Embed Size (px)
Citation preview
Dr. Gregory Ordway, Interim Chair Department of Biomedical Sciences With the recent completion of our annual mandatory laboratory inspections, it should remind us all that one of the main priorities within the Department of Biomedical Sciences is to ensure a safe working environment for all employees. This is particularly important for those employees who dedicate their time and effort within the laboratories. Many thanks to all laboratory personnel for their assistance in ensuring the laboratories are in compliance with Radiation Safety and Environmental Health & Safety Rules and Regulations. A special thank you is extended to Rolf Fritz and TJ Neal for assisting in this process by conducting preliminary lab inspections in Buildings119 and 178. The Department of Biomedical Sciences offers several opportunities throughout the year for participation in Seminar activities. This extracurricular activity is designed as a means to expose Faculty and Students to the varied research opportunities within the Department. Attendance at seminars conducted by external speakers is especially important. A good attendance reflects well on us as an educational institution. Let us work together to enhance and improve our Seminar opportunities—and to grow professionally. James H. Quillen College of Medicine Department of Biomedical Sciences P. O. Box 70582 Johnson City, TN 37614 423-439-6346
www.etsu.edu/com/dbms
BioMed Highlights A Newsletter of the Department of
Biomedical Sciences James H. Quillen College of Medicine
TJ Neal—Editor
October 2013
INSIDE THIS EDITION
►Publications
►Grant Awards
►Presentations
►Faculty News
►Student News
►Staff News
►Seminar Information
►Abstracts
Please submit news and information to TJ Neal -
Creating and/or Producing Your Research Posters
Creating and/or Producing Your Poster through the
Department of Biomedical Communications—Check
out this website for pricing, types, and order
instructions:
http://www.etsu.edu/com/biomedcomm/documents/
Page 2 DBMS - News & Events
Publications Agrawal, A. Not only immunoglobulins, C-reactive protein too. Mol. Immunol. 56: 561-562, 2013. Frazier, A. and S. Champney, Inhibition of ribosomal subunit synthesis in Escherichia coli by the vanadyl ribonucleoside complex. (2013) Curr. Microbiol. 67 (2): 226-233.
Hoover, D.B., Girard, B.M., Hoover, J.L. and Parsons, R.L. PAC1 receptors mediate positive chronotropic responses to PACAP-27 and VIP in isolated mouse atria. European Journal of Pharmacology 713:25-30, 2013. Rodgers, W., Ashley D. Frazier and W. Scott Champney. Solithromycin Inhibition of protein synthesis and ribosome biogenesis in Staphylococus aureus, Streptococcus pneumoniae, and Haemophilus influenzae. (2013) Antimicrobial Agents Chemother. 57 (4): 1632-1637. Fox SJ, Shelton BT, Kruppa MD. Characterization of Genetic Determinants That Modulate Candida albicans Filamentation in the Presence of Bacteria.PLoS One. 2013 Aug 7;8(8):e71939. doi: 10.1371/journal.pone.0071939. eCollection 2013. Agrawal, A. Not only immunoglobulins, C-reactive protein too. Mol. Immunol. 56: 561-562, 2013.
Leonard, C.A., Schell, M., Schoborg, R.V. and J.R. Hayman. (2013) “Encephalitozoon intestinalis infection increases host cell mutation frequency. Infectious Agents and Cancer. (In Press).
New Grants Awarded - Congratulations!
Cholinergic Anti-inflammatory Response to Vagal Stimulation in Polymicrobial Sepsis”; Greater Southeast Affiliate of the American Heart Association; Grant-in-Aid; Donald B. Hoover, P.I.; Cherie Bond and Tammy Ozment, CIs; project funding period 07-01-2013 to 6-30-2015; $150,000 direct and $15,000 indirect for entire budget period. Total Award: $165,000.
“Bringing the power of whole genome analysis to ETSU.” ETSU RDC; Michelle M. Duffourc, P.I.; Interdisciplinary Grant; project funding period 07-01-2013 to 6-30-14; Total Award: $50,000. This grant will be used to purchase a next generation sequencer and provide training to ETSU personnel.
“Evaluation of vagal nerve stimulation (VNS) for treatment of heart failure.” Cyberonics, Inc. Jeffrey Ardell, P.I.; J. Andrew Armour, Eric Beaumont and E. Marie Southerland (Co-Investigators); project funding period 07-01-2013 to
06-30-2015; Total Award: $808,649.
“Lgr5-expressing cells in taste papillae: Role in adult taste cell regeneration.” ETSU RDC Major Grant; Theresa Harrison, P.I., project funding period 07-01-2013 to 06-30-2014. Total Award: $10,000. “Purification and isolation of extracytoplasmic vesicles (exosomes) from the opportunistic pathogen Candida albicans”; ETSU RDC-14-017M; Michael Kruppa, P.I.; project funding period 07-01-2013 to 06-30-2014; Total Award: $6,780. “Understanding protein abnormalities that control DNA and genetic integrity in prematurely-aging progeroid cells.” ETSU RDC; Phil Musich, P.I.; project funding period 07-01-2013 to 6-30-2014; Total Award: $10,000.
“ Zebrafish embryos as a model system to investigate how brain chemicals such as serotonin effect the machinery for movement.” ETSU RDC; Paul Monaco, P.I.; project funding period: 07-01-2013 to 6-30-2014; Total Award:
$9,000.
Pu
blic
atio
ns
/Gra
nts
Page 3 DBMS - News & Events
Faculty Presentations
Hoover, D.B., Bond, C.E., Ozment, T.R., McDonald, D., Williams, D.L. “Molecular evidence for upregulation of the cholinergic anti-inflammatory phenotype during sepsis.” Oral presentation given at the 36
th Annual Conference on Shock, June 1-4,
2013, San Diego, CA.
Meng-Yang, Zhu, M.D., Ph.D Oral presentation given at the Internal Medicine Research Seminar Series, VA Campus, July 23, 2013, Johnson City, TN.. “Effects of Chronic Social Defeat and Glucocorticoids on Norepinephrine Transporter Expression and Underlying Molecular Mechanisms.”
Dr. R M Kostrzewa, made an oral presentation on “Evolution of Selective Neurotoxins” at the Neurotoxicity Society satellite meeting for the 11th International Symposium on VIP, PACAP and Related Peptides in Pécs, Hungary, 26-31 August 2013.
Dr. R. M. Kostrzewa, Professor, Chaired the symposium: “Dopamine D2 receptor supersensitivity: impact on schizophrenia” and made the oral presentation “Dopamine D2 receptor supersensitization – effect on dopamine release and actions” in this session at the 11th World Congress of Biological Psychiatry in Kyoto Japan, 23-27 June 2013.
Dr. Gregory Ordway, was an invited seminar speaker at the Ohio State University College of Pharmacy, October 17, 2013, The title of his talk was, "Advanced Aging of Oligodendrocytes in Depression and Suicide."
HEART-BRAIN RESEARCH RETREAT—ROAN MOUNTAIN STATE PARK
The 2nd Annual Heart-Brain Research Retreat was held at Roan Mountain State Park, Tennessee, October 8-10, 2013. The theme of the retreat was: “Recent Advances in Neurostimulation Therapy—Emergence of New Horizons.” The retreat was co-sponsored by Cyberonics and the Laboratory of Dr. Jeffrey Ardell. The Roan Mountain State Park provided attendees a positive and scenic environment in which to share and actively
participate in discussions in experimental findings and to “explore emerging hypotheses regarding anatomy, physiology and neuromodulation therapies that promise to improve the lives of patients struggling with the burden of serious disorders such as epilepsy and heart failure.” “The research collaboration between East Tennessee State University and Cyberonics has yielded important new findings that rapidly improve our understanding of complex neural control system behavior of acute and chronic heart failure. These advances promise to accelerate adoption and shape future clinical practice.” - Jeff Ardell (ETSU) & Bruce KenKnight. (Cyberonics) (Pictures from retreat on following page). Presenters at Heart-Brain Research Retreat: Dr. Jeffrey Ardell presented a talk on “Foundations of Neurocardiology:Therapeutic Implications.”
Dr. Jeffrey Ardell presented a talk on “Autonomic Regulation Therapy (ART):Afferent & Efferent Interactions Mediated Within the Cardiac Nervous System.”
Dr. Eric Beaumont presented a talk on “Autonomic regulation Therapy (ART) for Cardiac Disease: Effects on Intrinsic Cardiac Neuronal Function.” Dr. Donald Hoover presented at talk on “Neuroanatomical Organization of Peripheral Ganglia.” Dr. Gregory Ordway presented a talk on “Thoracic Spinal Cord Stimulation Protects the Hippocampal Dentate Gyrus from Heart Failure-Induced Neural Damage.” Dr. Gary Wright presented a talk on, “Chronic Autonomic Regulation therapy (ART) at the level of the Myocyte: Stress-Signaling and Metabolism.
Fa
cu
lty P
res
en
tatio
ns
22ndnd
AnnualAnnual HeartHeart--Brain Research Retreat Brain Research Retreat
October 8October 8--10, 201310, 2013 Roan Mountain State Park, TennesseeRoan Mountain State Park, Tennessee
Page 4
Page 5 DBMS - News & Events
Research Collaborations in The Netherlands
Dr. Dennis Defoe and Dr. Terry Harrison conducted collaborative research at the laboratory of Dr. Hans Clevers, University of Utrecht, The Netherlands, September 26-October 15, 2013. Dr. Clevers is a renowned expert in adult stem cell biology and cancer. He is the former Director of the Hubrecht Institute (The Netherlands Institute for Development and Stem Cell Research); and, currently head of the Netherlands Academy of Arts and Sciences. While there, Dr. Defoe and Dr. Harrison participated in research using a new mutant mice model to investigate the identity and cell biology of stem cells responsible for ongoing regeneration of the taste sensory cells in lingual taste buds.
Students present at the 15th Annual Midwest DNA Repair Symposium, May 18-19 in Lexington, KY
Ben Hilton received the 1st place prize for graduate student platform presentation: “Molecular Mechanisms of Genome IInstability in Hutchinson-Gilford Progeria Syndrome.” Benjamin Hilton, Yiyong Liu, Hui Tang, Steven Shell, Youjie Wang, Ji Liu, Phillip Musich, Antonio Rusinol, Michael Sinensky, and Yue Zou. This material also was presented as a poster at The Progeria Research Foundation Scientific Workshop in Bethesda, MD, April 24–26, 2013. Undergraduate and graduate students presenting posters at the Midwest DNA Repair Symposium:
“DNA synthesis, repair and cellular senescence in aging progeroid cells.” Henry M Gong and Phillip R Musich “A Novel Structural Insight into XPA-DNA Interaction.” Benjamin Hilton, Nick Shkriabai, Steven Shell, Phillip Musich, Walter Chazin, Mamuka Kvaratskhelia and Yue Zou “Cytoplasmic ATR lacking checkpoint kinase activity is a Bax-inhibiting anti-apoptotic protein at mitochondria.” Zhengke Li, Phillip Musich, Benjamin Hilton, Moises Serrano, Hui Wang, Nikolozi Shkriabai, Mamuka Kvaratskhelia and Yue Zou. “Neurotoxin DSP4 induces persistent DNA damage in noradrenergic cells.” Yan Wang, Phillip R. Musich, Moises A. Serrano, Yue Zou and Meng-Yang Zhu
Service Committee Assignments
Dr. Alok Agrawal, Professor, has been invited to serve on the NIH-III (Innate Immunity and Inflammation) Study Review Committee, October 3-4, 2013, National Harbor, MD.
Dr. Michelle Duffourc, Associate Professor, has been appointment to serve as a member of the College of Medicine Medical Student Education Committee.
Dr. Jennifer Hall, Assistant Professor, has been appointment to serve as a member of the College of Medicine Medical Student Education Committee.
Dr. Mitchell Robinson, Professor and Associate Dean for Graduate Studies, has been appointed to serve a three-year appointment on the ETSU Graduate Council. Dr. Meng-Yang Zhu, Professor, has been appointed to serve as a member of the College of Medicine’s Promotion and Tenure Committee.
Upcoming Conferences/Workshops
November 9-13, San Diego, CA
November 16-20, 2013, Dallas, TX
Page 6 DBMS - News & Events
Dr. Fred Hossler, Professor
Emeritus—Still working on research
and book publishing.
Dr. Barbara Turner, Professor
Emeritus—Chaplain at
Johnson City Medical Center.
Dr. Michelle Duffourc, Associate Professor, received The American Society for Pharmacology and Experimental Therapeutics “Pharmacology Education Award.” Presented by Robert J. Theobadd, Ph.D., Division for Pharmacology Education Committee Member. Only two individuals are honored with this award annually.
“Dear W. Scott Champney: Since its online
publication on Jan 15, 2008, there has been a
total of 8694 chapter downloads for your book
on SpringerLink, our online platform…. this
means your book was one of the top 50% most
downloaded eBooks in the relevant Springer
eBook Collection in 2012.”
Springer for Authors
Dr. Gregory A. Ordway, Interim Chair, was bestowed the DISTINGUISHED FACULTY AWARD FOR RESEARCH, at the ETSU Faculty Convocation held on August 23, 2013. During the awards ceremony Dr. Ordway received a plaque, medallion, and a monetary award. CONGRATULATIONS to Dr. Ordway for receiving this most prestigious and deserving honor.
Dr. Ronald Baisden, Professor
Emeritus—Relaxing and enjoying
his music.
FEATURED - RECENTLY RETIRED COM FACULTY — “Life After Academics”
Page 7 DBMS - News & Events
DEPARTMENT OF BIOMEDICAL SCIENCES RECENT
PHD GRADUATES—CONGRATULATIONS!
CORY A. LEONARD, Presented her Dissertation Defense on July 1, 2013. Title of Research: Microsporidia Adherence and Infection of Host Cells In Vintro.” Cory accepted a Postdoctoral Position in the laboratory of Dr. Nicole Borel at the Institute of Veterinary Pathology, University of Zurich, Zurich Switzerland. She will be working on
bacterial pathogen Chlamydia research.
MOISES ALEJANDRO SERRANO, Presented his Dissertation Defense on June 21, 2013. Title of Research: Novel Roles of Replication Protein A Phosphorylation in the Cellualr Response to DNA Damage.” Moises is a Fellow of Clinical Cytogenetics Program at University of Utah.http://www.path.utah.edu/education/fellowships/fellows/moises-a-serrano-ph-d/
ELIOT T. SMITH, Presented his Dissertation Defense on July 1, 2013. Title of Research: “Bioengineering the Expression of Active Recombinant Human Cathepsin G, Enteropeptidase, Neurophil elastase, and C-Reactive Protein in Yeast.” Eliot is pursuing a postdoctoral position with a focus on gaining experience in industry in the short term (e.g. life sciences, pharmaceutical, or biotech company).
SEAN J. FOX, Presented his Dissertation Defense on July 2, 2013; Title of Research: “Identification and Characterizations of Genetic Factors Involved in Candida-Bacterial Interactions.” Sean is an Instructor with ETSU’s Department of Health Sciences. In addition to coordinating all of the undergraduate laboratories for the department, he is also responsible for developing new courses and opportunities that emphasize undergraduate research and novel student research projects.
ZHENGKE LI, Presented his Dissertation Defense on August 8, 2013. Title of
Research: “New Insights into the Roles of Human DNA Damage Checkpoint
Protein ATR in the Regulation of Nucleotide Excision Repair and DNA Damage-
induced Cell Death, He accepted a Postdoctoral Fellow position at the University
of California Medical School.
SEAN J. FOX
CORY A. LEONARD
MOISES ALEJANDRO SERRANO
ELIOT T. SMITH
ZHENGKE LI
Page 8 DBMS - News & Events
Regenia Beth Phillips Campbell
Candidate for the Degree of Doctor of Philosophy in Biomedical Sciences
Department of Biomedical Sciences
October 28, 2013
Dissertation Abstract
Arrested and Aberrant: Effects of Amoxicillin in a Murine Model of Chlamydial Infec-tion
Chlamydia trachomatis is the most common sexually transmitted bacterial disease agent worldwide, and, though frequently asymptomatic, can cause extreme pathology including infertility. Chlamydial species exhibit a unique biphasic developmental cycle. Once attached to a cell surface, infectious elementary bodies (EB) are internalized within an inclusion, the membrane-bound struc-ture in which EB transform to non-infectious, replicable reticulate bodies (RB). After multiple rounds of division, RB condense to form EB, which are released and can infect new host cells. In culture, exposure to stressors, such as beta-lactam antibiotics, induce chlamydiae to reversibly detour from normal development into a non-infectious, viable state termed persistence. Cell culture data suggest that persistent forms are resistant to azithromycin (AZM), a front-line antibiotic, and are able to alter the host transcriptome. Though persistence has been described in culture for over 50 years, wheth-er or not it: i) occurs in vivo; and ii) influences chlamydial pathogenesis, transmission and therapy has remained unresolved. To address these questions, we developed an animal model of persistent chlamydial infection using amoxicillin (AMX) treatment. AMX exposure decreased shedding of infec-tious chlamydiae in C. muridarum-infected mice without affecting chlamydial viability, demonstrating the presence of persistent chlamydiae. Shedding of infectious EB resumed following AMX cessa-tion. Shedding data and microarray analyses suggested that host immunity might limit chlamydia’s exit from persistence in our model. Thus, we hypothesized that cyclophosphamide (CTX) treatment would increase the magnitude of chlamydial shedding observed after AMX-treatment cessation. CTX treatment increased post-AMX shedding by more than 10-fold compared to AMX-only controls. To determine whether persistent chlamydiae are resistant to antibiotic eradication in vivo, we in-duced persistence by administering AMX and treated mice with various AZM dosing regimes. Per-sistently infected mice demonstrated increased treatment failure following AZM therapy compared to productively infected controls. These data suggest that persistent chlamydiae are refractory to treat-ment in vivo and provide an explanation for the observation that treatment fails in some patients. In addition to creating the first fully characterized, experimentally tractable, in vivo model of chlamydial persistence, these experiments provide evidence that persistent/stressed chlamydial forms may serve as a long-term reservoir of infectious organisms in vivo.
Page 9 DBMS - News & Events
Toh Boniface Gang
Candidate for the Degree of
Doctor of Philosophy in Biomedical Sciences Department of Biomedical Sciences
October 30, 2013
Dissertation Abstract
Mechanisms of the Anti-pneumococcal Function of C-Reactive Protein
Human C-reactive protein (CRP) increases survival of and decreases bacteremia in mice infected with Streptococcus pneumoniae. Such protection of mice against pneumococcal infection is seen only when CRP is administered into mice 6 hours before to 2 hours after the injection of pneu-mococci, but not when CRP is given to mice at a later time. Our first aim was to define the mechanism of CRP-mediated initial protection of mice against infection. It was proposed that CRP binds to phosphocholine moieties present in the cell wall and ac-tivates the complement system on the pneumococcal surface, leading to the killing of the pathogen. We generated a CRP mutant F66A/T76Y/E81A incapable of binding to phosphocholine. Mutant CRP did not protect mice from pneumococcal infection. Thus, the proposed hypothesis was correct; the phosphocholine-binding property of CRP contributes to the protection of mice against pneumococcal infection. Our second aim was to investigate why CRP was not protective during the late stages of in-fection. Pneumococci are known to recruit an inhibitor of complement activation, factor H, from the host to their surface to escape complement attack. We considered the ability of CRP, in its non-native form, to bind to factor H, and generated a CRP quadruple mutant E42Q/F66A/T76Y/E81A capable of binding to factor H. In vivo experiments using the CRP quadruple mutant are in progress. We antici-pate that the combination of wild-type and quadruple mutant CRP should be protective during the late stages of infection; wild-type CRP would bind to phosphocholine and activate complement while mu-tant CRP would cover factor H to prevent its complement-inhibitory activity. Our long-term goal is to explore the possibility of developing a CRP-based strategy to treat pneumococcal infection.
Page 10 DBMS - News & Events
Justin Michael Beach
Candidate for the Degree of
Doctor of Philosophy in Biomedical Sciences Department of Biomedical Sciences
November 1, 2013
Dissertation Abstract
An Examination of the Inhibitory Effects of Antibiotic Combinations on
Ribosome Biosynthesis in Staphylococcus Aureus
Bacteremia initiated by Staphylococcus aureus infections can be a serious medical problem. Although a number of different antibiotics are used to combat staphylococcal infections, resistance has continued to develop. Combination therapy for certain infections has been used to reduce the emergence of resistance when a single agent has become ineffective. We hypothesize that the use of rifampicin and ciprofloxacin in combination with azithromycin, known for its inhibitory effects on the bacterial ribosome, can create potential synergistic effects resulting from indirect effects on ribosomal subunit synthesis. To determine this, we measured the effects of single and multiple antibiotics on cell growth rates, cell viability, and synthesis rates for DNA, RNA, and protein. We then measured synthesis rates of ribosomal subunits and the amounts of gyrase and RNAP. Effects of the antibiotic combinations on 70S ribosomes was assayed and the amounts of RNA and degradation was measured. We lastly studied the effects of these antibiotic combinations on mutation frequency in Staphylococcus aureus. Our data has shown support not only for the use of antibiotic combination therapy, but has provided strong evidence of an increase in the inhibition of bacterial ribosome assembly in Staphylococcus aureus. The reduction of 50S ribosomal subunit synthesis and 23S ribosomal RNA in cells grown in the presence of azithromycin, already known for it’s inhibitory effects on the 50S subunit synthesis, in combination with rifampicin or in combination with rifampicin and ciprofloxacin was observed. This also resulted in a reduction or elimination in the frequency of resistant cells when grown in the presence of these combinations. These studies have shed light on the mechanism of action involved and synergistic effects occurring in combination antibiotic treatments and how ribosomal subunit assembly is affected. The insights gained through this research provide necessary information needed for the design of more potent antibiotic combinations. This will create a better understanding and new methods for eliminating the spread of harmful pathogens such as Staphylococcus aureus.
Page 11 DBMS - News & Events
Students Participate in Summer Research Opportunities:
The Department of Biomedical Sciences provided valuable research opportunities for students during
the Summer of 2013. Opportunities were supported through the National Science Foundation (NSF), Honors
College, and AHA Medical Student Summer Research Fellowships. The Faculty Sponsors are to be
commended for donating their expertise towards this valuable opportunity and for their dedication to the future
of science.
Student University/School Hometown Supported By Faculty Sponsor
Sarah Ardell Science Hill H.S.
Johnson City, TN
Johnson City, TN Dr. Ferslew Dr. Ferslew
Alexander Blume Warren Wilson College,
Swannanoa, NC
Vorhees, NJ NSF-REU Dr. Harrison
Rees Burt ETSU, Johnson City, TN Bristol, TN ETSU Honors Col-
lege
Dr. Wondergem
Lucas Cantwell Assumption College,
Worcester, MA
Plymouth, MA NSF-REU Dr. Hoover
Julia Colgrove ETSU, Johnson City, TN Kingsport, TN ETSU Honors Col-
lege
Dr. Schoborg
Stephanie Cunningham Biomedical Sciences
Graduate Student, Johnson
City, TN
Kingsport, TN Dr. Singh Dr. Singh
Hannah Frye ETSU, Johnson City, TN Apopka, FL American Physiologi-
cal Society
Dr. Ecay
Henry Gong ETSU, Johnson City, TN Bristol, TN Dr. Musich Dr. Musich
Saghar Harirfaroosh Emory University,
Emory, VA
Johnson City, TN Dr. Singh Dr. Singh
Kaitlyn Hinshaw ETSU, Johnson City, TN Boone, NC Dr. Thewke Dr. Thewke
Ariella Jackson University of Alabama
Birmingham, AL
Birmingham, AL NSF-REU Dr. Ecay
Taylor Johnson University of Pikeville,
Pikeville, KY
Big Rock, VA NSF-REU Dr. Hoover
Zach Lahr ETSU
Johnson City, TN
Bluff City, TN
Dr. Thewke Dr. Thewke
Jonathan Millard
ETSU
Johnson City, TN
Bristol, TN Dr. Singh Dr. Singh
Elizabeth Stone University of North Carolina,
Wilmington, NC
North Kingston, RI NSF-REU Dr. Defoe
Gregory Wiessner Gustavus Aldophus College
of Sweden
Bloomington, MN NSF-REU Dr. Ecay
WELCOME…. Stephanie Cunningham
Ms. Stephanie Cunningham is our newest Graduate Student in the Department of Biomedical
Sciences. Stephanie has been a volunteer within the lab of Dr. Krishna Singh, Professor, since
January 2013. Her hometown is Commack, New York (Long Island). Currently she resides in
Kingsport, TN. Stephanie holds a B.A. Degree in Political Science from the State University of
New York at Oswego (Class of 2011) and certification in New York State EMT. As a Graduate
Assistant, Stephanie will continue working with Dr. Singh (Advisor).
Page 12 DBMS - News & Events
Medical Students Participate in Summer Research Opportunities:
Medical Student Sponsored By Faculty Sponsor
Aaron Ashe AHA Summer Research Exposure Program Dr. Beaumont
Caryn Brehm AHA Summer Research Exposure Program Dr. Musich/Zou
Ben Cearlock AHA Summer Research Exposure Program Dr. Thewke
Nathan Davis AHA Summer Research Exposure Program Dr. Szebeni/Ordway
Jason Fleenor AHA Summer Research Exposure Program Dr. Wright
Chris Hill AHA Summer Research Exposure Program Dr. Zhu
Ben Cearlock AHA Summer Research Exposure Program Dr. Thewke
Nathan Davis AHA Summer Research Exposure Program Dr. Szebeni/Ordway
Jason Fleenor AHA Summer Research Exposure Program Dr. Wright
Chris Hill AHA Summer Research Exposure Program Dr. Zhu
Good Job… If you have good news,
we want to pass it on.
Chris Millsaps, former RSO at U.T. Knoxville, was onsite 6/7/13 to perform our annual Radiation Safety Program
audit. The audit is required to determine if we are effectively meeting the requirements of our Radioactive Materi-
als License and The State of Tennessee Regulations for Protection Against Radiation (SRPAR). Chris did not
identify any areas of non-compliance during his inspection. “
Janice Lyles, Radiation Safety Officer
East Tennessee State University
“I want to commend both TJ Neal and Rolf Fritz for their hard work and determination in preparing the Biomedical
Science department for this inspection. This is the largest inspection that we perform as there were over 45 labor-
atories to inspect and found each of them to be managed in a compliant and orderly manner. To inspect this
many laboratories and find only recommendation type actions is exemplary. Thank you for your continued compli-
ance.”
Mike Barrett
Manager, Environmental Health and Safety
East Tennessee State University
“Robin (Montgomery). If I haven’t told you before, I greatly appreciate the work that you do to keep our accounts
in order. Thank you so much for the monthly e-mails and the printouts. It really helps keep things in order. “
Dr. Sharon Campbell
Department of Biomedical Sciences
This is the notification of recognition of Angela’ Thompson’s attention to detail in catching the delivery charges for
the gases to the entire university community. “Airgas will be deducting all delivery charges to invoices associated
with industrial gas deliveries to ETSU. The delivery charges on the invoices were a mistake. Thank you.”
Lesia Pendelton
Purchasing Agent
East Tennessee State University
Page 13 DBMS - News & Events
We extend our thanks and appreciation to Ms. Cindy Canter, Coordinator, for serving
as our Staff Senate representative. During her tenure as a Staff Senator, Cindy represented the
College and Department in a professional and exemplary manner. Cindy’s dedication has been
embedded in the College of Medicine for more than 30 years. Her professionalism, outgoing
personality, and enthusiasm reflects in everything that she does. We commend Cindy and
appreciate her endeavors in this role.
Again, Thank you, Cindy, for your years of dedicated service as Staff Senator for the
College of Medicine, and especially for the Department of Biomedical Sciences.
Brigitte Browe was accepted into the Department of Biological Sciences Ph.D. program for Fall 2013 at the University of Illinois at Chicago, with a concentration in Neurobiology. In the 2013 U.S. News & World Report's ranking of colleges and
universities, UIC ranked as the 147th best national university. The Times Higher Education World University Rankings ranked UIC as the 11th best in the world among universities less than 50 years old. Brigitte’s employment with ETSU/COM began in the Department of Anatomy in May 2009 as the Laboratory Coordinator, She remained an integral part of the Department of Biomedical Sciences until her departure at the end of July 2013. CONGRATULATIONS are extended to Brigitte on this professional achievement. Our well wishes are extended to her as she pursues her doctoral degree in the “Windy City.”
Best Wishes and Congratulations! Jim and Tonya Ward on the marriage of their daughter, Brittany.
Jacob and Brittany Adkins were married on August 17, 2013, in an outdoor setting at Eldridge Farm in Jonesborough/Johnson City, TN. Pictured on the right is Tonya’s youngest daughter, Erin. Once
again, Congratulations Tonya!
(Good News—Cont’d) “TJ, You absolutely must let your facility know that Thermo Fisher is very impressed and thankful for your efficiency. Not many labs let us know when changes like this happen. Usually we have to go around and around trying to find out data like this. Seems simple and is but usually just does not happen. Please let them know that It was allowed to put a $50 discount in both of these contracts for this year due to your help. Trust me TJ, you are an exception to the rule for most loca-tions. We do very much appreciate your way of doing things! Please see the attached revised quotes for renewal.” Randall Russell Service Sales Specialist Uniity Lab Services Part of Thermo Fisher Scientific
Page 14 DBMS - News & Events
WELCOME…. Dr. Maoxian Deng
Dr. Deng obtained his doctorate in Environmental Health
(Environmental Health & Molecular Toxicology) at Sichuan University,
West China Center of Medical Sciences. He completed postdoctoral
training and experience at Fudan University, Shanghai, and
Universities of Cincinnati and Pennsylvania. Dr. Deng has joined the
laboratory of Dr. Meng-Yang Zhu, located in Stanton-Gerber Hall.
WELCOME…. Emily Yang
Ms. Yang obtained her Masters in Clinical Pharmacology from Wannan
Medical College, Wuhu, Anhui Province of the P.R.C. Fanny’s work
experience includes training at the Pharmacology and Natural Medicine
Laboratory of Wannan Medicine College, and Innomed Scientific
Incorporation Limited as the Engineer in the Department of R&D. She
has joined the laboratory of Dr. Meng-Yang Zhu, located in Stanton-
Gerber Hall.
WELCOME…. Robert “Rob” M. Becker, Jr.
Rob joined the Department of Biomedical Sciences as Laboratory
Coordinator. He is a graduate of ETSU with a B.S. in Psychology/
Neuroscience and a minor in Biology. Rob previously served as an
Intern in the Department and assisted in the operations of the Anatomy
Page 15 DBMS - News & Events
ETSU PRIDE WEEK CONTEST
August 20-21, 2013
Crystal Maupin’s Enthusiasm Reflected During ETSU Pride Week
“President Noland and Madam First Lady, I share the attached with you as evidence of at least one highly motivated Buccaneer on this side of the street. You should see Crystal’s office in person. It’s amazing. This is real Buccaneer spirit and her kind of pride is hard to beat! It lives and its contagious!!! … She still gets her work done and does it well. That too is real Buccaneer spirit. Thought you would be interested..” Doug Taylor, Assistant Dean Admissions and Records Quillen College of Medicine
“I think the most fitting response (and a very educational one...) is WOW! Thank you for sharing the photos and please pass a long my sincere appreciation of her efforts. That is absolutely phenomenal! “ Donna Noland ETSU First Lady
Montgomery Participates in Carter County Leadership Tomorrow Program
Robin Montgomery, Financial Management Analyst, has been selected as the ETSU Representative for the Carter County Leadership Tomorrow Program Class of 2013-2014. Robin is responsible for the management of all state-funded accounts for the Department of Biomedical Sciences. She holds a Bachelor of Science degree in Accounting and a Master of Business Administration (MBA) degree from ETSU. Robin is a resident of Elizabethton, Carter County, Tennessee. The Leadership program is sponsored by the Elizabethton/Carter County Chamber of Commerce. Mission of the program is to identify, encourage, and develop individuals who have a sincere appreciation for Elizabethton and Carter County, demonstrate potential leadership skills, and are willing to accept leadership roles to ensure a positive future for Carter County. Goals of the program are to: create a core of committed leaders; develop a long term vision for the community; learn more about the citizens and the issues; create a network of community relationships among Leadership graduates. Some of the subjects to be covered during the program include: Regional Leadership, Healthcare, Local Government, Business and Industry, Education, Heritage, State Government, and Federal Government. Robin was nominated for the position by Cynthia Taylor who is an Alumni of the Carter County Leadership Tomorrow Program.
Page 16 DBMS - News & Events
The ANNUAL COM HALLOWEENIEHALLOWEENIEHALLOWEENIE ROAST
held on October 28, 2013, was enjoyed by
many COM employees and students!
(Dr. Caroline Abercrombie pictured above in
Witch Costume)
Congratulations to the following winners!!
Cindy Canter
SCARIEST PUMPKIN
Dr. Caroline Abercrombie
MOST ORIGINAL PUMPKIN
Dr. Cherie Bond
FIRST PLACE—SCARIEST COSTUME
Dr. Caroline Abercrombie
SECOND PLACE—SCARIEST COSTUME
Community Service Projects
Generosity—the quality of being kind and
generous.
Thanksgiving Food Drive
It is time for the Annual Thanksgiving Food Drive for those in need. Be checking your pantry for canned goods and non perishable food items. Also, please consider a monetary donation which is greatly needed—even a small donation will help. Contact person:
Cindy Canter, 439-2000.
Christmas Angel Project
It is almost time for the Annual Christmas Angel. Monetary donations accepted any time. Contact person: Tonya Ward, 439-2001.
Annual Coat Drive
Donations are being accepted for the Annual Coat Drive. Please look for collection boxes located in hallway.
Cell Phone Donations
Remember to donate your used cell phones. Collection boxes are located in the buildings.
Recycling
Remember to donate your plastic bags to the “Bags to Benches” recycling program. A collection box is located in Stanton-Gerber Hall on the Ground Floor. Contact Person: Bobbie Connelly at 439-2053.
Help the Animal Shelter
Donations to the Animal Shelter are always needed.
Page 17 DBMS - News & Events
DEPARTMENT OF BIOMEDICAL SCIENCES SEMINAR SERIES
PRESENTS
DR. CHARLES CALDWELL
ASSOCIATE PROFESSOR: TRAUMA, SEPSIS, AND INFLAMMATION RESEARCH GROUP
DEPARTMENT OF SURGERY, UNIVERSITY OF CINCINNATI
OCTOBER 28, 2013
ABSTRACT
"THE GENERATION AND IMPACT OF NEUTROPHIL DERIVED MICROPARTICLES
DURING SEPSIS"
During sepsis, exquisite control of inflammation is necessary to execute beneficial actions (bacterial clearance) while minimizing pathogenesis. Initially, activated leukocytes participate in the anti-microbial response. During sepsis, leukocytes can undergo apoptosis or become unresponsive. In other inflammatory models, both activated and apoptotic leukocytes have been shown to be precursors to microparticles (MPs). MPs are small vesicles of heterogeneous density and composition. The role of MPs in sepsis is currently poorly characterized. Our novel preliminary data demonstrate that neutrophil-derived MPs (NDMPs) are increased during sepsis, decrease survival and can increase immune suppression. This is important as there is an ongoing paradigm shift concerning our understanding of sepsis. Whereas early, uncontrolled inflammation was a prevailing therapeutic target in the past, recent reports have increased awareness of immune paralysis later during sepsis leading to difficulty clearing bacteria or fungus. Altogether, this talk will summarize our efforts to understand how NDMPs are generated and their impact using a murine model of sepsis.
Page 18 DBMS - News & Events
S.O.S. (Sharing of Science)
Monthly Research Roundup meetings are underway!
Monthly volunteers are needed for the monthly S.O.S. talks held each month.
Please contact Dr. Mike Kruppa, Seminar Committee Chair, now to schedule a date.
Thank you.
The Biochemical Nature of Disease Journal Club
meets at noon each Thursday and is a brown bag lunch.
Interested individuals should contact Dr. Sharon
Campbell to schedule a presentation time.
Speaker Schedule for Biochemistry of Disease—
Date Speaker
September 26 Scott Champney
October 3 Jessica Crawford
October 10 Phil Musich
October 17 Doug Thewke
October 24 Annie Wang
October 31 David Hurley
November 7 Ben Hilton
November 14 Aashish Morani
November 21 Yue Zou
November 28 THANKSGIVING HOLIDAY
December 5 Fidelis Ikeweme
December 12 Martha Borketey
DBMS SEMINAR SERIES
Important Notice!!
The Biomedical Sciences Seminar Committee is
soliciting suggestions for seminar speakers.
Please provide
suggestions and Email of
individuals, along with a
brief summary of their
research, to Dr. Mike
Kruppa: [email protected]
Microbiology Journal Club — Meets Alternating Thursdays at 9 a.m.—Year round except holidays.
Faculty Contact: Dr. Robert Schoborg.
Pharmacology Graduate Students Journal Club — Meets Mondays at 3:30 pm, Building 1, Room B06.
Faculty Contact: Dr. Don Hoover.
Page 19 DBMS - News & Events
The foyer in Building 1 now reflects a warm and inviting atmosphere thanks to the interior designing skills of Mary Lou Hawk. The once drab, lifeless, and uninviting area now exudes with “new life” vibrancy and a professionally-designed look. Other personnel in the building are taking notice as well and are saying “Thank You” to Mary Lou for a job well done. Also, many thanks to Dr. Rob Schoborg for the donation of the framed landscape print that now accentuates the two side chairs in the foyer!
Foyer in Building 1 Receives “New Life”
Page 20 DBMS - News & Events
ABSTRACTS—2ND ANNUAL HEART-BRAIN RESEARCH RETREAT
Foundations of Neurocardiology: Therapeutic Implications
Jeffrey L. Ardell, PhD FAHA
Neurons in the intrinsic cardiac and intrathoracic extracardiac networks of the cardiac nervous system form separate and distinct nested feedback loops that act in concert with central feedback loops in the spinal cord, medulla and higher centers to coordinate regional cardiac function. Intrathoracic ganglia contain afferent, local circuit (interneurons) and sympathetic efferent postganglionic neurons. Cardiac-related parasympathetic efferent postganglionic neurons are confined to the intrinsic cardiac ganglia. These networks, in turn, are modulated by circulating neurohumoral agents such as angiotensin II and catecholamines. Imbalances in cardiac neurohumoral control, especially those leading to excessive efferent neuronal activation, are associated with adverse short- and long-term alterations in cardiac function - including cardiac arrhythmia induction and pump failure. Thus, the cardiac neuronal hierarchy has emerged as a novel therapeutic target for managing cardiac disease via pharmacological, physical and /or electrical means. Stabilization of imbalances within select elements of the cardiac neuronal hierarchy can reduce the arrhythmogenic potential in both atrial and ventricular tissues, can maintain myocyte viability and thus prolong survival, while at the same time maintaining regulatory function.
Autonomic Regulation Therapy (ART): Afferent & Efferent Interactions Mediated within the Cardiac
Nervous System Jeffrey L. Ardell, PhD FAHA
Electrical stimulation, delivered at various nexus points of the cardiac neuronal hierarchy, evokes changes in the central and peripheral neuronal function as manifest by activation of both afferent and efferent projections. The neuronal (and cardiac) effects of such electrical stimuli dependent upon: 1) the characteristics of the imposed stimulus (and fiber types so activated); 2) the endogenous neuronal response to such novel activity and 3) long-term adaptations to such chronic stimuli. Higher-frequency (20-30 Hz) low amplitude vagal nerve stimulation (VNS) differentially impacts central neural function; lower frequency (10 Hz) moderate intensity (1.5-2.5 mAmp) VNS represents the
autonomic engagement threshold (AET) where functional suppressive effects on regional cardiac
function are manifest. Following rostral transection of the cervical vagosympathetic trunk, AET to VNS is reduced even when the contralateral vagus is cut. Likewise, VNS impacts ICN neuronal function at intensity levels below those sufficient to modify basal cardiac function. In addition, the ICN sub-serves sympathetic-parasympathetic interactions at sites separate from the end-effector. Finally, VNS stabilizes ICN responses to imposed neural imbalances, thereby reducing the arrhythmogenic potential and maintaining adequate pump function. Together, these data indicate the preeminent information processing capabilities mediated within the peripheral aspects of the cardiac nervous system and its dynamic control of regional cardiac function.
Autonomic Regulation Therapy (ART) for Cardiac
Disease: Effects on Intrinsic Cardiac Neuronal Function
Eric Beaumont, PhD
Myocardial infarction and chronic hypertension are associated with adverse remodeling of the intrinsic cardiac neurons. Specifically, the electrical properties of intrinsic cardiac neurons, their sensitivity to neurotransmitters as well as the efficacy of the synaptic transmission between them are altered. This specific neuronal plasticity, in part, contributes to the progression into heart failure. Chronic ART using cervical vagal nerve stimulation, concurrently activates afferent neurons projecting into the central nervous system and efferent neurons projecting into the visceral organs. When delivered concurrently with induced cardiac diseases (e.g. myocardial infarction or pressure overload), ART impacts individual neuronal and network function within the intrinsic cardiac nervous (ICN) system. Cardiac disease-induced remodeling in the electrical properties of individual neuron and the efficacy of synaptic transmission within the ICN are mitigated with ART. Preservation of ICN function by ART is likewise associated with preservation of contractile function. Since intrinsic cardiac neurons are the final integrator of the cardiac nervous system, neuronal changes elicited by ART represent a significant and under-utilized therapeutic potential slow the progression into heart failure while at the same time maintaining efficacy for integrated reflex response to everyday stressors.
Me
etin
g A
bs
trac
ts
Page 21 DBMS - News & Events
ABSTRACTS—2ND ANNUAL HEART-BRAIN
RESEARCH RETREAT (CONT’D)
Neuroanatomical Organization of Peripheral Ganglia
Donald Hoover, PhD
Autonomic ganglia are important nexuses and integrative centers in the neural circuitry that regulates cardiovascular function. Both the structure and function of these ganglia are more complex than traditionally presented in textbooks. While many neurons of sympathetic and parasympathetic ganglia express markers for their classical neurotransmitters (i.e., norepinephrine and acetylcholine, respectively), these neurons also contain co-transmitters such as neuropeptides or nitric oxide. Additionally, subpopulations of neurons in sympathetic ganglia lack adrenergic markers but express markers for novel neurotransmitters. Some of these non-adrenergic neurons are probably local circuit neurons or afferent neurons. Principal neurons of the autonomic ganglia receive the classical preganglionic cholinergic input, but many of these neurons are also innervated by peptidergic and adrenergic nerve fibers. The output of ganglionic neurons is determined by integration of these diverse inputs. Autonomic ganglia can undergo neurochemical and structural remodeling in cardiovascular disease, and it is likely that such changes contribute substantially to autonomic dysfunction. Preliminary evidence suggests that spinal cord stimulation therapy can reverse remodeling of stellate ganglia in a canine model of heart failure. Beneficial effects of vagal stimulation therapy in heart disease might occur through direct effects on the cardiac nervous system and the cardiomyocytes it innervates. ART may likewise impact the progression of cardiac disease indirectly by modulation of the immune system.
Thoracic Spinal Cord Stimulation Protects the Hippocampal Dentate Gyrus from Heart Failure-
induced Neural Damage Gregory Ordway, PhD
Background: Myocardial infarction (MI) and progression into heart failure (HF) is associated with pathological changes in the central nervous system. We previously demonstrated in a canine model of MI and mitral regurgitation (MR) that thoracic spinal cord stimulation (SCS) reduces mortality and preserves
autonomic responsiveness for control of cardiac function. The purpose of this study was to evaluate potential protective effects of SCS in the brain in MI/MR. Methods: Canines (n=14) underwent HF model creation involving sequential inductions of MI and MR; eight canines served as sham controls. MI/MR animals were randomized to two arms: “Control” with SCS OFF (N=8) and SCS (T1-T5, 50 Hz, 200 µsec, 90% motor threshold) starting one week post MR induction (n=6). Both groups were maintained for 12 weeks post MI/MR induction. Autonomic status was evaluated for cardiac control prior to termination, after which brains were surgically removed. The hippocampus was isolated and evaluated using histochemistry (Nissl staining) and gene expression analysis of caspase-3, e-NOS and NMDAR NR1 subunit. Cell density in the dentate gyrus (DG) was assessed using ImageJ software to measure the area fraction of cell bodies using Nissl-stained sections. Results: Nissl staining revealed visual evidence of gross neuronal pathology in the hippocampus of MI/MR dogs. Upon detailed examination, we found that the area fraction of neuronal cell bodies within the DG was significantly reduced in MI/MR as compared to sham control dogs. SCS mitigated the neural damage in the DG, maintaining cell density at levels equivalent to sham controls. MI/MR was associated with significantly elevated levels of caspase-3 and eNOS gene expressions. SCS significantly reduced or abolished increases of caspase-3 and eNOS gene expression induced by MI/MR in the hippocampus. Gene expression of the NR1 subunit (a marker of neuronal birth/death) of the NMDA receptor was increased in MI/MR, whereas SCS reduced NR1 gene expression in the MI/MR dogs to sham control levels. Conclusion: Thoracic SCS exerts neuroprotective effects within the hippocampus in the setting of chronic HF. SCS-mediated neuroprotection may be mediated by SCS-induced inhibition of apoptosis. SCS also reverses the effects of MI/MR on a marker of neurogenesis. Collectively, these findings demonstrate that SCS modulates multiple signaling pathways in the brain that are adversely affected by
heart failure.
Me
etin
g A
bs
trac
ts
Page 22 DBMS - News & Events
ABSTRACTS—2ND ANNUAL HEART-BRAIN RESEARCH RETREAT (CONT’D)
Chronic Autonomic Regulation Therapy (ART) at the Level of the Myocyte:
Stress-Signaling and Metabolism Gary Wright, PhD
Electrical stimulation at various points within the cardiac neuronal hierarchy has emerged as a novel therapeutic approach for addressing cardiac disease. Specifically we have found that vagal nerve stimulation, at frequencies and currents below those that result in overt effects on cardiac function, confer beneficial effects upon the biological sequelae of infarct and pressure overload stress in heart. Accordingly, the signaling pathways and metabolic alterations affected by ART at the level of the myocyte are of interest in understanding the mechanisms through which ART exerts its effects. The finding that vagal nerve stimulation, subsequent to a coronary artery ligation, significantly increases the phosphorylation status of glycogen synthase (GS) has broad implications for myocyte glucose metabolism. Because GS is a substrate for upstream cardioprotective signaling pathways, the finding may also reflect ART effects upon stress-signaling kinases. Consistent with this notion, ART is observed to change the levels of apoptosis-related regulatory proteins and the phosphorylation status of GSK-3β, a pivotal cardioprotective signaling kinase which resides upstream of GS. Collectively the data indicate that ART exerts potent modulatory effects upon metabolic rearrangements associated with the cardiac disease through specific signaling pathways associated with the myocyte stress-response.
ABSTRACTS—INTERNAL MEDICINE RESEARCH SEMINAR PROGRAM
Effects of Chronic Social Defeat and Glucocorticoids on Norepinephrine Transporter
Expression and Underlying Molecular Mechanisms.
Meng-Yang Zhu, M.D., Ph.D.
Both chronic stress and deficiency of central noradrenergic transformation have been considered to be related to the etiology of major depression. Also, stress and related stress hormones have been reported to activate the brain noradrenergic system. However, the molecular link between chronic stress and noradrenergic neurons remains to be elucidated. This presentation illustrated: 1) Using animal model, the chronic social defeat upregulated expression of the norepinephrine transporter in the brain locus coeruleus and its main terminal regions, which is mediated by glucocorticoid receptors. 2) The similar regulation has been observed in the intact rats that have been chronically treated with oral corticosterone to mimic stressful status. 3) In vitro study to identify cis-acting DNA sequences in NET promoter demonstrated that an interaction between glucocorticoids and transcription factor C/EBP-β, through a C/EBP-β response element, positively controls transcription of NET genes. The present findings indicate a correlation between chronic stress and activation of the noradrenergic system, which may act on the gene promoter via a nonconventional transcriptional mechanism. This correlation and CSD-induced alteration in signal transduction molecules may account for their critical effects on the development of symptoms of major depression.
Mee
ting
Ab
stra
cts
