onisunderway.Elucida\ngtheunderlyingmechanismlimi\ngglycogenreple\onrateinhorsesmayleadtonutri\onalmethodstoimproveperformance.ResearchGrant:MichiganAllianceforAnimalAgricultureandKentuckyEquineResearch.StudentSupport:BoehringerIngelheimandtheMichiganStateUniversitygraduateschool.

� 29

Poster#21

Oxylipidprofilesofdairycahlevarythroughoutthetransi'onintoearlymammaryglandinvolu'on

AshleyPutman,JenniferBrown,JeffGandy,LorraineSordillo

LargeAnimalClinicalSciences,CollegeofVeterinaryMedicine,MichiganStateUniversity,EastLansing,MI

Successfullacta\oninmul\parousdairycaplereliesonawell-manageddryperiodthatallowsthemammaryglandtoremodelandregeneratebetweenlacta\ons.Oxylipidsarepotentinflammatorymediatorsthatarecapableofregula\ngallaspectsofinflamma\on.Althoughanoxylipidprofilehasbeendocumentedforperiparturientandlacta\ngcaple,lipleworkhasbeendonetodefinetheprofileofcowsintheearlydryperiod.Therefore,ourgroupaimedtocharacterizetheoxylipidprofileinhealthycowsduringthetransi\onintoearlymammaryglandinvolu\on.Plasmasamplesfrom10healthyHolsteindairycowswerecollectedviacoccygealvenipunctureatD-6,D0,D+1,D+2,D+6,andD+12rela\vetodry-offdate.Liquidchromatography-massspectrometry(LC-MS)wasu\lizedtoquan\fyselectmonounsaturatedfapyacids(MUFA),polyunsaturatedfapyacids(PUFA),andsaturatedfapyacidswhileliquidchromatography-tandemmassspectrometry(LC-MS/MS)wasusedtoquan\fyoxylipids.Theresultsofthisstudyrevealedauniqueprofileofpro-andan\-inflammatoryoxylipidsthroughoutthetransi\onintothedryperiod.Manycompoundsreachedhighestconcentra\onsofthestudyeitheratD+1orD+12,whichmayberelatedtothephysiologicalprocessesthatareassociatedwiththetransi\onfromalacta\ngtonon-lacta\ngstate.Thecharacteriza\onofthisprofileallowsforabasicunderstandingonhowtheoxylipidspresentduringearlyinvolu\onmayimpactthehealthandproduc\vityofdairycows.

USDANIFA(2014-68004-21972and2017-67015-26676),MeadowBrookEndowmentfromtheMa\ldaR.WilsonFund,andMichiganAllianceforAnimalAgriculture.MichiganStateUniversityCollegeofVeterinaryMedicineGraduateSchool

� 30

Poster#22

ProteomicprofilingofWarmbloodhorseswithMyofibrillarMyopathy

ZoëWilliams,SudeepPerumbakkam,MelissaSchop,StephanieValbergLargeAnimalClinicalSciences,CollegeofVeterinaryMedicine,MichiganStateUniversity,EastLansing,MI

Myofibrillarmyopathies(MFM)inhumansarecausedbymuta\onsingenesthatencodesarcomereZ-discproteinsandpresentwithprogressiveskeletalmuscleweakness.MFMhasrecentlybeeniden\fiedinWarmbloodhorses(WB)withexerciseintolerancebasedondesminimmunohistochemistryandZ-discandmyofibrillardisrup\oninmusclebiopsies.WehypothesizedthatspecificZ-discproteinsiden\fiedthroughproteomicanalysiswouldbedifferen\allyexpressedinMFMWBandthattheirencodinggeneswouldbecandidategenesforequineMFM.Theobjec\veofthisstudywastocompareproteomicprofilesof5MFMWBand4healthycontrolWB.Proteinwasextractedfromsnapfrozenglutealmuscle,digestedintrypsinandlabeledwithisobarictags(iTRAQ10-plex)formul\plexedMS/MSquan\ta\veanalysis.Proteinswereiden\fiedwiththeEquuscaballuscomplementofUniProtKB

andsignificancewasdeterminedbyaMann-WhitneytestwithPvaluesadjustedformul\pletes\ngusingaBonferronicorrec\on.1532proteinswereiden\fiedand105weredifferen\allyexpressedinMFMvs.controls(P<0.00003).GeneOntology(GO)enrichmentanalysisforcellularprocessesiden\fied22sarcomereproteins(P=0.0005),15I-bandproteins(P=0.026),13Z-discproteins(P=0.041),and14oxidoreductasemitochondrialproteins(P=0.047)thatwereoverrepresentedinMFMWB(FDR<0.05).ProteinsencodedbygenesknowntocauseMFMinhumanswereamongstsignificantlyupregulatedproteinsandrepresentcandidategenesforfurtherinves\ga\onofMFMinhorses.Withtheirlargemusclemassandselec\onforathle\cperformance,WBhorsescouldserveasauniquemodelforhumanMFM.

ResearchGrant:MaryAnneMcPhailEndowmentStudentSupport:AVMF2ndOpportunityResearchScholarship,MSUCMIBGraduateGroup

� 31

Poster#23

PathogenicityofemerginginfluenzaDvirusandswineinfluenzaAvirusco-infec'onindomes'cpigs

SherryBlackmon,XiaojianZhang,LiyuanLiu,AliciaK.Olivier,MinhuiGuan,MarkCrenshaw,ShengfaLiao,WilliamEpperson,andXiu-FengWan

DepartmentofBasicSciences,CollegeofVetMed(Blackmon,Zhang,Liu,Guan,Wan),DepartmentofPopula\onandPathobiologyMedicine,CollegeofVetMed(Olivier,Epperson),DepartmentofAnimalandDairyScience,CollegeofAgricultureandLifeSciences(Crenshaw,Liao),MississippiStateUniversity,MississippiState,MS

Influenza A viruses (IAV) are widely recognized respiratory pathogens in swine, causing fever,respiratorydistressandretardedweightgain.ThemorbidityandmortalityforIAVscanbeworsenedbymixedviralorbacterial infec\ons.EmerginginfluenzaDviruses(IDVs)werefirstiden\fiedinsickpigswithrespiratorydiseases.Ourrecentstudysuggestedthat,withinasamplepopula\onofIAVposi\veferalswine(n=96),42%hadan\bodiestobothIAVandIDV,sugges\ngthehost-pathogenecologyofinfluenzavirusespossiblyincludesfrequentco-infec\onswithIAVandIDV.Inthisstudyourgoalistodetermineifco-infec\onofIAVandIDVcreatessynergis\ceffectsinthehost.WeinfectedIAVandIDVseronega\vedomes\cswine(n=26)with 1)106TCID50ofIAV,2)106TCID50ofIDV,3)106TCID50ofIAVand106TCID50ofIDV,or4)sterilePBSandmonitoredclinicalsigns,completebloodcellcountsandviralsheddinginnasalswabsfor5dayspostinocula\on(dpi).Clinicalsignswereminimalandconsistedoflethargyintwopigs,oneeachfromtheIAVandIDVgroups,observedat24hourspostinocula\on(hpi)intheIAVgroupandat24,48and72hpiintheIDVgroup.Thepigswereeuthanizedat5dpiandall upper and lower respiratory tract \ssues harvested. Next, we will quan\fy and compare viralshedding and viral an\gens in respiratory tract \ssues from the pigs across groups, and thepathogenesisinthese\ssueswillbealsobescoredandcompared.Ourdataexpecttoprovideinsightas towhether co-infec\onof IDVand IAV increasespathogenesis in swine compared to infec\onofeitherIDVorIAValone.

ResearchGrant:MississippiStateUniversityCollegeofVeterinaryMedicineStudentSupport:MississippiStateUniversityCollegeofVeterinaryMedicine

� 32

Poster#24

Theeffectsofcannabidiolonneuroinflamma'oninexperimentalautoimmuneencephalomyeli's

JamesM.Nichols,EvangelKummari,JessicaSherman,andBarbaraL.F.KaplanDepartmentofBasicSciences,CollegeofVeterinaryMedicine,MississippiStateUniversity,Starkville,MS

Mul\plesclerosisisaneurodegenera\veautoimmunediseasecausedbyaberranttarge\ngofmyelinsheathsbytheimmunesystem.Tomodelthisprocessexperimentalautoimmuneencephalomyeli\s(EAE)isinducedbyimmunizingmicewithpep\desderivedfrommyelinproteins,suchasMOG35-55

pep\de,whichcausestheimmunesystemtotargetthemyelinsheathsofthecentralnervoussystem(CNS).Previousstudiesfromourlabhaveshownthatthephytocannabinoidcannabidiol(CBD)iscapableofreducingclinicaldiseaseandneuroinflamma\onintheEAEmodelifgivenorallyfor5daysa}ertheini\a\onofdisease.Inourpreviousworkthereduc\oninclinicaldiseaseatday18correlatedwithareduc\oninMOG35-55specificIFN-γproducingCD8Tcellsinthespleenonday10.Basedonthisobserva\on,wehypothesizedthatthereduc\oninclinicaldiseaseseenwithCBDfor5daysa}erini\a\onofdiseasewouldbeaccompaniedbyareduc\oninneuroinflamma\on,withspecificdecreasesintheCD8Tcellpopula\onwithintheCNS.Toexamineneuroinflamma\onmoreclosely,CD3,CD4,andCD8stainswereusedtodeterminetherela\venumberandtypesofTcellswithintheCNS.Inaddi\on,GFAPandDAPIwereusedtostainastrocytesandnucleirespec\vely,whichallowedustomeasuretheareaofthelesionswithintheparenchymaoftheCNS.Asexpected,therewasareduc\oninbothlesionsizeandnumberofTcellspresentwithintheCNSwithCBDtreatment;however,thereduc\onwasmodest,sugges\ngthatotherfactorsalsocontributetotheneuroprotec\vecapabili\esoforalCBDintheEAEmodel.

ResearchGrant:P20GM103646StudentFunding:MSU-CVM

� 33

Poster#25

Biochemicaleffectsoforalchlorpyrifosinlungsofneonatalandadultmice

BSzafran,ABorazjani,RCarr,MKRoss,andBLKaplan

CenterforEnvironmentalHealthSciences,DepartmentofBasicSciences,CollegeofVeterinaryMedicine,MississippiStateUniversity,MississippiState,MS

Chlorpyrifos(CPF)isanorganophosphate(OP)pes\cideknowntoexhibittoxicityviainhibi\onofacetylcholinesterase(AChE)inthenervoussystem.Wepreviouslyshowedthatendocannabinoid(eCB)metabolizingenzymeswereevenmoresensi\vetoinhibi\onbyOPpes\cidesthanAChEinneonatalrats,leadingtoincreasedlevelsofeCBsinbrain.BecauseeCBsareknowntohaveimmunosuppressiveeffects,weareinves\ga\ngalinkbetweeneCBmetabolismandimmunityinadultsandneonatesexposedtoCPF.Wehypothesizedthatneonatalmicewouldbemoresensi\vethanadultmicetotheeffectsofCPFoneCBmetabolism.Adultmice(≥8weeksold)andneonatalmice(post-natalday10)weretreatedwithCPF(2.5mg/kgoral)orvehicledailyfor7days.Tissueswereharvested4hra}erfinaltreatment.Anandamide(AEA)and2-arachidonoylglycerol(2-AG)hydrolysisac\vi\esinspleenandbrainwerenotdifferentbetweenvehicleandCPF,butlung2-AGhydroly\cac\vitywasdecreasedbyCPFinadults.Lungmicrosomesfrombothagegroupsdemonstratedmarkedinhibi\onofcarboxylesterase(Ces)ac\vity,oneoftheknowneCBmetabolizingenzymes.LungCesac\vityinneonateswasmoresensi\vetoCPFthanadults.Ac\vity-basedprotein-profiling(ABPP)andimmunobloqngoflungmicrosomesconfirmedthatCes1waspresentinbothagegroups,andtheac\vitywasinhibitedbyCPF.ABPP-massspectrometryofneonatalmouselungmicrosomesiden\fied31serinehydrolases,andCes1d(themurineorthologueofhumanCES1,abundantinhumanmacrophages)wasselec\velyinac\vatedbyCPF.Furtherstudiesinbothagegroupswillexploretheroleofinhibi\onofCes1dbyCPFinpulmonaryinflamma\on.

Funding:MississippiStateUniversityCollegeofVeterinaryMedicineStudentSupport:MSU-CVMandNIHGrantR15GM128206

� 34

Poster#26

Compara'veanalysisofTRIM9expressioninphagocytes

AmandaKortum,DebTokarz,AshleyFletcher,AshleyKirby,andJeffYoder

Department of Molecular Biomedical Sciences and Compara\ve Medicine Ins\tute, North CarolinaStateUniversityCollegeofVeterinaryMedicine,1060WilliamMooreDrive,Raleigh,NC

The persistence of an immune response can contribute to the development of disease states,increasingtheextentof\ssuedamageorperpetua\ngthediseasecondi\on.Chronicinflamma\oniso}en characterized by high numbers of macrophages and neutrophils that release ROS, cytotoxicfactors,andcytokines,furtheramplifyinginflamma\on.Phagocyteshavebeenshowntocontributetodisease inboth laboratory-inducedandnaturalmodelsofchronic inflamma\on inveterinaryspecies.Inflammatory bowel disease, ischemic injury and allergies are a few examples of inflammatorycondi\ons shared by dogs, horses, and humans. Studying the cellular mechanisms required forphagocytemigra\on to sites of inflamma\onwill elucidate how these cells could be therapeu\callytargetedduringpersistentinflamma\on.TheE3ubiqui\nligaseTRIM9ishighlyexpressedinthebrainandmediatesaxonmigra\onandsynap\cvesiclerelease.Our labfirstreportedTRIM9expression inzebrafish phagocytes and demonstrated that disrup\ng its func\on in vivo alters macrophage cellshape andmo\lity.We hypothesize that TRIM9 expression is regulated by immune s\mula\on andplaysanessen\alroleinregula\ngmammalianphagocytefunc\on.Forthiswork,wewillcharacterizeTRIM9 expression in dog, horse,mouse and human phagocytes. Furthermore,we aim to determineTRIM9’sroleinimmunefunc\ons,suchasmigra\onandphagocytosisandbegintodefinetheTRIM9protein interactome. This compara\ve analysis of themolecular mechanisms involved in phagocytemigra\on and func\on has great poten\al for producing targeted therapeu\cs for both human andveterinarypa\entsthatsufferfrompersistentdamaginginflammatorystates.

Researchgrant:NIHR21AI076829,T32GM008776,T35ODO1107Studentsupport:none

� 35

Poster#27

Biologicalsexinfluencesmastcellac'va'onpahernsandassociateddiseaseseverity

EmilyMackey,AdamJMoeser

Gastrointes\nalStressBiologyLaboratory,MichiganStateUniversity,EastLansing,MI(Mackey,Moeser),DepartmentofLargeAnimalClinicalSciencesCVM,MichiganStateUniversity,EastLansing,MI(Moeser),Compara\veBiomedicalSciencesProgram,NorthCarolinaStateUniversityCVM,Raleigh,NC(Mackey)

Highlyprevalentanddebilita\ngmastcell(MC)-associateddiseases,includingallergy,irritablebowelsyndrome,andautoimmunedisordersexhibitasexbiaswithfemalesatgreaterrisk.Themechanismsunderlyingthesesexdifferencesremainpoorlyunderstood.Ourpreviousstudiesu\lizingMC-dependentmodelsofIgE-mediatedanaphylaxisandpsychologicalstress,demonstratedthatfemalemiceexhibitedmoreseverepathophysiologyandincreasedMCmediatorreleasecomparedtomales.Theobjec\veofthisstudywastounderstandthemechanismsofsexualdimorphisminMCdisease.Ourhypothesisisthatheighteneddiseaseinfemalesisduetosex-specificdifferencesinMCac\va\onpaperns.Toinves\gate,weperformedtranscrip\onalanalysisonIgE-DNPallergen-ac\vatedmaleandfemalebonemarrow-derivedMCs(BMMCs).UsingIngenuityso}ware,wediscoveredasimilarpapernofIgE-DNPac\vatedpathwaysbetweenmaleandfemaleBMMCs.However,manyofthesepathwayswereupregulatedtoagreaterextentinfemaleBMMCsincludingsphingosine-1-phosphatesignaling,leukocyteextravasa\on,NF-κBsignaling,andchemokinesignaling.Ouranalysesalsorevealedup-anddownregula\onofsex-specificpathways.Forexample,maleBMMCsexhibitedupregulatedpathwaysoftranscrip\onalrepressionanddownregulatedpathwaysofcellcyclecontrolwhilefemaleBMMCsexclusivelyexhibitedupregula\onofhis\dinedegrada\onanddownregula\onofaminoacidbiosynthesis.Together,thesestudiesrevealnewinsightintosexdifferencesinMCbiologyanddiseasethatcorrelatewiththefemalesexbiasinhumans.Furtherelucida\ngtheroleofsexinMCac\va\onislikelytoprovidenoveltherapeu\capproachestoMCdiseases.

Funding:ThisstudywasfundedbyNa\onalIns\tutesofHealthgrantsNIHR01HD072968(toA.J.M.)andNIHF30OD025354(toE.M.).

� 36

Poster#28

Adapta'onof'lapia(Oreochromisnilo:cus)pituitaryculturetoanintermihentflowrespirometrysystemrevealsendocrineandenvironmentalregula'onofoxygenconsump'onrate

HannahReynolds,DavidBuchwalter,andRussellBorski

Compara\veBiomedicalSciences-CollegeofVeterinaryMedicine(Reynolds),DepartmentofBiologicalSciences(Buchwalter,Borski)-CollegeofSciences,NorthCarolinaStateUniversity,Raleigh,NorthCarolina Anorganism’sabilitytoregulateit’smetabolicrateinthefaceofphysiologicalandenvironmentalstressorsisessen\altosurvival.Thusly,theabilitytomeasureoxygenconsump\oninanorganism,organ,or\ssueisofpar\cularinteresttoresearchersfromawidevarietyoffields.Intermipentflowrespirometry(IFR)isapowerfulexperimentalproceduretypicallyusedtomeasureoxygenconsump\onrate(OCR)inaqua\corganisms.Inthistechnique,shortperiodsofclosed-chamberoxygenconsump\onmeasurementsareinterspersedwithregularflushing.ThismethodallowsfortheregularmeasurementofOCRsoverlongperiodsof\mewithouttotaldeple\onofoxygenorthebuild-upofwaste.Forthesereasons,IFRhasbecomeanimportantpartoftheaqua\cphysiologytoolbox.However,toourknowledge,noonehasusedIFRtomeasureoxygenconsump\onincultured\ssueororgans.Inthepresentstudy,thecultureoftherostralparsdistalis(RPD)ofthe\lapia(Oreochromisnilo+cus)pituitaryglandwasadaptedtoanintermipentflowrespirometrysystem.Tilapiaarephenomenalosmoregulators,abletoacutelywithstandwidefluctua\onsinenvironmentalsalinity.Thisphysiologicalresponsedependsontheac\onsoftheRPDhormoneprolac\n.Thus,themetabolicrateoftheRPDishigh,buttunable.Oncetheculturewasvalidated,theintermipentflowrespirometrysystemwasusedtoprobetheeffectsofosmolalityandthecatabolicstresshormonelep\nonpituitaryOCR.Hyper-andhypoosmo\cculturemediawereassociatedwithdecreasedandincreasedOCRs,respec\vely.Addi\onallycontrarytowhatisseeninmammals,ourresultssuggestlep\nactstodecreasetheOCRinthe\lapiapituitary.

ResearchGrant:NSFStudentSupport:GAANNFellowship

� 37

Poster#29

Knock-downofTMEM150Aresultsinincreasedcytokineproduc'on

JessicaL.RomanetandJeffreyA.Yoder*DepartmentofMolecularBiomedicalSciences,CenterforHumanHealthandtheEnvironment,andCompara\veMedicineIns\tute,NorthCarolinaStateUniversity,Raleigh,NCUnitedStates

Transmembrane Protein 150A (TMEM150A/TM6P1/DRAM5) is a member of the TMEM150/damage-regulatedautophagymodulator(DRAM)familyofproteinsthatpossesssix-transmembranedomainswithbothtermini posi\onedwithin the cytoplasm. Fivemembers of this family have been reported in human, and ofthose,threehavebeenimplicatedinregula\ngautophagy.Althoughautophagyismostwell-knownforcellularhomeosta\cdegrada\onoforganellesandcellsurvivalprocesses,autophagyhasalsobeenlinkedtoimmune-related func\ons. Forexample, theengagementofToll-like receptor4 (TLR4)by the lipopolysaccharide (LPS)component of gram nega\ve bacteria can induce autophagy. Based on the observa\ons that mul\pleTMEM150/DRAM familymembers have been implicated in autophagy and that, through its interac\onswithphospha\dylinositol 4-kinase type III alpha (PI4KIIIa), TMEM150A can regulate the produc\on of PI(4,5)P2 (acomponent in theTLR4pathway),weasked if there isa func\onalconnec\onbetweenTMEM150AandTLR4signaling. Knock-down of TMEM150A in cell culture led to significant increases in TLR4-induced cytokinesecre\onaswellasincreasesincytokinetranscriptlevels.Parallelexperimentsdemonstratedthatknock-downof TMEM150A triggered drama\c altera\ons in the ac\vity of mul\ple transcrip\on factors sugges\ng thatTMEM150Afunc\onstoregulateimmune-relatedgeneexpression. Insummary,weprovidethefirstevidencethat TMEM150A plays a role in regula\ng cytokine produc\on likely through a global role in regula\ngtranscrip\onfactorac\vity.

� 38

Poster#30

CharacterizingaNaturallyOccurringCanineModelofNeuropathicPain

Authors:SparksCR,GorneyA,WilliamsK,StachelAF,LascellesBDX,OlbyNJ

DepartmentofClinicalSciences(Sparks,Gorney,Stachel,Lascelles,Olby),Compara\veMedicineIns\tute(Lascelles,Olby),NorthCarolinaStateUniversityCollegeofVeterinaryMedicine,Raleigh,NC.

Chiari-likeMalforma\onandSyringomyelia(CMSM)isahighlyprevalentdiseasecomplexinCavalierKingCharlesSpaniels(CKCS)thataffectsthebrainandspinalcordandcausessevereneuropathicpainanditch.Thiscondi\oniswidespreadandnaturally-occurringinCKCSmakingitanidealtransla\onalmodelofChiari-type1malforma\on(CM1),asimilarcondi\oninhumans,andforstudyingneuropathicpain.Thebiggestchallengeinanystudyofpainisreliablequan\fica\on.Therefore,thepurposeofthisstudywastoobtainmeasureabledataonpaininacohortofCKCSandtocomparethesedatawiththepresenceandseverityofCMSMdeterminedbyMRI.Fi}y-twoclient-owneddogswererecruitedandownerswereaskedtocompletetwoques\onnaires.Dogsunderwentneurologicalexamina\onsandMRI.Specializedhemosta\cforcepswereusedformechanicalquan\ta\vesensorytes\ng(QST)ontheneck.Thirty-fourdogshadSMand36werepainfulonneurologicalexamina\on.Ownersreportedscratchingin35dogs,painin30,and28werereportedtohavebothpainandscratchingsigns.TherewasnosignificantdifferencebetweenthepresenceorseverityofSMandpainonneurologicalexamina\on,QSTdata,orowner-reporteddata(P>0.05).However,dogsthatwerepainfulonneurologicalexamina\onhadsignificantlylowerthresholdstomechanicaltes\ngwithameanthresholdof2.1kgs(SD:0.76kg)comparedtothosethatwerenotpainful(mean=2.7kgs,SD=0.54kg)(P=0.003).ThesefindingsshowthatmechanicalQSTmaybeausefultoolforbridgingthegapbetweenathomeandinhospitalobserva\onsaswellasforclinicaltrials.Also,therela\onshipbetweenCMSMandpaindeservesdeeperexamina\on.

ResearchGrant:TheAmericanCavalierKingCharlesSpanielClubCharitableTrustthroughtheAmericanKennelClubCanineHealthFounda\onStudentSupport:GeorgeHHitchingsNewInves\gatorAward;AVMA/AVMF2ndOpportunitySummerResearchAward

� 39

Poster#31

An'microbialresistancedynamicsinfoodborneCampylobactercoliisolatesusingMarkovrandomfieldnetworks

Chris\neA.Wang,WilliamJ.Love,SidThakur,Cris\naLanzas

DepartmentofPopula\onHealthandPathobiology,CollegeofVeterinaryMedicine,NorthCarolinaStateUniversity,Raleigh,NC

An\microbialresistancethreatenspublichealthbyreducingtheefficacyofan\microbialtreatmentsforinfec\on.Useofan\microbialdrugsmayselectforresistancetothosedrugsaswellasotherdrugsinunrelatedclasses.Consequently,collateralresistance,whichmayresultfromvariousmechanismsofgene\clinkageinbacterialgenomes,maydriveemergenceandpersistenceofmul\drug-resistance(MDR).Tradi\onalanaly\calmethodsfocusonresistancetoindividualdrugs,butarelesssuitableforevalua\ngMDRdynamicsbecausetheydonotquan\fyjointdistribu\onsofminimuminhibitoryconcentra\on(MIC)formul\pledrugs.ThisstudyevaluatedphenotypicMDRdynamicsusingMarkovrandomfieldnetworks(called“R-nets”).WehypothesizedthatcollateralresistanceinfluencesMDRevolu\on,asreflectedthroughcorrelatedphenotypicMICsofunrelateddrugsa}ercontrollingforconfoundingvariables.Totestthishypothesis,weusedR-netstoquan\fyjointMICdistribu\onstoninean\microbialdrugsamongCampylobactercoliisolatedfromagriculturalswineherdsexperiencingvaryingdegreesofan\microbialexposure.Wefoundhighlevelsofmacrolide-andtetracycline-resistanceinC.coliisolatesfrompigsthatwereandwerenotexposedtoan\microbials.UsingR-nets,wefoundthatMICsformacrolidesandtetracyclinewereassociatedwithoneanother,andwithMICforunrelateddrugslikeciprofloxacin.Theseresultsprovidephenotypicsupportfortheplausibilityofcollateralresistanceinthesepopula\onsofC.coli.Futurestudieswillusethesesameisolatestoiden\fygene\clinkagesofmacrolide-,tetracycline-,andciprofloxacin-resistance,giventheirimportancetoclinicalmedicine.

ResearchGrant:None

StudentSupport:NCSUProvost’sFellowship

� 40

Poster#32

CutaneousMalasseziaspp.dysbiosisincanineallergicderma''sbynext-genera'onsequencing(NGS)

CMeason-Smith,SDLawhon,TOlivry,ARHoffmann

DepartmentofVeterinaryPathobiology,CollegeofVeterinaryMedicineandBiomedicalSciences,TexasA&MUniversity,CollegeSta+on,TX77843(Meason-Smith,Lawhon,Hoffmann)DepartmentofClinicalSciences,CollegeofVeterinaryMedicineandCompara+veMedicineIns+tute,NorthCarolinaStateUniversity,1060WilliamMooreDrive,Raleigh,NC27607,USA(Olivry)

DNAsequencingtechnologieshaverevolu\onizedthestudyofskincommensals,howtheycontributetohealth,andtheirroleindisease.Thepurposeofthisstudyistoclassifyskin-associatedMalasseziatothespecieslevelwithphylogene\canalysisofNGSdata,andtoconfirmwithreal-\mequan\ta\vePCR(qPCR).DNApreviouslyextractedfromskinswabs(n=192)of10healthydogs,8non-lesionalallergicdogs,and8laboratorydogswithinducedatopiclesionswereincludedinthisstudy.MalasseziaNGSsequencesfromall192sampleswerespeciatedbyalignmenttoapublishedMalasseziaspp.databasewiththeopen-sourcebioinforma\csso}warePplacer.Quan\ta\vePCRtarge\ngM.pachyderma+s,M.restrictaandM.globosaconfirmedthatM.pachyderma+swassignificantlymoreabundantonswabstakenfromthelaboratorycolonyofdogscomparedtoclientownedhealthyandallergicdogs(P<0.05).Phylogene\canalysisof37,000NGSMalasseziasequencesfromhealthyandnon-lesionalallergicdogsshowedM.restrictawasmoreabundantonhealthyskin(P<0.05),whileM.pachyderma+swasmoreabundantonnon-lesionalallergicskin(P<0.05).Molecularmethodologiesareprovingtobeusefulinthestudyofskincommensals,andmayindicatethatM.restrictaandM.globosaactasprotec\vecommensalsonhealthyskin,whilethepathogenicM.pachyderma+sdominatestheskinofnon-lesionalallergicdogs.Comparisonsofquan\ta\veandrela\veabundancemethodsarenotalwaysconsistentandshouldbeconsideredinthechoiceofmethodsforfuturestudies.

Researchgrant:self-funded.Studentsupport:self-funded.

� 41

Poster#33

Contribu'ngeffectoforganochlorineexposureonAtlan'cbohlenosedolphindeathsfrommorbillivirus

JenniferCossaboon,BirgitPuschner,GinaYlitalo,DeborahFauquier,andTraceyGoldstein

OneHealthIns\tute(Cossaboon,Goldstein),MolecularBiosciences(Puschner),SchoolofVeterinaryMedicine,UniversityofCalifornia,Davis,CA;NorthwestFisheriesScienceCenter(Ylitalo),Na\onalMarineFisheries(NMFS),Seaple,WA;MarineMammalHealthandStrandingResponseProgram(Fauquier),NMFS,SilverSpring,MD

Dolphinmorbillivirus(DMV)isasubstan\althreattocetaceanpopula\onsduetoitsimmunesuppressioneffects,interspeciestransmission,andhighmortalityrate.Thoughadirectcausallinkhasnotbeenmade,chemicalpollu\onhasbeenimplicatedinpoten\allyincreasingsuscep\bilitytoDMVinfec\oninnearshorecetaceans.ArecentoutbreakalongtheUSEastCoastresultedinthedeathofover1600Atlan\ccommonboplenosedolphins.Wehypothesizethatdolphinsthatdiedfrommorbillivirusinfec\onhadsignificantlyhighermeanΣPCBandmeanΣDDTconcentra\onsinblubberandbrain\ssuecomparedtoboplenosedolphinsthatinhabitedthesameareasandstrandedbeforetheDMVoutbreak.Pairedbrainandblubbersamplesfrom15confirmedDMVcasesandtencontroldolphinsarebeinganalyzedbyGC/MSfor51PCBcongenersandsixDDT-relatedcompounds.Contaminantlevelsinbrain\ssuehadnotbeenmeasuredpreviouslyinDMVcasesdespitethebrainbeingoneoftheprimaryloca\onsforpathologicallesions.Preliminaryresultsfromthisstudyindicatethattherearesubstan\allyhigherPCBconcentra\onsinthebrainsofDMVcasesthanpreviouslyreportedindolphinsthatdidnotdiefromthevirus.Lipidcontentandlipidclassesarealsobeingdeterminedandwillrevealhowindividualcongenerspar\\onbetweenblubberandbrain\ssueindolphinsthatdiedfromDMVversusthecontroldolphinsthatdiedfromothercauses.Addi\onally,aneworganiccontaminantextrac\onprocedureisbeingevaluatedonasubsetofthesamplesusingPhreephospholipidremovalplatesthatmayprovideamoreefficient,high-throughputmethodologyforfuturebiomonitoringofcontaminantsinmarinemammal\ssues.

ResearchGrant:Na\onalMarineFisheriesService

StudentSupport:“StudentsTraininginAdvancedResearch”Fellowship(SchoolofVeterinaryMedicineendowmentfunds,GoldsteinLabfunding)

� 42

Poster#34

Evalua'onofanovelsolubleepoxidehydrolaseinhibitorintheUCDavisType2DiabetesMellitusRatModel

ChaseGarcia,JamesGraham,PeterHavel,BruceHammock

DepartmentofMolecularBiosciences,SchoolofVeterinaryMedicine(Graham,Havel),DepartmentofComprehensiveCancerCenter(Hammock),UCDavis,Davis,CA

Type2DiabetesMellitus(T2DM)isaseriousandincreasinglyprevalentmetabolicdiseasethatischaracterizedbyincreasedbloodglucoselevels,insulininsensi\vity,andß-cell/isletdysfunc\on.OneofthecentralcomponentsofthepathophysiologyofT2DMinhumansisageneralinflammatorystatewhichcanbeprophylac\callyortherapeu\callytargeted.Onepoten\alwayoftarge\ngthisdysregula\onisviasolubleepoxidehydrolaseinhibitors(sEHI)whichhavebeenshowntohavean\-inflammatoryeffects.AsapartofDr.PeterHavel’slaboratoryandincollabora\onwithDr.BruceHammock’slaboratoryweinves\gatedthetherapeu\cproper\esofanovelsEHIintheUCDavisType2DiabetesMellitusratmodel.DuringthispilotstudyweareperformedadualtreatmentoffishoilandthesEHIontheUCDavisT2DMRatModel,targe\ngtheinflammatorye\ology.Thetreatmentandcontrolgroupsweren=6.ThegoalofthestudyistoseeifsEHIshaveaprotec\veeffectanddelayT2DMdevelopmentintheUCDavisT2DMratmodel.Fromourpreliminaryresultswesawsomeposi\veeffectsfromthefishoilandsEHIonthetreatmentgroupasshownby:delayeddiabetesonset;lowerbloodglucose,triglyeride,andtotalcholesterollevels;andimprovedoralglucosetolerancetestresults.ThesepreliminaryresultssuggestsEHIsmayhaveaposi\veeffectbydelayingonsetofT2DMandthatfurtherinves\ga\oniswarranted.

ResearchGrant:Dr.Havel’sDiscre\onaryFundingStudentSupport:StudentsTraininginAdvancedResearch(STAR)Program

� 43

Poster#35

L.plantarumrepairsintes'nalepithelialbarrierdamageinchronicSIVinfec'onthroughPPARamediated-mitochondrialrescue

KaqHorng1,ClarissaSantos-Rocha1,GuochunJiang1,AnneFenton1,LaurenHirao1,IrinaGrishina1,SandipanDapa2,GinoCortopassi2,MariaMarco3,SumathiSankaran-Walters1,SatyaDandekar1

1DepartmentofMedicalMicrobiology&Immunology,UniversityofCalifornia,Davis,SchoolofMedicine;2DepartmentofMolecularBiosciences,UniversityofCaliforniaDavis,SchoolofVeterinaryMedicine;3DepartmentofFoodScience&Technology,UniversityofCalifornia,Davis,Davis,CA,USA. HIVinfec\oncausespersistentinflamma\onand‘leakygut’asaresultofimmunedysfunc\onandepithelialbarrierdisrup\on.Despiteeffec\vean\-retroviraltherapy(ART),completeimmunerecoveryandgutbarrierintegrityarenotachieved.Novelapproachestorestorethegutmicroenvironmentareimpera\vetoposi\ontheimmunesystemforviraleradica\on.Toiden\fymechanismsforinterven\on,weperformedintes\nalloopsurgeriesusingthenonhumanprimatemodelofAIDStocaptureresidentintes\nalmicrobiota,\ssuemicroenvironments,andtheirinterac\ons.Probio\cL.plantarumwasinjectedintoilealloopstoiden\fyhostandbacterialcontribu\onstomucosalresponsesinSIVinfec\on.Wefoundthatdisrup\onofepithelial\ghtjunc\onsinchronicSIVinfec\onwasrepaireda}er5-hourexposuretoL.plantarumindependentofCD4+Tcellrecovery.Metabolomicandgeneexpressionanalysesrevealedthatmitochondrialdysfunc\onandimpairedbeta-oxida\onwereassociatedwithSIVinfec\onandreverseda}erexposuretoL.plantarum.Ac\va\onofPPARasignalingbyL.plantarumrestoredmitochondrialac\vityinchronicSIVinfec\on.OurfindingsinCaco-2cellculturessuggestthatepithelialbarrierfunc\onisregulatedbyATP-linkedrespira\on,whichisapenuatedduringSIV/HIVinfec\onandcanbeaugmentedbyPPARamodula\on.Integra\onofHIV-inducedmitochondrialdysfunc\onwithmicrobiota-mediatedchangesinthegutprovidesnewstrategiesforHIVdiseasemanagementandop\miza\onof\ssuerecoveryduringART.

ResearchGrant:NIHR01AI123105

StudentSupport:NIHF30GM131457,UCDSVM

� 44

Poster#36

DecodingERKRegula'onoftheCellCycletoDirectRa'onalCombinatorialTherapy

DevanMurphy1,JohnG.Albeck1

DepartmentofMolecularandCellularBiology,CollegeofBiologicalSciences,UniversityofCalifornia,Davis,Davis,CA1

Onehallmarkofcancerisuncontrolledcellprolifera\on,andcancercellso}encarrymuta\onsintheRas/MAPKpathwaythatregulatecellcycleevents.ERK,theterminalkinaseoftheMAPKpathway,increasestheexpressionofcyclins,whichcontrolthecellcycleincomplexwithcyclin-dependentkinases(CDKs).Paradoxically,whileERKisnecessaryforcellprolifera\on,excessiveac\vitycaninducecellsenescence.ERKisanimportantpharmacologictargetforan\cancertherapies;however,durableandpotentERKsuppressionisclinicallydifficulttoachieve.Thisstudyinves\gatesthecombina\onofERKandCDKinhibi\onforsynergis\csuppressionofprolifera\on.Usinglive-cellmicroscopyandimprovedfluorescentreporters,ERKac\vitywasquan\fiedthroughoutthecellcycleatatemporalresolu\onthatwaspreviouslyinaccessible.Regula\onofcyclin-dependentkinaseinhibitorproteins(CKIs)willbeexaminedtodeterminethemechanis\cbasisforchangesinprolifera\vethreshold.Together,thisworkwillprovidethedataneededtoop\mizecombinedCDKandERKinhibi\onforreducedtumorgrowth.

Funding:Boehringer-IngelheimAnimalHealth(BI);NIHR01

� 45

Poster#37

ELISACompe''onAssaysforAn'bodiesCapableofBlockingPD-L1Ig

HarmanpreetPanesar,JinWookChoi,StephenJMcSorley

CenterforCompara\veMedicine,SchoolofVeterinaryMedicine,UniversityofCalifornia,Davis

PD-1isaninhibitoryreceptorthatbindstoPD-L1onthesurfaceoftumorandan\genpresen\ngcellsinthetumormicroenvironment,causingsuppressionofT-cellac\vityandtumorprogression.Humanclinicaltrialswithan\PD-1monoclonalan\bodies,nivolumabandpembrolizumab,showedanobjec\veresponserate(ORR)of30%to40%withmelanomaand87%withrelapsedorrefractoryHodgkin’slymphoma.WehavepreviouslyexploredthedevelopmentofcaninePD-1/PD-L1reagentsforpoten\alveterinaryapplica\ons.5an\bodiescapableofblockingPD-1IgandPD-L1Igwerepreviouslydeveloped.Inthisstudy,wearefurtherinves\ga\ngthenatureofepitopebindingbyfouran\bodiesbyperformingELISAcompe\\onassays.Thesecaninereagentshavemul\plediagnos\candtherapeu\capplica\onsinthecontextofcanineoncology.

� 46

Poster#38

SYCP3ImpairsBRCA2IncreasingRiskofCancer

AshSundaram1,HangPhuongLe1,JieLiu1,SumitSandhu1,AlexanderBorowsky3,NeilHunter1,WolfDietrichHeyer1

1DepartmentofMicrobiologyandMolecularGene\cs,UniversityofCalifornia,Davis,CA95616,USA.2DepartmentofPathologyandLaboratoryMedicine,SchoolofMedicine,UniversityofCalifornia,Davis,CA95616,USA.

BRCA2 maintains genomic integrity by func\oning in homologous recombina\on (HR) and therebysuppressestumorforma\on.BRCA2recruitsotherproteinssuchasRAD51insoma\ccellsandRAD51andDMC1 ingermlinecells to func\on inkeystepsofHR.LossofBRCA2func\on isassociatedwithincreased risk of breast and other cancers. Mechanisms that inac\vate BRCA2 func\on other thandirectmuta\onalinac\va\onareyettobedetermined.MyresearchaddressesthisgapinknowledgeanddefinesanewmechanismbywhichmisexpressionofthegermlineproteinSYCP3insoma\ccellsinhibitsBRCA2-mediatedHR.SYCP3 is an essen\al structural component of themeiosis-specific synaptonemal complex. SYCP3 istypically expressed only in germline cells but not in soma\c cells. Emerging evidence indicates thatSYCP3ismisexpressedincertaincancers.ThestructuralroleofSYCP3inmeiosisiswellunderstoodbutnotmuchisknownaboutitspoten\aleffectsinsoma\ccells.Recently,itwasreportedthatinsoma\ccellsSYCP3interactswithBRCA2andimpairsrecruitmentofRAD51involvingmechanismsthatremaintobedefined.Thegoalofmyresearchistoestablishthemechanism,bywhichSCYP3regulatesBRCA2func\oninHR.MyhypothesisisthatSYCP3regulatesthedifferen\alinterac\onofBRCA2withRAD51andDMC1.SpecificAim1willestablishthebiochemicalmechanismbywhichSYCP3regulatesBRCA2func\onbyinvitro assays using purified proteins. Specific Aim 2 will use cell-based models to determine thebiologicalsignificanceoftheinterac\onbetweenSYCP3andBRCA2onHRefficiency.ThefindingsfromthisproposalwillestablishSYCP3expressionintumorsasapoten\albiomarkerforHRdeficiency.

ResearchGrant:NoneStudentSupport:MCBNIHT32(T32GM007377)

� 47

Poster#39

ViralRNA'tersinkidneyscollectedfrombirdsexperimentallyinfectedwithinfec'ousbronchi'svirus

JenniferC.G.Bloodgood,AlindaJ.Berends,AndreaLaconi,JavierDenizMarrero,ErikA.Weerts,SjaakJ.deWit,M.HélèneVerheije

SoutheasternCoopera\veWildlifeDiseaseStudy,CollegeofVeterinaryMedicine,UniversityofGeorgia,Athens,GA(Bloodgood),DepartmentPathobiology,FacultyofVeterinaryMedicine,UtrechtUniversity,Utrecht,NL(Berends,Laconi,DenizMarrero,Weerts,Verheije),GDAnimalHealth,Deventer,NL(deWit)

Infec\ousbronchi\svirus(IBV),ahighlycontagiousviraldiseaseofchickenswithglobaldistribu\on,isofprimaryconcerninthepoultryindustryduetoeconomiclossesincurredfromaffectedbirds.Thevirusini\allyinfectstheupperrespiratorytract,resul\ngindecilia\onofthemucociliaryapparatus.IBVcanalsoreplicateanddestroyotherepithelialsurfaces.Inlayers,lesionsintheoviductleadtodeclinesineggproduc\onandquality,whileinbroilerseconomiclossesareprimarilyduetopoorweightgainandfeedefficiency.Inaddi\on,theIBV-QXstrainisnephropathogenic,causingseverenephri\sandhighmortality.CurrentunderstandingofIBV-QXpathogenicityislimited.Thus,theobjec\vesofthisstudyweretodetermineiftherearedifferencesinkidneyIBVviral\tersin1)layerversusbroilerchickens,and2)chickensinoculatedwithwild-typeIBV-QXcomparedtothederiva\veQXvaccine.Intotal,58specificpathogenfree(SPF)layersand58SPFbroilerswereincludedinthisstudy.Ofthese,24ofeachwereinoculatedintranasallywiththevaccinestrain,24ofeachwiththewild-typestrain,and8ofeachweremock-inoculatedasacontrol.Chickenswereeuthanizedseriallyfromday1through8post-inocula\on,andkidneyviral\tersweredeterminedusingRT-qPCR.Nosignificantdifferenceswerefoundbetweenlayersandbroilers,howeverchickensinoculatedwiththewild-typevirushadsignificantlyhigher\tersthanthoseinoculatedwiththevaccinestrain.Thisinforma\onwillbecombinedwithhistologicalandimmunohistochemistrydatafromthesamestudytoelucidatewhetherthepresenceoflesionsandviralproteinexpressioncorrespondswithviralRNApresence.

ResearchGrant:NoneStudentSupport:BoehringerIngelheimVeterinaryScholarsProgram

� 48

Poster#40

MumpVirusNucleoproteinDomain“Top”AffectsDefec'veInterferingPar'cleProduc'on.

JacqulineRisalvato,JamesZengel,LeiLi,HenryWan,MingLuo,BiaoHe

Infec\ousDiseases(Risalvato,Zengel,He),CollegeofVeterinaryMedicine,UniversityofGeorgia,Athens,GA;BasicSciences(Li,Wan),CollegeofVeterinaryMedicine,MississippiStateUniversity,Starkville,MS;Chemistry(Luo),GeorgiaStateUniversity,Atlanta,GA

Mumpsvirus(MuV)isanega\ve-sensesingle-strandedRNAvirusbelongingtothefamilyParamyxoviridae.Ahumanpathogen,MuVisresponsibleforacuteinfec\onoftheparo\dglands,andcancauseseverecasesofencephali\s,meningi\s,anddeafness.ThenonsegmentedRNAgenomeofMuVisencapsidatedbythenucleocapsidprotein(NP),whichformstheribonucleoprotein(RNP)complex–whichservesasatemplateforRNAsynthesis.TomakeRNAaccessibletotheviralpolymerase,aconforma\onalchangewithinNPmustoccur.CrystalstructureanalysisoftheNPofparainfluenzavirus5(PIV5),aparamyxoviruscloselyrelatedtoMuV,indicatesthatanα-helixclosetotheRNAgenomebecomesflexiblewhenRNAisremoved.ThisregionoftheNPislikelyresponsiblefortheconforma\onchangewhichallowsthepolymerasetoaccessRNAfortranscrip\onandreplica\on.Toexaminethefunc\onalityofMuV’sNP,pointmuta\onsweremadeinMuVNPproteincorrespondingtoPIV5atsitesG185P,A197Q,Q200R,andgroupsdenotedasTop(N63G,P139D,A197Q),Tip(P109E,N121G,A124R),andBopom(G21S,S29T,P43N,R93Q,R304Q).The“Top”MuVmutantexhibitednormalgrowthkine\csatlowmul\plicityofinfec\ons(MOIs);however,athighMOI’stheviruscouldnotefficientlyreplicate.Furtheranalysisindicatesthatproduc\onofdefec\veinterfering(DI)par\cleswasenhancedinthemutantvirus.Understandingtheproduc\onofDIpar\cles,whichcanleadtoincreasedinterferonproduc\on,willinvariablyleadtoabeperunderstandingofMuVpathogenesisaswellasitsreplica\on/transcrip\onprocess.

ResearchGrant:Na\onalIns\tuteofHealthGrantRO1AI106307

StudentSupport:None

� 49

Poster#41

Cytokineexpressionfollowingporcineisletxenogragsinimmunosuppressedandtolerantnonhumanprimates

ScopH.OpplerJr.1,LucasA.Mutch2,JodyL.Janecek2,SabarinathanRamachandran3,MelanieL.Graham2,4

1CollegeofVeterinaryMedicine,UniversityofMinnesota,St.Paul,MN;2PreclinicalResearchCenter,DepartmentofSurgery,UniversityofMinnesota,St.Paul,MN;3SchulzeDiabetesIns\tute,UniversityofMinnesota,Minneapolis,MN,4VeterinaryPopula\onMedicine,UniversityofMinnesota,St.Paul,MN

Pancrea\cisletcelltransplanta\onhasdemonstratedvalueasatherapeu\cmodalityinType1diabetesthatcanrestoreinsulinindependenceandlowerriskofsecondarycomplica\ons.Althoughhighlyeffec\ve,scarcehumandonorpancreatahaslimiteditswidespreaduse.Onepoten\alsolu\onistheuseofporcineislets,whichproduceanear-iden\calinsulin.Porcineisletxenogra}sundergorejec\onviaaprimarilyT-cell-mediatedprocessinnonhumanprimate(NHP)models.Xenogra}survivaldependsonmi\ga\ngthisresponse,viaeitherlong-termimmunosuppression,orideally,inducingastateofimmunetolerancetothegra}.Cytokineshelpregulatethebalancebetweenpromo\onandimpairmentofgra}survival,someenforcingtolerancebyinhibi\ngimmunecells,andothersbreachingtolerancebycausingcytotoxicdamage.CharacterizingcytokineprofilesinxenotransplantedNHPsexposedtoeitherconven\onalT-celldirectedimmunosuppressionortolerogenicprotocolshasthepoten\altouncoverthemolecularbasisofregulatorymechanismsthatfostertoleranceandprolonggra}survival.Westudiedthesystemiccytokineresponsetoisletxenotransplanta\onin17diabe\ccynomolgusmacaquesthatreceivedeitherimmunosuppressionoratolerogenicprotocol.Cytokinesweremeasuredwithamul\plexassayfromserumsamplescollectedatserial\mepoints.Weanalyzedcytokineexpressionover\me,andcomparedthesepapernsacrossNHPsstra\fiedbygra}func\onaloutcomes.Inthefuture,weplantostudyhowcytokineexpressionvariesbycompartment,toevaluateaccuracyofcytokineprofilesinpredic\ngthefateoftransplantedislets,andtoexploittolerogenicmechanismswithtargetedcelltherapies.

ResearchGrant:Na\onalIns\tutesofHealthGrantU01AI120130StudentSupport:BoehringerIngelheimVeterinaryScholarsgrant

� 50

Poster#42

RNA-Seqiden'fiesmutuallyexclusivedriverinser'onsinPI3K-hyperac'vemammarycarcinomas

Authors:EmilyA.Pope1,2,MarkSokolowski2,MoritoKurata2,JingminShu2,AaronL.Sarver2,NuriA.Temiz2,WendyA.Hudson2,NicholasJ.Slipek2,WenlinYuan3,SomasekarSeshagiri3,DavidA.Largaespada2,4

Affilia'ons:1–UniversityofMinnesota,CollegeofVeterinaryMedicine,StPaulMN2–MasonicCancerCenter,UniversityofMinnesota,MinneapolisMN3-DepartmentofMolecularBiology,GenentechInc.4–DepartmentofPediatrics,UniversityofMinnesota,MinneapolisMN

Abstract:Themostcommoncarcinomasinwomen,andoneoftheleadingcausesofcancer-relateddeath,areinvasivemammarytumors.Crea\nginvivomodelsthataccuratelyrecapitulatemammarytumorigenesisisdifficultduetohighgene\cheterogeneitywithinandbetweentumors.Ac\va\ngmuta\onsinthecataly\csubunitofPI3Kareoneofthemostcommongene\caltera\onsinhumanbreastcarcinomas.Weconductedaforwardgene\cscreenusingaCre-inducibleSleepingBeauty(SB)transposonsysteminthecontextofPI3Khyperac\va\ontodiscovergene\ceventsthatcooperatewithanoncogenicPI3Kmuta\on.TheT2/Onc3transposonac\vatesendogenousproto-oncogenesorinac\vatestumorsuppressorgenesbyinser\onalmutagenesis.Inconjunc\onwithaR26-LSL-SB11transposaseand\ssue-specificCre,thetransposonmobilizesandintegratesintothegenome.MicewiththePI3Kmuta\onandSBhadacceleratedtumorigenesiscomparedtocontrols.RNAsequencingshowedmolecularsubtypeswithcorrela\ngT2/Onc3-inducedinser\onmuta\ons,includingestrogenreceptor(ER)posi\veandnega\vesubtypes.RNAandDNAsequencingdefinedcommoninser\onsitesoftheSBtransposon,allowingfordetec\onoffrequentlymutatedgenes.Weanalyzed244tumorsandiden\fied20tumorsuppressorgenesand35oncogenesascommoninser\onsites.Notably,somecommonRNAinser\onsites(R-CIS)weremutuallyexclusive,specificallyinser\onsinJup,Hras,Pten,andNotch1.Addi\onally,Pteninser\onswereassociatedwithER+tumors.Thismodelprovidesasourceofgene\callyheterogenousmammarytumorswiththesameini\a\ngmuta\on(PI3K)usefulforiden\fyingcoopera\ngpathwaysanddriversofspecifictumorphenotypes.

ResearchGrants:AmericanCancerSocietyResearchProfessorAward(toD.A.L.),Genentech/RocheInc.StudentSupport:BoehringerIngelheimVeterinaryScholarsGrant

� 51

Poster#43

SOS1ExpressioninCanineLeukemia

GabrielleRobbins,MichaelFarrar,JaimeModiano

CenterforImmunology(Robbins,Farrar),MasonicCancerCenter(Robbins,Farrar,Modiano),DepartmentofLaboratoryMedicineandPathology(Robbins,Farrar),CollegeofVeterinaryMedicine(Robbins,Modiano),UniversityofMinnesota,Minneapolis,MN

Oncogenesaregenesthathavethepoten\altocausecancerandareo}enmutatedorhighlyexpressedintumorcells.Themajorityofthe‘moreeasily’discoveredoncogeneshavebeeniden\fiedandsuchinforma\onhasfrequentlybeenusedtodevelopeffec\vetherapies.However,approachesusedtoiden\fyoncogenestypicallyfailtodetectcopynumberneutralgenomicrearrangements,suchasmicroinversions.Theselatergenomicrearrangementsmayrepresentagroupofmuta\onsthatplayasubstan\al,albeitunappreciated,roleincancer.

Bcellacutelymphoblas\cleukemia(B-ALL)isthemostcommonformofchildhoodcancer.Andmalignantlymphoprolifera\vediseasesalsoaccountforapproximately40%ofcanineneoplasia.Sos1isfrequentlymutatedinB-ALLanditsexpressioncorrespondswithdecreasedsurvivalinprevioushumanandmousestudies.WeexploredwhetheranovelintrachromosomalmicroinversionincaninescreatesasimilartruncatedformofSOS1inleukemias.Inhibi\onofSOS1proteincouldresultinpa\entremissionandelimina\onofaffectedBcells.Thisstudywillinves\gateanovelchangeinSOS1thatmaybepresentinleukemiaandothertypesofcancerandthusbeapoten\altherapeu\ctargetusing5’-/3’-RACEandqPCR.ResultsshowedonlyaminimalincreaseintheexpressionofthetruncatedSos1incanineleukemiasamplesbutadrama\cincreaseinexpressionincanineosteosarcomasamples.

ResearchGrant:UnknownStudentSupport:UniversityofMinnesotaSummerScholarsProgram

� 52

Poster#44

GenderDependentAltera'onsintheMechanicalResponseofCollagenVHaploinsufficientMurineTendons

JaclynA.Carlson,SnehalS.Shetye,AshleyB.Rodriguez,JessicaM.Johnston,MeiSun,SheilaM.Adams,DavidE.Birk,LouisJ.Soslowsky

McKayOrthopaedicResearchLaboratory(Carlson,Shetye,Rodriguez,Johnston,Soslowsky),UniversityofPennsylvania,Philadelphia,PA;MorsaniCollegeofMedicine(Sun,Adams,Birk),UniversityofSouthFlorida,Tampa,FL

Gender-specificdifferencesinbodystructureandcomposi\onmayexacerbatethedetrimentalchangespresentinpathologicaltendonsinClassicEhlers-Danlossyndrome(EDS)pa\ents.WehypothesizedthatfemaleclassicEDSmicewillhaveinferiortendonmechanicalproper\escomparedtomaleclassicEDSmice,buttherewillonlybedifferencesinstructuralproper\esduetogenderinwildtypetendons. AdultmaleandfemaleuninjuredWTC57/BL6andHETEDSmousepatellartendonswereused.ComparedtoWTfemales,WTmaletendonshadsignificantlyhigherfailureload,failurestress,\ssuemodulusand\ssues\ffness.Addi\onally,WTmalesexhibitedsignificantlyelevateddynamicmodulusat10Hzandacrossallstrains(2%,3%,4%).HETmaletendonshadasignificantlyhigherfailureloadthanHETfemales,withnodifferenceobservedin\ssues\ffness.HETmaleandfemalemiceshowedtrendingdifferencesat2%strain,0.1and1Hz,andat4%strain,1Hz.MaleHETtendonstrendedtowardsadecreaseins\ffnesscomparedtoWTtendons,withnootherdifferencebetweengenotypes. WTmalepatellartendonsdemonstratesuperiormaterialandstructuralproper\escomparedtoWTfemaletendons.Conversely,thesamedifferencesinstructuralproper\esseeninWTtendonswerenotpresentinHETmice.Thiscontras\ngfindingindicatesthatthestructuralproper\esofHETmaletendonswereaffectedbythereduc\onoftypeVcollagentoagreaterdegreethanthestructuralproper\esofHETfemaletendons,a}erconsideringtheinherentgender-differences.Thisstudydemonstratesthatsexplaysatendon-specificroleintendonhealth,andcaninfluencethedegreetowhichtendonproper\esofclassicEDSmiceareaffected.

ResearchGrants:ThisstudywassupportedbyAR065995,AR044745andthePennCenterforMusculoskeletalDisorders(P30AR069619).StudentSupport:None.

� 53

Poster#45

Thegenome-wideDNA-bindingproper'esoftheALS-associatedproteinTDP-43

PierceNathanson,XiangYu,JordanT.Mak,ShawnW.Foley,TravisL.Unger,BrianD.GregoryandAliceS.Chen-Plotkin

Cell andMolecularBiologyGraduateGroup (Nathanson, Foley),DepartmentofNeurology, PerelmanSchoolofMedicine(Nathanson,Mak,Unger,Chen-Plotkin),DepartmentofBiology,SchoolofArtsandSciences(Yu,Foley,Gregory),UniversityofPennsylvania,Philadelphia,PATAR DNA-binding protein 43 (TDP-43) is the major protein component of neuronal inclusionscharacterizing the fatal neurodegenera\ve diseases amyotrophic lateral sclerosis (ALS) andfrontotemporal lobar degenera\on with ubiqui\nated inclusions (FTLD-TDP). Disease-causingmuta\onsinthegenethatencodesTDP-43,TARDBP,furtherimplicateTDP-43indiseasepathogenesis.Originally iden\fied as a protein capable of binding HIV trans-ac\va\on response element DNA,researchhasemphasizedTDP-43’s roleasanRNA-bindingprotein, therebyneglec\nga fundamentalpropertyofTDP-43biology.Toaddressthis,weperformedchroma\nimmunoprecipita\onfollowedbyhigh-throughput sequencing (ChIP-Seq) inhumancells,demonstra\ng thatTDP-43 isagenome-wideDNAbindingprotein.Notably,TDP-43waspar\cularlyenrichedatsmallnuclearRNAgenesandALS-causa\vemuta\ons inTARDBP impairedTDP-43’sability tobindthese loci.Thesefindingspoint toapoten\al role for TDP-43 in snRNA biogenesis thatmay contribute to the disrupted splicing profilescharacteris\cofALSandFTLD-TDP.

ResearchGrants:Na\onal Ins\tutesofHealth (NIAK08AG033101 toACP), theBurroughsWellcomeFundCareerAwardforMedicalScien\sts(toACP)andtheBenaroyaFund(toACP)StudentSupport:Mentor(ACP),UniversityofPennsylvaniaBiomedicalGraduateStudies

� 54

Poster#46

Implica'onsoffree-rangingdogmovementpahernsforurbanrabiescontrol

BrinkleyRaynor,AndrewJohnson,MicaelaDelaPuente,RicardoCas\llo-Neyra

SchoolofVet.Med.(Raynor),Dept.ofBio.,Biomed.Grad.Studies(Johnson),Dept.ofBiostat.,Epid.&Informa\cs,PerelmanSchoolofMed.(Cas\llo-Neyra),Univ.ofPennsylvania,Philadelphia,PA;Zoono\cDiseaseResearchLab,SchoolofPublicHealthandAdministra\on,Univ.PeruanaCayetanoHeredia,Peru(DelaPuente).

In2015,acaseofcaninerabiesinArequipa,Peruindicatedthere-emergenceofrabiesinthecity.Despitevaccina\oncampaignsandringeuthanasiaoffree-rangingdogsaroundposi\vecases,theoutbreakhasspreadthroughoutthecityresul\nginnewcaseseveryweek.TheaimofthisstudywastoexplorehowtheurbanlandscapeofArequipaaffectsthespreadofcaninerabiesandcorrespondingcontrolmeasuresbyexaminingmovementpapernsoffree-rangingdogs.Todothis,wetracked23free-rangingdogsusingGlobalPosi\oningSystem(GPS)collars.Weanalyzedthespa\o-temporalGPSdatausingthe\me-localconvexhullmethod;aroundeveryrecordedloca\on,weconstructedconvexpolygons(hulls)usingaselectedsetofnearestneighborloca\ons.Weusedthesehullstoapproximatespaceusagebythedogs,includinghomerangeandu\liza\onarea,aswellas,direc\onalityofmovements,dura\onofstayindifferentareas,andrevisita\ontodifferentareas.Wefoundthattherewasgreatvaria\oninmovementpapernsbetweenindividualdogs.Themovementpapernswereaffectedbylocalenvironments.Specifically,waterchannels,anurbanfeatureofArequipathataredrymostoftheyear,werefoundtobeareasofhighmovement.Dogsthatu\lizedthewaterchannelshaddis\nctmovementpaperns.Thesefindingssuggestthatsomedogsusingthewaterchannelsas‘highways’havethepoten\altospreaddiseasefarbeyondtheringeuthanasiacontrolprac\ces.Astheseprac\ceshaveledtolocalresentment,controleffortsshouldfocusonarobustvaccina\oncampaignnotlimitedtoareaswheretherehavebeenrecentcases.

ResearchGrant:DepartmentalFunds-DepartmentofBiosta\s\cs,Epidemiology&Informa\cs,PerelmanSchoolofMedicine,UniversityofPennsylvania.StudentSupport:MedicalScien\stTrainingProgramGrant

� 55

Poster#47

TheSOSresponseisaCri'caltoBacterialColoniza'onoftheMammalianGut

AmandaSamuels,MarkGoulian,andRahulKohli DepartmentofMicrobiology,Virology,andParasitology,SchoolofVeterinaryMedicineandSchoolofMedicine(Samuels),DepartmentofBiology(Goulian),DepartmentofInfec\ousDiseaseattheSchoolofMedicine(Kohli),UniversityofPennsylvania,Philadelphia,Pennsylvania

Background: The ability of bacteria to rapidly adapt to environmental challenges has profoundimplica\ons for bacterial infec\ons. Bacterial stress response pathways enable bacteria to suriveenvironmentalchallenges.TheSOSresponseisastressresponsepathwaythatac\vatesinresponsetoDNA damage and promotes DNA repair. The SOS response is vital for bacterial survival through itsrepairofDNA,butsignificantly,culture-basedexperimentsdescribetheSOSresponseasbeingamajorcontributer to adap\ve mutagenesis and horizontal gene transfer, both of which increase genomicplas\city ul\mately enhancing survival, virulence, and adapta\on. In addi\on to modifying thegenome,invitro,theSOSresponsecontrolssomevirulencefactors,whichmaybecri\calforbacterialcoloniza\on and pathogenesis. Despite a large body of research describing the importantconsequences of the SOS response, liple work has been done to interrogate the par\cular hostenvironmentsthatinduceandrequiretheSOSresponseforsurvival.Results:Using amouse commensalE. coli strain, I demonstrate that the SOS response is cri\cal forcoloniza\onofthemurinegutbothinthepresenceandabsenceofgutinflamma\on.InahealthygutenvironmentaSOSdeficientstrainisimpairedforcoloniza\onrela\vetoawildtypestrain.Further,inthe presence of acute gut inflamma\on the SOS deficient strain maintains this fitness defect.Significance:MyresultshighlighttheimportanceoftheSOSresponseforE.coliinthemammaliangut.Understandingthemolecularmechanismsgoverningbacterialadapta\onandvirulenceprovidesanewparadigmforcomba\ngbacterialinfec\onsthataimtoimpedepathogenesisandevolu\on.

ResearchGrant:BurroughsWellcomeTrustFundStudentSupport:BurroughsWellcomeTrustFund

� 56

Poster#48

Agene'c-basedvaccineovercomesmaternalan'bodyinhibi'onofimmuneresponses

ElinorWillis,NorbertPardi,KaelaParkhouse,DrewWeissman,andScopE.Hensley

SchoolofVeterinaryMedicine(Willis),DepartmentofMicrobiology,SchoolofMedicine(Willis,Pardi,Parkhouse,Weissman,Hensley),UniversityofPennsylvania,Philadelphia,PA

Infantsarepar\cularlyvulnerabletoinfec\onsandseveredisease,includingfrominfluenzavirus.Oneincreasingly promising strategy to protect them during this period is through maternally derivedimmunity transferred to theneonate.Maternal an\bodies (matAb) canprotect the infant soona}ertransfer but wane over \me, leaving the infant vulnerable again. Therefore, ac\ve immunity viavaccina\onmustalsobegeneratedinthe infant.Here,usingamousemodelweshowthat influenzavirus-specific matAb inhibit the development of infant an\body responses a}er infec\on with liveinfluenzavirusorvaccina\onwithinac\vatedvirus.However,anovelmRNA-basedvaccineexpressingan influenza virus protein was able to generate strong an\body responses in mice that possessedinfluenza virus-specific matAb, leading to long-las\ng protec\on. This vaccine overcomes matAbinhibi\on through long-terman\genexpressionand sustainedgerminal centerac\vityanddoesnotrequire cell-surface an\gen expression. Together, these results suggest that gene\c vaccines canovercomematAbinhibi\onandelicitpotentimmuneresponsesininfants.

Researchgrant:Na\onalIns\tuteofAllergyandInfec\ousDiseases(1R01AI113047,1R01AI108686);Inves\gatorsinthePathogenesisofInfec\ousDiseaseAwardfromtheBurroughsWellcomeFund

Studentsupport:Na\onalIns\tuteofAllergyandInfec\ousDiseases(5-T32-AI055428)

� 57

Poster#49

Transplanta'onofhumanpluripotentstemcell-derivedop'cvesiclesinaratmodelofre'naldegenera'on

AllisonLudwig1,2,JoePhillips2,3,PatrickBarney3,Ka\eBarlow3,LindseyJager3,BethCapowski3,DavidGamm2,3,4.

1DepartmentofCompara\veBiomedicalSciences,UniversityofWisconsin,Madison,WI;2McPhersonEyeResearchIns\tute,UniversityofWisconsin,Madison,WI;3WaismanCenter,UniversityofWisconsin,Madison,WI;4DepartmentofOphthalmologyandVisualSciences,UniversityofWisconsin,Madison,WI

Photoreceptor(PR)deathisaleadingcauseofblindnessworldwide,andfewtreatmentop\onscurrentlyexistforaffectedpa\ents.However,humanpluripotentstemcell(hPSC)-derivedre\nalorganoidshaverecentlyemergedasasourceofphotoreceptorsfordevelopingcell-basedtherapiesforblindingre\naldiseases.Ourworkisthereforefocusedonevalua\ngstemcell-basedPRreplacementtherapyintheFoxn1-S334terrat,amodelofre\naldegenera\on.UsingahPSC-CRX+/tdTomatoreporterlineandtheGammlab’spreviouslydescribedprotocolfordifferen\a\on,re\nalorganoidsweregeneratedandtransplantedintothesubre\nalspaceofadultratswithdegeneratere\nas.Eyesfromtransplantedratswereassessedat1,3,and6monthspost-transplantforrodandconedifferen\a\on,hostbipolarcelldendri\coutgrowth,andsynapseforma\on.Anatomicevidenceofintegra\onincludinghostbipolarcellsprou\ngandsynap\cproteinexpressionwaspresentasearlyas2weekspost-transplant.By6months,hPSC-derivedphotoreceptorsdominatedthehPSC-deriveddonorcellpopula\onintheFoxn1-S334terratsubre\nalspace,manyofwhichexpressedmaturerodandconemarkers,andprolifera\vere\nalprogenitorcellswereataminimum.Assuch,transplanta\onofhPSC-derivedre\nalorganoidshasthepoten\altoreconstructthephotoreceptorlayerfollowingseverehostphotoreceptordegenera\onandfurtherstudiesoftransplantsafetyandefficacyinrodentmodelsarewarranted.

ResearchGrant:ThisworkwassupportedbytheFounda\onFigh\ngBlindnessWynn-GundTRAP(Transla\onalResearchAccelera\onProgram)Award,Re\naResearchFounda\on(KathrynandLa\merMurfeeandEmmepA.HumbleChairs),McPhersonEyeResearchIns\tute(SandraLemkeTroutChair),CarlandMildredReevesFounda\on,NIHP30HD03352,MuskingumCountyCommunityFounda\on,ChoroideremiaResearchFounda\on.

StudentSupport:StudentsupportwasprovidedbytheUniversityofWisconsin-MadisonDVM/PhDTrainingProgram.

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Poster#50

Analysisofbiotransforma'onofenvironmentalbladdercarcinogensbycanineglutathioneS-transferases

Authors:K.R.Luethcke,J.Ekena,andL.A.Trepanier

Affilia'ons:DepartmentofMedicalSciences,SchoolofVeterinaryMedicine,UniversityofWisconsin-Madison,Madison,WI.

Transi\onalcellcarcinomaofthebladder(TCC)hasbeenassociatedwithcertainenvironmentalchemicalexposuresinbothhumansanddogs.GlutathioneS-transferases(GSTs)areimportantbiotransforma\onenzymesforreac\veenvironmentalchemicals,andpolymorphismsaffec\ngthefunc\onofGSTsfromthemu-,pi-,andtheta-classeshavebeenassociatedwithTCCriskinhumans.DogsalsohavepolymorphicGSTmu(GSTM1)andpi(GSTP1)isoforms,andtwopolymorphicGSTthetaisoforms(GSTT1andGSTT5).However,itisnotknownwhichcanineGSTsareimportantfordetoxifica\onofenvironmentalchemicalsthathavebeenassociatedwithTCCrisk.Theaimofthisstudyistoiden\fywhich,ifany,GSTisoformsindogscatalyzethebiotransforma\onofcompoundsfromfivecategoriesofcandidateenvironmentalbladdercarcinogens,includingacrolein,4-aminobiphenyl,sodiumarsenite,4-chlorophenol,andbromodichloromethane.WehypothesizethatoneormorecanineGSTisoformsdetoxifytheseenvironmentalbladdercarcinogens.Anewlyvalidated,generalizableHPLCmethodfordetec\ngglutathionedeple\onwillbeusedtomeasureinvitroglutathione-conjuga\onac\vityofclonedcanineGSTM1,GSTP1,GSTT1,andGSTT5enzymestowardseachcompound.GSTisoformswiththehighestac\vi\esforeachcompoundwillbetestedforeffectsonsubstratemutagenicitycomparedtotheparentcompoundusingamicronucleusassayforDNAdamageincanineurothelialcelllines.Thesedatawillguidethedevelopmentandinterpreta\onoffutureepidemiologicalstudiesinves\ga\ngGSTgene-environmentinterac\onsincanineTCCrisk,andindevelopingchemopreventa\vestrategiesthatmightleveragethisbiotransforma\onpathway.

Researchgrant:MorrisAnimalFounda\onEstablishedInves\gatorGrant

Studentsupport:KRLwassupportedbyNIHNCATSTL1TR000429,UL1TR000427,andTL11TR002375

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Poster#51

EC-specificEphA4abla'onamelioratesBBBdisrup'on,cor'caldamageandfunc'onaldeficitsfollowingTBI

AlisonCash,JohnChen,ElizabethKowalski,XiaWang,andMichelleTheus.

DepartmentofNeuroscience,BiomedicalandVeterinarySciences,Virginia-MarylandCollegeofVeterinaryMedicine,Blacksburg,Virginia.

Disrup\onofthebloodbrainbarrier(BBB)isamajordriverofsecondarydamagefollowingtrauma\cbraininjury(TBI)includingedema,inflamma\on,andexcitotoxicity.AlthoughBBBdysfunc\onisapredic\vemarkerforpooreroutcomesandlong-termdisability,thecellularandmolecularmechanism(s)regula\ngtheBBBfollowingTBIarenotwellunderstood.RecentevidencesuggestsEphreceptors,thelargestfamilyofreceptortyrosinekinases,contributetovariousneurologicalinsults.Usingendothelialcell(EC)-specificEphA4knockout(KO)mice,wefindasignificantdecreaseinBBBdisrup\oncomparedtowild-type(WT)miceat6hours,1day,and4dayspost-TBI.Basedonthesefindings,wehypothesizethatEphA4signalingonECsnega\velyregulatesBBBintegrityandneuro-restora\onfollowinginjury.Totestourhypothesisweevaluatedmotorbehaviorat3,7and14dayspost-TBItheneuthanizedthemicetoanalyzebrain\ssuesec\onsusingimmunohistochemistry.OurfindingsindicatethatEC-specificabla\onofEphA4significantlyreduceslesionvolumecomparedtoWTat1,4,and14daypost-CCIinjury.Thiscorrelatedwithasignificantincreaseinmotorrecovery,usingRotarodandbeamwalkassessments.Furtherstudieswilladdressthemechanis\croleofEphA4onBBBdisrup\on,includingthebi-direc\onalcommunica\onbetweenECsandastrocytesintheneurovascularniche.Thisdataprovidesevidenceofanovelnega\veregulatoroftheECresponsefollowingTBIthatmaybeexploitedfortherapeu\cpurposes.

ResearchGrant:ThisworkwassupportbytheNIH;NINDSR01NS096281(MHT)StudentSupport:Virginia-MarylandRegionalCollegeofVeterinaryMedicinedualdegreeprogram

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Poster#52

Neutrophillocaliza'onandinterac'onsinthespleenofamousemodelofsystemiclupuserythematosus

Authors:CatharineR.Cowan,RujuanDai,MichaelEdwards,BeqnaHeid,S.AnsarAhmed

Affilia'ons:DepartmentofBiomedicalSciencesandPathobiology,Virginia-MarylandCollegeofVeterinaryMedicine,VirginiaTech,Blacksburg,VA

Abstract:SystemicLupusErythematosus(SLE)isacomplexautoimmunedisorderthataffectshumans,canines,andrarelyfelinesandequines.SLEmanifestswithaconstella\onofclinicalsignsandisdrivenbyan\gen-autoan\bodycomplexdeposi\on.Itisgenerallythoughtofasanadap\veimmunesystemdisease,howeverrecentworkhaselucidateddysregula\onoftheinnateimmunesystemaswell.Neutrophilsaretheprimaryinnateimmunedefendersagainstpathogensandarecommonlyshort-livedandrapidlyrecruitedtositesofinflamma\on.Recentstudieshavedemonstratedsignificantplas\cityintheirbehavior,par\cularlyinSLE.NeutrophilnumbersareincreasedinthespleenofSLEpa\entsandSLEmousemodels,andtheseneutrophilssecretecytokinessuchasBAFFandIL-17thatcanregulateBandTcellfunc\onaswellasactinanautocrinefashion.NeutrophilsarefoundinboththemarginalzoneandTcellzoneofthewhitepulp,withvariablelocaliza\ondependingonthemodelanddiseasecourse.Weareinves\ga\ngpoten\alaltera\onsinthephenotypeandfunc\onofsplenicneutrophilsintheMRL/MpJ-FaslprSLEmousemodel.WehavefoundincreasednumbersofneutrophilsthatlocalizetotheredpulpandTcellzoneduringac\vedisease.Flowcytometricandimageanalysisofthisneutrophilpopula\onshowsincreasedIL-17andIL-1βexpression,MHC-IIexpression,anddirectinterac\onwithTcells,whileothercanonicalneutrophilfunc\ons(ROSproduc\on,phagocytosis)arenotaltered.Assessmentofneutrophilchemotaxisisongoing.Furtherworkisnecessarytoelucidatetherolethisunusualneutrophilpopula\onplaysinthepathogenesisofSLE.

ResearchGrant:DepartmentofBiomedicalSciencesandPathobiology,Virginia-MarylandCollegeofVeterinaryMedicine

StudentSupport:TheStampsFounda\on,Virginia-MarylandCollegeofVeterinaryMedicine

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Poster#53

Johne’sdisease-inves'ga'onbeyondtheorganism

Authors:AmandaKravitz,RonTyler,NammalwarSriranganathan,PawelMichalak

Affilia'ons:DepartmentofBiomedicalSciencesandPathobiology(Kravitz,Tyler,Sriranganathan),VirginiaMarylandCollegeofVeterinaryMedicine,VirginiaTech,Blacksburg,VA;EdwardViaCollegeofOsteopathicMedicine(Michalak),Blacksburg,VA

Abstract:Johne’sdisease(JD),causedbyMycobacteriumaviumsubsp.paratuberculosis(MAP),isachronicinflammatoryintes\naldiseaseofwildanddomes\cruminantsworldwide.Infec\onresultsinsevereweightloss,diarrhea,anddecreasedmilkproduc\on.IntheUnitedStatesthisdiseasehasdevasta\ngeconomicimpact,es\matedat$200millionannually.Currentlytherearenovaccines,treatments,orcontrolstrategiescapableofpreven\ngdisease,dueinpart,toalackofunderstandingthemechanismsofprotec\veimmunity.Genomewideassocia\onstudies(GWAS)haveiden\fiedresistanceassociatedpolymorphismsinNucleo\de-bindingoligomeriza\ondomain-containingprotein2(NOD2),Solutecarrierfamily11member1(SLC11A1),andVitaminDreceptor(VDR)genes.TheproductsofNOD2,SLC11A1,andVDRgenesfunc\ontogetherintheinnateimmuneresponsetoMycobacteria,andthuspolymorphismsinthesegenescanpoten\allyinfluencethehostresponsetoinfec\on.Ourlabhasiden\fiedapoten\allyresistantbreedofsheeporigina\ngfromTamilNadu,southernIndia.Althoughdiagnos\callyposi\veforJD,uponnecropsytheseanimalslackedbothgrossandhistopathologicalcharacteris\csofdisease.Wehypothesizethatsuscep\blesheepwillexhibitincreasedgranulomasandpathologicaldamagecharacteris\cofJDcomparedtoresistantsheep.

ResearchGrant:VirginiaMarylandCollegeofVeterinaryMedicineStudentSupport:DVM/PhDdualdegreesupport

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Poster#54

RoughBrucellaexpressingGnRHandFSH:Anovelbrucellosisimmunocontracep'onvaccine

Waldrop,S.G.,Smith,G.P.,Jane-Gupta,NBoyle,S.M.,Sriranganathan,N.

Department of Biomedical Sciences and Pathobiology at the Virginia-Maryland College ofVeterinaryMedicineatVirginiaTech,Blacksburg,VA.

Whilebrucellosishasbeeneradicatedfromdomes\clivestockintheUnitedStates,thecausa\veagentiss\llpresentinelk,bison,andferalswine.Theinterac\onbetweeninfectedwildlife,domes\clivestock,andhumansposesagreathealthrisk.Ofpar\cularconcern,feralswinepopula\onshavequadrupledinthepasttenyearsandcon\nuetoexpandna\onwide.Feralswineareknowncarriersofbrucellosisandotherzoono\cdiseaseslikeleptospirosis,pseudorabies,E.coliO157:H7,andswineinfluenza.Thecurrentpopula\oncontrolprac\ceshaveneitherminimizedtheirspreadnortheconserva\ve$1.5billiondollarsofdamageayeartoagriculturetheycause.Thereisaneedtoefficientlycontroltheferalswinepopula\onandpreventthespreadofzoono\cdiseases,likebrucellosis,todomes\cfoodanimalsandul\matelythepublic.TworoughstrainsofBrucella(B.abortusRB51andB.neotomae)expressinggonadotropinreleasinghormone(GnRH)and/orfollicles\mula\nghormone(FSH)havethepoten\altobeaneffec\veimmunocontracep\veforferalswinemanagement,whilereducingthespreadofbrucellosis.Thesestrainscouldpavethewayfornoveleffec\veimmunocontracep\vetoolstobeusedinwildlifeanddomes\canimalhealthmanagement.

StudentsupportisprovidedbytheVMCVMResearchandGraduateStudiesdepartment.

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ListofPar'cipants

CombinedDegreeStudents

DylanAmmons dyammons@colostate.edu ColoradoStateUniversity

ElliopChiu elliop.chiu@colostate.edu ColoradoStateUniversity

CaitlinDaimon cmdaimon@colostate.edu ColoradoStateUniversity

KristenDavenport kristen.a.davenport@gmail.com ColoradoStateUniversity

EnriqueDoster Edoster@colostate.edu ColoradoStateUniversity

DilaraKiran dilara.kiran@colostate.edu ColoradoStateUniversity

Kris\naCeres kc649@cornell.edu CornellUniversity

FrancesChen flc28@cornell.edu CornellUniversity

DavidW.Gludish dwg62@cornell.edu CornellUniversity

KieranKoch-Laskowski klk246@cornell.edu CornellUniversity

EricaLachenauer erl58@cornell.edu CornellUniversity

AmandaLoehr arl244@cornell.edu CornellUniversity

EileenTroconisGonzalez elt55@cornell.edu CornellUniversity

KennedyAldrich aldric68@msu.edu MichiganStateUniversity

ElizabethHaiderer haiderer@msu.edu MichiganStateUniversity

AshleyPutman putmanas@msu.edu MichiganStateUniversity

ZoëWilliams will3084@msu.edu MichiganStateUniversity

AlexanderZaneq zaneq1@msu.edu MichiganStateUniversity

SherryBlackmon sherry.blackmon1@gmail.com MississippiStateUniversity

AcaciaCooper ac1617@msstate.edu MississippiStateUniversity

WilCrosby wbc95@msstate.edu MississippiStateUniversity

JamesNichols jma466@msstate.edu MississippiStateUniversity

BripanySzafran bns267@msstate.edu MississippiStateUniversity

AmandaKortum ankortum@ncsu.edu NorthCarolinaStateUniversity

EmilyMackey emackey@ncsu.edu NorthCarolinaStateUniversity

DanielleMzyk dalindqu@ncsu.edu NorthCarolinaStateUniversity

HannahReynolds hmreynol@ncsu.edu NorthCarolinaStateUniversity

JessicaRomanet jromanet@gmail.com NorthCarolinaStateUniversity

CourtneyRousseSparks carousse@ncsu.edu NorthCarolinaStateUniversity

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AnnieWang cawang@ncsu.edu NorthCarolinaStateUniversity

CourtneyMeason-Smith cmsmith@cvm.tamu.edu TexasA&MUniversity

JennCossaboon jcossaboon@ucdavis.edu UniversityofCaliforniaDavis

ChaseGarcia cagar@ucdavis.edu UniversityofCaliforniaDavis

KaqHorng krhorng@ucdavis.edu UniversityofCaliforniaDavis

DevanMurphy devmurphy@ucdavis.edu UniversityofCaliforniaDavis

HarmanpreetPanesar hkpanesar@ucdavis.edu UniversityofCaliforniaDavis

AyswaryaSundaram asundaram@ucdavis.edu UniversityofCaliforniaDavis

JenniferBloodgood jcbloodg@uga.edu UniversityofGeorgia

JacqulineRisalvato jcprisalvato@uga.edu UniversityofGeorgia

HunterOppler opple001@umn.edu UniversityofMinnesota

EmilyPope popex102@umn.edu UniversityofMinnesota

GabrielleRobbins robbi264@umn.edu UniversityofMinnesota

JaclynCarlson jaclynca@upenn.edu UniversityofPennsylvania

MeganClark clarkmeg@vet.upenn.edu UniversityofPennsylvania

PierceNathanson piercen@vet.upenn.edu UniversityofPennsylvania

BrinkleyRaynor bhraynor@vet.upenn.edu UniversityofPennsylvania

AmandaSamuels mandiesamuels123@gmail.com UniversityofPennsylvania

ElinorWillis elwill@vet.upenn.edu UniversityofPennsylvania

AllisonLudwig aludwig4@wisc.edu UniversityofWisconsin-Madison

RosLuethcke luethcke@wisc.edu UniversityofWisconsin-Madison

HannahMar\n Hlmar\n4@wisc.edu UniversityofWisconsin-Madison

AlisonCash amcash3@vt.edu VirginiaMarylandCVM

CatharineCowan crc3d@vt.edu VirginiaMarylandCVM

AmandaKravitz akravitz@vt.edu VirginiaMarylandCVM

GrantWaldrop stevenw3@vt.edu VirginiaMarylandCVM

VeterinaryStudents

MichaelaBops bopsm@uoguelph.ca UniversityofGuelph

EmilyCli}on emily.cli}on25@uga.edu UniversityofGeorgia

ShereeDeadrick sndeadrick@gmail.com UniversityofGeorgia

AlexaDiaz alexa.diaz@uga.edu UniversityofGeorgia

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EricErwood eerwood3@uga.edu UniversityofGeorgia

JohnGorzynski jgorz@stanford.edu StanfordUniversity

KevinMora kemor22@gmail.com UniversityofGeorgia

VictoriaTrutwin vrt02941@uga.edu UniversityofGeorgia

JuliaWalton julia.walton@uga.edu UniversityofGeorgia

Speakers

TheresaAlenghat theresa.alenghat@cchmc.org UniversityofCincinnaq

ErinChu chu.erin@gmail.com EmbarkVeterinary,Inc

JenniferKishimori jennifer.m.kishimori.mil@mail.mil USArmy

TimKurt tkurt@founda\onfar.org Founda\onforFoodandAgricultureResearch

RoxannMotroni Roxann.motroni@ars.usda.gov USDAAgriculturalResearchSta\on

StephanieMurphy stephanie.murphy@nih.gov NIH,Div.Compara\veMedicine

NoelleNoyes Noelle.Noyes@colostate.edu ColoradoStateUniversity

Faculty&Sponsors

TedMashima tmashima@aavmc.org AAVMC

VictoriaMcGovern vmcgovern@bwfund.org BurroughsWellcomeFund

Jus\nLee jus\n.lee@colostate.edu ColoradoStateUniversity

SusanVandeWoude Sue.Vandewoude@colostate.edu ColoradoStateUniversity

HeleneMarquis hm72@cornell.edu CornellUniversity

MistyTreanor mcarder@iastate.edu IowaStateUniversity

QijingZhang zhang123@iastate.edu IowaStateUniversity

RhondaCardin rcardin@lsu.edu LouisianaStateUniversity

VilmaYuzbasiyan-Gurkan vygsu@msu.edu MichiganStateUniversity

SusanEwart ewarts@cvm.msu.edu MichiganStateUniversity

LindaMansfield mansfie4@cvm.msu.edu MichiganStateUniversity

KathrynMeurs kate_meurs@ncsu.edu NorthCarolinaStateUniversity

PatrickGreen green.466@osu.edu TheOhioStateUniversity

MicheleMorscher morscher.1@osu.edu TheOhioStateUniversity

MichaelOglesbee oglesbee.1@osu.edu TheOhioStateUniversity

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RobertCBurghardt rburghardt@cvm.tamu.edu TexasA&MUniversity

MikeCrisci\ello mcrisci\ello@cvm.tamu.edu TexasA&MUniversity

DanaGaddy dgaddy@cvm.tamu.edu TexasA&MUniversity

RogerSmithIII rosmith@cvm.tamu.edu TexasA&MUniversity

LarrySuva lsuva@cvm.tamu.edu TexasA&MUniversity

XinbinChen xbchen@ucdavis.edu UniversityofCaliforniaDavis

HarryDickerson hwd@uga.edu UniversityofGeorgia

KelseyHart khart4@uga.edu UniversityofGeorgia

SusanSanchez ssanchez@uga.edu UniversityofGeorgia

JenniferSmith-Garvin jgarvin@uga.edu UniversityofGeorgia

SusanMWilliams smwillia@uga.edu UniversityofGeorgia

LoisHoyer lhoyer@illinois.edu UniversityofIllinois

MarkRutherford ruthe003@umn.edu UniversityofMinnesota

MichaelAtchison atchison@vet.upenn.edu UniversityofPennsylvania

MichaelMay maym@vet.upenn.edu UniversityofPennsylvania

JenniferPunt punt@vet.upenn.edu UniversityofPennsylvania

LindaFrank lfrank@utk.edu UniversityofTennessee

StephenKania skania@utk.edu UniversityofTennessee

DaleBjorling dale.bjorling@wisc.edu UniversityofWisconsin-Madison

Charles(Chuck)Czuprynski czuprync@vetmed.wisc.edu UniversityofWisconsin-Madison

JennyDahlberg jenny.dahlberg@wisc.edu UniversityofWisconsin-Madison

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