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Santosh Kumar, Ph.D. July 2014 1 CURRICULUM VITAE NAME: SANTOSH KUMAR, Ph. D. DATE: 07/2014 h-index: 19 i-10-index: 29 CURRENT POSITION AND ADDRESS Associate Professor Department of Pharmaceutical Sciences College of Pharmacy University of Tennessee Health Science Center 881 Madison Ave. Memphis, TN 38163 Phone: 901-448-7157 (off) Phone: 409-370-1664 (cell) Email: [email protected] EDUCATION 06/1998 Ph. D. Biotechnology, Biotechnology Center, Indian Institute of Technology (IIT), Bombay 400076, India 06/1993 M. S. Biotechnology, Biotechnology Center, IIT, Bombay 400076, India 01/1991 B. S. Chemistry, ARSD College, University of Delhi, New Delhi 110021, India PROFESSIONAL APPOINTMENTS UTHSC 06/2008 - Current Associate Professor, Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Cet UMKC 09/2008 - 06/2008 Assistant Professor, Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City (UMKC) Prior to UMKC 03/2008 - 08/2008 Assistant Research Scientist, Department of Pharmacy and Pharmaceutical Sciences University of California San Diego, San Diego, CA 92093 06/2005 - 02/2008 Research Assistant Professor, Department of Pharmacology and Toxicology, University of Texas Medical Branch (UTMB), Galveston, TX 77555 08/2002 - 05/2005 Research Instructor, Department of Pharmacology and Toxicology, UTMB, Galveston, TX 77555 07/1998 - 07/2001 Post-Doctoral Fellow, School of Biological Sciences, (UMKC), Kansas city, MO 64110 PROFESSIONAL DEVELOPMENT UTHSC 1. Special Populations Research Development Seminar Series, National Institute of Drug Abuse, Bethesda, MA, 2013-14: Phase II workshop (mock review of a 12-page R01) on June 26-27.

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Santosh Kumar, Ph.D. July 2014

1

CURRICULUM VITAE

NAME: SANTOSH KUMAR, Ph. D. DATE: 07/2014 h-index: 19 i-10-index: 29 CURRENT POSITION AND ADDRESS

Associate Professor Department of Pharmaceutical Sciences College of Pharmacy University of Tennessee Health Science Center 881 Madison Ave. Memphis, TN 38163 Phone: 901-448-7157 (off) Phone: 409-370-1664 (cell) Email: [email protected]

EDUCATION

06/1998 Ph. D. Biotechnology, Biotechnology Center, Indian Institute of Technology (IIT), Bombay 400076, India

06/1993 M. S. Biotechnology, Biotechnology Center, IIT, Bombay 400076, India 01/1991 B. S. Chemistry, ARSD College, University of Delhi, New Delhi 110021, India

PROFESSIONAL APPOINTMENTS

UTHSC

06/2008 - Current Associate Professor, Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Cet

UMKC

09/2008 - 06/2008 Assistant Professor, Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City (UMKC)

Prior to UMKC

03/2008 - 08/2008 Assistant Research Scientist, Department of Pharmacy and Pharmaceutical Sciences University of California San Diego, San Diego, CA 92093

06/2005 - 02/2008 Research Assistant Professor, Department of Pharmacology and Toxicology, University of Texas Medical Branch (UTMB), Galveston, TX 77555

08/2002 - 05/2005 Research Instructor, Department of Pharmacology and Toxicology, UTMB, Galveston, TX 77555

07/1998 - 07/2001 Post-Doctoral Fellow, School of Biological Sciences, (UMKC), Kansas city, MO 64110

PROFESSIONAL DEVELOPMENT

UTHSC

1. Special Populations Research Development Seminar Series, National Institute of Drug Abuse, Bethesda, MA, 2013-14: Phase II workshop (mock review of a 12-page R01) on June 26-27.

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UMKC

1. Professional Development Conference, Johnson College Community College, May 15, 2009: One day workshop by the experts in the field.

2. FACET Teaching Skills Development Symposium, UMKC, 2010: One day workshop by the experts in the field

3. Non-native Speaking Faculty Workshop by Michael Dix, UMKC, 2011: One day workshop. 4. NIH Grant Writing Workshop by David Morrison, UMKC 2011: One day combined workshop

followed by one-one-one discussion on my R01 grant proposal. 4. Professional Development Conference, Johnson College Community College, May 23, 2012: One

day workshop by expert in the field. 5. Special Populations Research Development Seminar Series, National Institute of Drug Abuse, Bethesda, MA, 2013-14: It was a two day workshop in to promote R01 grant proposal to new

investigators. I presented a R01 concept paper (6- pages) and had one-on-one discussion with two mock reviewers. They selected my project for phase II workshop (mock review of a 12-page R01, Jun e 26-27).

UTMB

1. Teaching improvement project system (TIPS) for health care educators, Sep 2006, UTMB: Two days workshop by UTMB personnel. I received the best teaching assessment as a “Coach”. 2. NIH workshop for grant writing, Oct 2007, UTMB: One Day workshop by NIH personnel.

MEMBERSHIP IN SCIENTIFIC SOCIETIES

UMKC 04/2012 – 03/2013 International Society for Neurovirology (ISNV) 08/2010 - current American Association of College of Pharmacy (AACP) 11/2009 - current Society on NeuroImmune Pharmacology (SNIP) 04/2003 - current American Society for Pharmacology and Experimental Therapeutics (ASPET)

UTMB

03/2003 - 2008 American Society for Biochemistry and Molecular Biology (ASBMB)

HONORS AND AWARDS

UTHSC

08/2014 Faculty Row, The Official Home Of America's Top Faculty™

UMKC

Honors and Awards

05/2014 “Teacher of the Year award” Runner up from the class of 2015, School of Pharmacy, UMKC

12/2013 Mahatma Gandhi Pravasi (Non-resident Indian (NRI)) Samman (Honor). This is presented to 30 NRIs every year to recognize their contribution in the field.

11/2013 Nomination for Burroughs Wellcome Fund for “Investigators in the Pathogenesis of Infectious Diseases”

11/2013 Nomination for Chancellor’s Early Career Award for Excellence in Teaching

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07/2013 Selected to participate in the National Institute on Drug Abuse (NIDA) Special Populations Research Development Seminar Series on September 19-20, 2013 in Bethesda, Maryland

03/2013 Invited as contributing member of ‘FACULTY OF 1000 (F1000)': Invitation accepted

01/2013 Invited to write a book chapter in Industrial Biocatalysis, Pan Stanford Publishing Pte. Ltd., Singapore: Invitation accepted

11/2012 Invited to write a review in Expert Opinion on Drug Metabolism and Toxicology (IF = 3.1): Invitation accepted, manuscript in review

09/2012 Invited to write a review in Mini Reviews in Organic Chemistry (IF = 2.4): Invitation accepted, manuscript in review

08/2012 Invited renowned speaker of a symposium, “HIV-1, Substance abuse, and NeuoAIDS”, 3rd World Congress in Biotechnology, Sep 13-15

07/2012 Editor of special issue entitled: "Cytochrome P450: Drug interactions” for Journal of Drug Metabolism and Toxicology, OMICS publications

07/2012 NIDA/AAPI Travel Fellowship Award, Tobacco/smoking, HIV/AIDS, and Cancer Workshop, 7th Annual Texas Conference on Health Disparities, 2012

06/2012 Editor of special issue entitled: "Enzymatic degradation of environmental pollutants using transgenic plants” for Journal of Petroleum and Environmental Biotechnology, OMICS publications

06/2012 Elected Chair: Early Stage Investigator Committee-Society of NeuroImmune Pharmacology (ESIC-SNIP)

05/2012 NIDA Young Investigator travel award for HIV in the Nervous System and the 11th International Symposium on Neurovirology, 2012

04/2012 Nomination for UMKC Outstanding Faculty Award for iPhD student mentoring 03/2012 Invited to write a review in Expert Opinion on Drug Metabolism and Toxicology

(IF = 3.1) 12/2011 Invited Guest speaker and Co-chair of a symposium, 44th Annual Indian

pharmacological Society Conference (IPSCON), Dec 19-21 08/2011 Invited for Young Investigator Committee-SNIP member 06/2009 Invited to write a review in Expert Opinion on Drug Metabolism and Toxicology

(IF = 3.5) 10/2008 Biography in Who's Who in the World

UTMB

2008 Biography in Who's Who in America 2007 Special invitation to facilitate a problem-based learning (PBL) on Gastro-

intestinal nutrition 2007 Biography in Who's Who in Science and Engineering 2006 Highest score as a Teacher/Facilitator in the category of Instructional set,

Teacher tactics, and Verbal and nonverbal behaviors in a Teaching Workshop 2003 ASPET Drug Metabolism Division Post-doctoral Best Paper Award 1998 Nomination for the Best Thesis Award (The President Gold Medal Award) 1995 Vice-President of SYMBIOTEK (Society for the young member of

Biotechnology), Biotechnology Center, IIT, Bombay - 400076

COMMITTEE

A. National and International

UTHSC (2014 - Current)

Ad-hoc reviewer for many scientific journals

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2014 PLoS ONE

UMKC (2009 - 2014)

03/2013 - current Member: Toxicology section of Pharmacology and Drug Discovery, FACULTY OF 1000 (F1000)

Recommended eight research articles

07/2012 - current Editor: Special issue entitled: "Cytochrome P450: Drug interactions” for Journal of Drug Metabolism and Toxicology, OMICS publications

06/2012 - current Editor: Special issue entitled: "Enzymatic degradation of environmental pollutants using transgenic plants” for Journal of Petroleum and Environmental Biotechnology, OMICS publications

06/2012 – 04/2015 Elected Chair: Early Career Investigator Committee-Society of NeuroImmune Pharmacology (ECIC-SNIP)

Role: 1. Selection for Travel award to attend SNIP meeting: Total applicants: ~75

2. Organization of poster sessions and selection for best poster awards in SNIP meeting: Total posters: ~90

3. Organize and Co-chair of Early Career Investigator Symposium: Total speakers: 6

4. Organize Meet-the-Mentor Lunch: Total attendees: ~140

03/2012- current Executive Editor: Petroleum and Environmental Biotechnology

09/2011 - current Member: Early Career Investigator Committee-Society of NeuroImmune Pharmacology (ECIC-SNIP)

11/2010 - current Associate Editor: The Journal of Drug Metabolism and Toxicology (Open access Bioinfo publications)

07/2010 - current Ad-hoc Editor: Journal of Drug Metabolism and Toxicology, Petroleum and Environmental Biotechnology. (Open access OMICS publication)

01/2011 - current Advisory Editorial Board for International Journal of life Science and Pharma Reviews

03/2011 - current Member: Editorial Board of Pakistan Journal of Scientific and Industrial Research, Series B: Biological Sciences

01/2008 - current Ad-hoc reviewer for many scientific journals

2008 1. Drug Metab. Dispos. (Total 1)

2009 Drug Metab. Dispos. Chem. Res. Toxicol. Protein Eng. Des. Selec. Mol. Biol. Evol. Free Rad. Biol. Med. (Total 5)

2010 Exp. Opin. Drug Metab. Toxicol. Int. J. Neurosci PloS One Alcoholism: Clin. Exp. Res.

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J. Antiv. Antiretrov. Bulletin for Environmental Toxicology J. Amino Acids Bulletin for Environmental Contamination and Toxicology Trends in Biotechnology (Total 9)

2011 Alcoholism: Clin Exp. Res. J. Antiv. Antiretrov. Free Rad. Biol. Med. Pakistan Journal of Scientific & Industrial Research J. Antiv. Antiretrov. Xenobiotica J. NeuroImmune Pharmacology (Total 7)

2012 Current HIV research Drug metabolism letters J. Antiv. Antiretrov. Bull. Environ. Contamin. Toxicol. (2) Int. J. Mol. Sci. Drug Alcohol Dependence Mol. Cell. Biochem. Free Rad. Biol. Med. J. AIDS Clin. Res. Int. J. Mol. Sci. Mol. Cell Biochem. Drug Metab. Dispos. Cancer Lett. (Total 14)

2013 PLOS ONE (4) AIDS Clin. Res. (2) Free Rad. Biol. Med. Enz. Microb. Technol. Frontiers Biosci. Brit. J. Clin. Pharmacol. J. Proteomic Res J. AIDS Clin. Res. Drug Metab. Dispos. Virology Journal Clinical Pharmacology: Advances and Applications 2014 Toxicology and Applied Pharmacology PLoS ONE (2) Molecular Cancer Drug Metabolism and Disposition (2)

UTMB 08/2005 - 2008 Drug Metab. Dispos.

Chem. Res. Toxicol. Arch. Biochem. Biophys. Enz. Microb. Technol. Protein Eng. Des. Selec. Chem. Biol. Interact.

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(Total 6)

GRANT REVIEWER UTHSC (2014 – Current)

1. Institutional Pilot Project Program, Ponce University, School of Medicine 2.

UMKC (2009 - current) 1. American Association of College of Pharmacy (AACP): one grant 2. University of Missouri Research Board (UMRB): two grants 3. National Institute of Health: NeuroAIDS and other end organ diseases

(NAED): 4 grants

UTMB (2007-2008)

4. Austrian Science Fund (FWF): one grant 5. University of Houston Research Council GEAR Grant: one grant

B. UMKC COMMITEES

09/2008 - 08/2009 1. Member, Graduate Program Committee, School of Pharmacy 3. Member, Assessment Sub-committee, School of Pharmacy 2. Member, Research Strategic Committee, Pharmacology and Toxicology

09/2009 - 08/2010 1. Member, Graduate Program Committee, School of Pharmacy 2. Member, School of Pharmacy representative to the Undergraduate Curriculum Committee, UMKC 3. Member, Research Strategic Committee, Pharmacology and Toxicology

09/2010 - 08/2011 1. Member, Graduate Program Committee, School of Pharmacy 2. Member, School of Pharmacy representative to the Undergraduate Curriculum Committee 3. Member, Hazardous Material Oversight, School of Pharmacy

09/2011 - 08/2012 1. Member, Graduate Program Committee, School of Pharmacy 2. Member, Information Technology, School of Pharmacy 3. Member, School of Pharmacy representative to UMKC senator committee (Elected)

09/2012 - 08/2013 1. Member, Graduate Program Committee, School of Pharmacy

2. Member, Research Advisory Council, School of Pharmacy (Elected) 3. Faculty Development Committee 4. Member, School of Pharmacy representative to UMKC senator committee (Elected)

09/2013 - 08/2014 1. Member, Graduate Program Committee, School of Pharmacy 2. Member, Research Advisory Council, School of Pharmacy (Elected) 3. Member, Information Technology 4. Member, School of Pharmacy representative to UMKC senator committee (Elected) 5. Member, Professionalism 6. Alternate Chair, Honor council (Elected)

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09/2013 - Current Faculty advisor of two Pharmacy students of class of 2017: 1. Yuna Eun, 2. Cecilia Vu

09/2012 - Current Faculty advisor of four Pharmacy students of class of 2016: 1. Kelsi Ezell, 2.

Jonathan Gregory, 3. Tim Miller, and 4. Tuan Vu 08/2012 - 09/2012 Faculty search committee: Clinical Assistant Professor in the Division of

Pharmacy Practice and Administration 11/2012 - Current Faculty search committee: Assistant/Associate Professor in the Division of

Pharmacology and Toxicology 09/2009 - Current 1. Doctoral faculty, School of Pharmacy 2. Graduate faculty, School of Pharmacy

09/2010 - Current Supervisory Committee Member for iPhD Students (Coordinating discipline)

Name Plan of study Comprehensive Thesis Placement

1. Nanda Mandava May 2010 May 2011 Sep 2013 Senior scientist

Pharmacopoeia 2. Sandeep Putty March 2011 Nov 2011 May 2014 Scientist

Bristol-Myer 3. Julia C. Reis May 2011 4. Ashaben Patel May 2011 Dec 2012 Feb 2014 5. Ramya Badlapatla July 2011 April 2012 March 2014 6. Megha Barot Sep 2011 Jan 2012 Jan 2013 Scientist

Pharmacopoeia 7. Mitan Gokulgandhi Sep 2011 May 2012 Aug 2013 Scientist

Pharmacopoeia 8. Mitesh Patel Nov 2011 Dec 2012 9. Ankit Shah Nov 2011 April 2012 Nov 2013 PDF, SOP, UMKC

10. Sudheer Bobba Jan 2012 March 2012 May 2013 Scientist, Covance

Laboratories

11. Ravi Shukla Feb 2012 May 2013 May 2014 PDF,John Hopkins

12. Animikh Ray Aug 2012 Nov 2013 13. Xun Lu Aug 2012 March 2014 14. Jake McQuire Feb 2012 Oct 2012 June 2014 15. Amruta Ronghe Oct 2012 Jan 2014 16. Anwesha Chatterjee Oct 2012 Dec 2013 17. VKC Ponnaluri Nov 2012 Jan 2013 May 2014 PDF 18. Divya T Vavilala Nov 2012 Aug 2013 May 2014 PDF 19. Mohit Gangwani April 2013 June 2014 20. Lu Cao May 2013 21. Anantha Nookala Sep 2013 22. Harika Vemula Nov 2013 23. Wei Jin Dec 2013 Five students have graduated.

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09/2009 - Current Chair, Supervisor/Mentor of iPhD Students from Pharm/Tox

Name Plan of study Comprehensive Thesis Placement

1. Mengyao Jin May 2011 March 2012 Dec 2012 PDF, UNC- Chapel Hill

2. Anusha Ande Oct 2012

One student has graduated.

C. UTMB

2005 - 2006 1. Supervisory Committee Chair/Mentor for a MS student (Cynthia Hernandez), Graduate School of Biomedical Sciences (GSBS)

2003 - 2007 2. Medical Student Interview Panel, School of Medicine (SOM) 2003 - 2007 3. Summer Medical Student Poster’s Judging Panel, SOM

COMMUNITY SERVIVE

A. Local

06/2011 Seminar/Workshop for High School students titled “Common Drug Metabolism, Clearance, and Toxicity”, School of Pharmacy, UMKC

TEACHING: CLASSROOM

A. UMKC

1. School of Pharmacy

01/2008 - current PHARMACY 7361/5519 (Pharmacology I, Fall and Summer): Team taught course. Summer course includes self-study examinations.

PHARMACY 7362/5520 (Pharmacology II, Spring and Summer): Team taught course. Summer course includes self-study examinations.

Assistant coordinator: Spring 2012 and 2013

Coordinator: Spring 2014

PHARMACY 7463/5509 (Toxicology, Spring): Team taught course

Drug interactions/Adverse reactions, Adrenergic agonists/antagonists, Introduction to chemotherapy, Cell wall synthesis inhibitors, Sulfonamides, Quinolones, Antivirals, Anti-tuberculosis, Antineoplastics, Drugs for Asthma, Thyroid and anti-thyroid drugs, Insulin and Oral hypoglycemics, Dietary Supplements and Herbal Medicine

Credits: ~3/year

01/2008 - Current PHARMA 5616: Methods in Pharmacology and Toxicology

Credits: ~3 (2-3 students/year)

09/2011 - Current Developed, coordinates, and teaches (sole Instructor) a new Elective Graduate and Pharmacy Course: Fall Semester

Pharmacy 5630 Cytochrome P450: Drug Metabolism, Bioavailability, Interactions, and Toxicity (CYP: DMBIT) Credits: 3

01/2013 - Current Pharmacy 7497D Directed individual study for Pharm D students

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1. Bradley Stockard, P3 Pharm D. Spring 2012, Credits: 2 2. Morgan Kohls, P2 Pharm D. Spring 2013, Credits; 2 (scheduled)

Performance evaluation overall score Mandatory Pharmacy and Graduate course: ~155 students Spring 2009 Pharmacology II 4.14/5 Fall 2009 Pharmacology I 4.18/5 Spring 2010 Pharmacology II 4.14/5 Fall 2010 Pharmacology I 4.20/5 Spring 2011 Pharmacology II 4.22/5 Fall 2011 Pharmacology I 4.07/5 Spring 2012 Pharmacology II 4.28/5 Fall 2012 Pharmacology I 4.37/5 Spring 2013 Pharmacology II 4.53/5 Fall 2013 Pharmacology I 4.71/5 Elective Graduate and Pharmacy course: 6-10 students Fall 2011 CYP: DBMIT 4.60/5 Fall 2012 CYP: DBMIT 4.77/5

B. UCSD

1. Skaggs School of Pharmacy and Pharmaceutical Sciences 03/2008-06/2008 Taught Drug metabolism in Pharmaceutical Biochemistry: Drug Target Mechanism.

B. UTMB

1. School of Medicine 2007 - 2008 Taught Cell wall synthesis inhibitors, Sulfonamides, Quinolones in Graduate

Pharmacology Survey Course: Special Topics - PHTX 6000.

2005 - 2007 Facilitated problem-based learning (PBL) courses Gastro-intestinal Nutrition and Cardiovascular and Pulmonary for the 2nd year Medical students.

Performance evaluation overall score 2005: Cardiovascular and Pulmonary: 4.0/5 2006: Gastro-intestinal nutrition: 4.7/5 2007: Gastro-intestinal nutrition: 3.7/5 01/2007 Taught lectures on “Antibiotics and its Pharmacology” for Graduate

Pharmacology Survey Course: PHTX 6000 (ECT-Endo/ Chemo/Tox Pharm).

C. IITB

1995 - 1997 Taught Biochemistry and Enzymology to MS students, Biotechnology Center 1995 - 1996 Taught Biochemistry and Biotechnology to BS students, Dept. of Biotechnology,

V. G. Vaze College of Arts, Commerce & Science, Mulund (E), Bombay

MENTORING/TRAINING: RESEARCH AND SCHOLARSHIP

A. UMKC

Post-doctorate fellows

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1. Ravinder Earla June 2010 - June 2014

2. P.S. Shantanu Rao March 2014 - current

Graduate students (iPhD.)

1. Mengyao Jin (2009-2012): Dean Student Award 2011 Travel Award “Society of NeuroImmune Pharmacology” 2011 Travel Award “Society of NeuroImmune Pharmacology” 2012 Women Council Award 2012

2. Anusha Ande (2011-current): Women Council Award 2012 Best Student of the Year Award 2012 Women Council Award 2013 Dean Student Award 2013 Travel Award “Society of NeuroImmune Pharmacology (SNIP)” 2013 Preparing Future Faculty Scholar Award 2013-14 Travel Award and Plateform Speaker, SNIP 2014

3. Ken McFarlin (2011-current): Richard and Paula Johnson Pharmacy Graduate Student Scholarship 2012

Graduate students in Laboratory Methods course Year Grade 1. Gautham Kodakandla 2013 A 2. Stephani Stancil 2012 A 3. Zhang Yan 2012 A 4. Kshitij Verma 2012 A 5. James Weemhoff 2011 A 6. Ananth Nookala 2011 A 7. Lu Cao 2011 A 8. Mohit Gangawani 2011 B 9. Anusha Ande 2010 A 10. Priyanka Arya 2009 A 11. Xun Liu 2009 B 12. Shruti Kamath 2009 A 13. Amruta Ronghe 2009 B 14. Gautham Rao 2008 B

Research Assistant Year

1. Namita Sinha 10/11 - 05/12

Summer undergraduate students Year

1. Ken Marvin McFarlin 06/11 - 07/11

High school students Year

1. Parnita Harsh 07/13 (three weeks)

B. UTMB

Graduate students (MS)

1. Cynthia Hernandez (2005-2007): Best poster award at 5th SWP450 meeting; second place.

Graduate Laboratory Rotation students Year Grade

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1. Fan Yi 2005 B 2. Robert Malmstrom 2004 A 3. Tori Strong 2004 A

Summer Undergraduate students Year Award

1. Alva Gullstrand 2006 None 2. Yan Larson 2005 Best poster, 1st Place

Joined UTMB for PhD in 2006 3. Jeeba Kuriakose 2004 Best poster, 1st Place

Joined UTMB for PhD in 2005

Post-doctorate fellows (trained) Year

1. Wataru Honma 2005 2. Harshica Farnando 2006 3. Jyothi Talakad 2007

Research Associate (trained) Year

1. Ling Sun 2005

Trained lab personnel

1. Hazard Communication Act 2. Laboratory Safety 3. Radioactive Safety Program

C. UMKC

Graduate laboratory rotation student Year Grade

1. Kanwarjit Singh Chadha (SBS) 2000 A

RESEARCH INTERESTS

A. Alcoholism is highly prevalent in HIV-1-infected individuals. Alcohol consumption is known to enhance HIV-1 replication. In addition, alcohol is known to decrease the response to antiretroviral drugs. However, the mechanism by which these occur is not known. We propose that alcohol-mediated increase in HIV-1 replication occurs through cytochrome P450 (CYP), especially CYP2E1-mediated oxidative stress. Similarly, we propose that alcohol-mediated decrease in response to antiretrovirals occurs through CYP3A4 pathway. Our ongoing project is “Role of cytochrome P450 in alcohol-mediated HIV-1 pathogenesis and antiretroviral therapy”. This project is funded by NIH/NIAAA R01 grant until Aug 2018 (percentile 2).

B. Smoking is highly prevalent in HIV-1-infected individuals. Smoking is known to enhance HIV-1 replication. However, the mechanism by which it occurs is not known. We propose that tobacco-mediated increase in HIV-1 replication occurs through cytochrome P450 (CYP), especially CYP2A6-mediated oxidative stress. Our ongoing project is Tobacco/nicotine, CYPs, and HIV-1. This project is funded by NIH/NIDA R21 grant until April 2014.

C. CYP enzymes are of considerable interest for the: i) synthesis of novel drugs and drug metabolites, ii) targeted cancer gene therapy, iii) biosensor design, and iv) bioremediation. However, their applications are limited because cytochrome P450, especially mammalian P450 enzymes, show a low turnover rate and stability, and require a complex source of electrons through cytochrome P450 reductase and NADPH. Our ongoing projects are Engineering CYP enzymes to study structure-function relationships.

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GRANT SUPPORT

UTHSC: ONGOING

1. Start-up fund: (PI: Kumar, S.) 06/01/2014 - 05/31/2017 $500,000/ 3 years School of Pharmacy, UMKC Title: Cytochrome P450 engineering, drug interactions, alcohol abuse, and HIV-1

2. R01 (PI: Kumar, S. 25% effort) 06/01/2014 - 05/31/2014 $960,000/ 4 years National Institute of Alcohol Addiction and Alcoholism (NIAAA) Title: Role of cytochrome P450 in alcohol-mediated HIV-1 pathogenesis and antiretroviral therapy

UMKC: COMPLETED

1. Start-up fund: (PI: Kumar, S.) 09/01/2008 - 08/31/2012 $250,000/ 4 years School of Pharmacy, UMKC Title: Cytochrome P450 engineering, drug interactions, alcohol abuse, and HIV-1

2. New Investigator Grant: (PI: Kumar, S.) 08/01/2010 - 07/31/2012 $28,000/ 2 year University of Missouri Research Board (UMRB) Title: Effect of Alcohol & HIV Drugs on Cytochrome P450

3. Bridge funding: (PI: Kumar, S.) 10/01/2012 - 09/30/2013 $14,860/ 1 year School of Pharmacy Title: Role of cytochrome P450 in alcohol-mediated HIV-1 pathogenesis and antiretroviral therapy. The funding is to generate additional preliminary data to revise the following scored (29) NIAAA/NIH R01 proposal.

3. R21 (PI: Kumar, S. 20% effort) 05/01/2011 - 04/30/2014 $275,000/ 3 years National Institute of Drug Abuse (NIDA) Title: Tobacco/nicotine, Cytochrome P450, and HIV-1

4. R01 (Co-investigator: Kumar, S. 10% effort) 09/01/12 - 08/31/17 $1,000,000/ 5 years National Institute of Alcohol Addiction and Alcoholism (NIAAA) Title: Alcohol abuse and HIV-mediated neurotoxicity (PI: Kumar, A.)

5. R01 (PI: Kumar, S. 25% effort) 09/01/2013 - 05/31/2014 $1,125,000/ 5 years National Institute of Alcohol Addiction and Alcoholism (NIAAA) Title: Role of cytochrome P450 in alcohol-mediated HIV-1 pathogenesis and antiretroviral therapy

6 Bridge funding: (PI: Kumar, S.) 11/01/2013 - 10/31/2014 $14,881/ 1 year School of Pharmacy Title: Role of cytochrome P450 in tobacco-mediated HIV-1 pathogenesis. The funding is to generate preliminary data to submit a R01 grant to NIDA.

SUBMITTED (Scored and Discussed, but not funded)

1. R03 (PI: Kumar, S.) 04/16/2009 $200,000/ 2 years National Institute of alcohol abuse and alcoholism (NIAAA) Title: Interactions between alcohol and anti-retroviral drugs Priority Score: 280

2. R21 (PI: Kumar, S.) 12/19/2010 $275,000/ 2 years National Cancer Institute (NCI) Title: Engineering CYP2C18 for enhanced cytotoxicity of the anti-cancer prodrug cyclophosphamide Priority Score: 58

3. R01 (PI: Kumar, S.) 10/10/2011 $1,250,000/ 5 years National Institute of Genral Medical Sciences (NIGMS) Title: Examination of the role of E-H helix region in CYP structure-function using alternate approaches Priority Score: 34; Percentile: 31

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4. Investigator in Pathogenesis (PI: Kumar, S. 20% effort) 11/01/2013 $500,000/ 5 years Burroughs Wellcome Fund Title: Cytochrome P450 pathways in tobacco-mediated HIV-1 pathogenesis

UTMB: COMPLETED

1. 05/01/03 – 04/30/04 (Completed): Pilot Grant, ES06676, (PI: Kumar, S.) $10,000/ 1 year

National Institute of Environmental Health Sciences (NIEHS) Center Grant, UTMB, Galveston, TX 77555 Title: Development of a directed evolution approach for mammalian cytochrome P450s

RESEARCH COLLABORATIONS: ONGOING AT UMKC-UTHSC 1. Dr. Anil Kumar, Professor and Chairman, Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City Tel: (816) 235-1792, Email: [email protected] Title: Substance abuse, anti-retroviral therapy, and NeouroAIDS Thirteen publications (S. Kumar: Eight as lead author and five as supporting author) 2. Dr. Ashim K. Mitra, Professor and Chairman, Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City Tel: (816) 235-1615, Email: [email protected] Title: Tobacco, anti-retroviral drugs, and Cytochrome P450 Three publications (S. Kumar: All three as lead author) 3. Dr. Carole McArthur, Professor, Department of Oral Biology, School of Dentistry, University of Missouri-Kansas City Tel: (816) 235-2175, Email: [email protected] Title: Tobacco/Nicotine, Cytochrome P450, and HIV-1 One publication (S. Kumar: As supporting author)

RESEARCH COLLABORATIONS: COMPLETED AT UMKC-UTMB 1. Dr. Leszek Wojnowski, Professor, Institut für Pharmakologie, Johannes Gutenberg-Universität, Obere Zahlbacher Str. Mainz, Germany Tel: (+49) 6131 39 33460, Web-Fax: (+49) 941 5992 36727, E-mail: [email protected] Title: Structural basis of the functional diversity of ancestral and chimpanzee CYP3A4 compared with the human CYP3A4 One publication

2. Dr. Dmitri Davydov, Associate Professor, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, san Diego Tel: (858) 822-7804; Email: [email protected] Title: Cooperativity of bacterial P450eryF Two publications 3. Dr. Mary Moslen-Treinen, Professor, Director Toxicology Program, Department of Pathology and Department of Pharmacology and Toxicology, University of Texas Medical Branch Tel: (409) 772-3650; Email: [email protected] Title: Efficient high performance liquid chromatography/ultraviolet method for determination of diclofenac and 4’hydroxydiclofenac in rat serum One publication

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4. Dr. B. K. Muralidhara, Senior Scientist, Pfizer Inc., PhRD-Global Biologics, St. Louis Tel: (713) 582-4869; Email: [email protected]; [email protected] Title: P450 stability and structure-function using CD, fluorescence, and isothermal titration calorimetry Three publications 5. Dr. Hong Liu, Professor, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Drug Discovery and Design Center, Shanghai, P.R. China; Email: [email protected] Title: Molecular modeling of P450 using protein dynamics and substrate docking Three publications

6. Dr. Werner Braun, Professor, Department of Biochemistry and Molecular Biology and The Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch Tel: (409) 747-6810; Email: [email protected] Title: Identification and structural and functional analyses of conserved sequence motifs in mammalian cytochrome P450 One publication 7. Dr. Dan Rock, Senior Scientist, Pharmacokinetics & Drug Metabolism, Amgen, Seattle Tel: (206) 265-7139; Email: [email protected] Title: Differential time dependent inhibition of P450 3A4 and P450 3A5 by raloxifene: A key role for C239 in quenching reactive intermediates One publication 8. Dr. David J. Waxman, Professor, Department of Biology, Boston University, Tel: (617) 353-7403, Email: [email protected] Title: Engineering of cytochromes P450 2B and 2C for enhanced metabolism of the anti-cancer prodrugs CPA and IFA Three publications

INVITED LECTURES

UMKC

1. Role of cytochrome P450 pathways in alcohol- and tobacco-mediated HIV-1 pathogenesis, School of Pharmacy, Texas Tech Health Science Center, Amarillo, TX, January 12, 2014

2. Role of cytochrome P450 pathways in alcohol- and tobacco-mediated HIV-1 pathogenesis, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, December 16, 2013

3. Role of cytochrome P450 in alcohol-mediated oxidative stress and HIV-1 pathogenesis, The Department of Immunology, Institute of Neuroimmune pharmacology, and Center for Personalized Nanomedicine, Herbert Wertheim College of Medicine, Florida International University, July 18, 2013

4. Role of cytochrome P450 enzymes in tobacco/nicotine-mediated effects on HIV-1 model systems, Symposium: Physiological and Pathological role of nicotinic receptors, Society of Neuroimmune Pharmacology, San Juan, PR, April 3-6, 2013

5. Role of cytochrome P450 enzymes in alcohol-mediated effects on antiretroviral and HIV-1, Division of Pharmaceutical Sciences, School of Pharmacy, UMKC February 12, 2013.

6. Role of cytochrome P450 enzymes in alcolhol-mediated effects on antiretroviral and HIV-1, The Department of Pharmacology, Toxicology &Therapeutics, University of Kansas Medical Center, Nov 20, 2012.

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7. Central role of cytochrome P450 2A6 in tobacco-mediated oxidative stress in maccrophages and astrocytes: implications with HIV-1 pathogenesis and neuroAIDS, Symposium: HIV-1, Substance abuse, and NeuoAIDS, 3rd World Congress in Biotechnology, Hyderabad, India, Sep 13-15, 2012.

8. Central role of cytochromes P450 in alcohol and tobacco-mediated oxidative stress in maccrophages and astrocytes: implications with HIV-1 pathogenesis and neuroAIDS, Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India, Sep 18, 2012.

9. Central role of cytochrome P450 2A6 in tobacco-mediated oxidative stress in maccrophages and astrocytes: implications with HIV-1 pathogenesis and neuroAIDS, Tobacco/smoking, HIV/AIDS, and Cancer Workshop, 7th Annual Texas Conference on Health Disparities, 2012.

10. Central role of cytochromes P450 2A6 in tobacco-mediated oxidative stress in maccrophages and astrocytes: implications with HIV-1 pathogenesis and neuroAIDS, HIV in the Nervous System and the 11th International Symposium on Neurovirology, 2012.

11. Tobacco/alcohol, Cytochrome P450, and HIV-1, Division of Oral Biology, School of Dentistry, UMKC March 07, 2012.

12. Reengineering of Cytochrome P450 for Medicine and Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Dec 23rd, 2011.

13. Tobacco/alcohol, Cytochrome P450, and HIV-1, 44th Annual Conference of Indian Pharmacological Society, Manipal, India; December 19-21, 2011.

14. Role of cytochrome P450 in alcohol/nicotine-mediated oxidative stress and alcohol-antiretrovirals interaction, Division of Pharmacology and Toxicology, School of Pharmacy, UMKC February 03, 2011.

15. Effect of alcohol and antiretroviral therapeutics on cytochrome P450s in macrophages: Relevance to alcoholic HIV-1 patients. Division of Pharmaceutical Sciences, School of Pharmacy, UMKC February 09, 2010.

16. Cytochrome P450-mediated drug interactions and adverse effects, International Conference on Integrative & Personalized Medicine and 42nd Annual Conference of Indian Pharmacological Society, Kolkata, India; December 12, 2009.

17. Conserved sequence motifs as an approach to study structure-function relationships of mammalian cytochromes P450, 8th SWP450 meeting, Camp Allen, Navasota, TX; May 2009.

UTMB

18. Engineering xenobiotic-metabolizing mammalian cytochromes P450 to study structure-function and generating biocatalysts, NIEHS Center Seminar Series at UTMB, Galveston, TX; 2008. (Invited)

19. Designing mammalian cytochromes P450 for enhanced activity and stability. 6th SWP450 meeting, Camp Allen, Navasota, TX, 2007. (Invited)

20. Engineering of xenobiotic-metabolizing mammalian cytochromes P450 using directed evolution. Biotransformation Seminar Series, UTMB, Galveston, TX; 2006. (Invited)

21. Use of directed evolution of mammalian cytochromes P450 for investigating the molecular basis of enzyme function and generating novel biocatalysts. 5rd SWP450 meeting, Camp Allen, Navasota, TX, 2006.

22. Use of directed evolution of mammalian cytochromes P450 for investigating the molecular basis of enzyme function and generating novel biocatalysts. NIEHS Center Seminar Series at UTMB, Galveston, TX; 2005. (Invited)

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23. Engineering cytochrome P450 2B1: rational vs. irrational approach. Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston TX; 2004.

24. Directed evolution approach to engineer mammalian cytochromes P450 for enhanced/altered biological functions. IUBMB/ASBMS 2004, Boston, MA; 2004. (Invited)

25. Allosteric modulation of CYP3A4 by -naphthoflavone and cytochrome b5: evidence by H2O2-supported 7-benzyloxyquinoline oxidation, substrate binding, heme-depletion assays. 3rd

SWP450 meeting, Camp Allen, Navasota, TX; 2004. (Invited)

26. Analysis of H2O2-supported 7-benzyloxyquinoline debenzylation by CYP3A4: effect of the -naphthoflavone and cytochrome b5. Biotransformation Seminar Series, UTMB, Galveston, TX; 2004. (Invited)

27. Mammalian cytochromes P450: rational vs. irrational design, NIEHS Center Seminar Series at UTMB, Galveston, TX; 2003. (Invited)

28. Engineering of cytochrome P450 2B1 for progesterone 21-hydroxylase activity. Drug Metabolism Division Platform Session, EB2004, San Diego, CA; 2003. (Invited)

29. Systematic approach to convert cytochrome P450 regioselectivity across subfamilies, Biotransformation group seminar series, UTMB, Galveston, TX; 2002. (Invited)

30. Engineering of cytochrome P450 2B1 for progesterone 21-hydroxylase activity. 2nd SWP450 meeting, Camp Allen, Navasota, TX; 2002.

31. Cytoplasmic dynein molecular motor: its clutch, gear, accelerator, brake, and cargo. SIUC 6th Annual Molecular and Cellular Biology, Symposium, Southern Illinois University, Carbondale, IL; 2000. (Invited)

BIBLIOGRAPHY

A. THESIS UNDER MY SUPERVISION (UMKC)

Role of cytochrome P450 enzymes on alcohol/nicotine-mediated oxidative stress and cytotoxicity in monocytes/astrocytes: Implications for HIV-infected alcohol/tobacco users

Jin, Mengyao (University of Missouri--Kansas City, 2013-03-13) http://hdl.handle.net/10355/33199

B. ARTICLES/REVIEWS IN PEER-REVIEWED JOURNALS

Citations: 869 (548 since 2009)

h-index: 19 (14 since 2009)

i10-index: 29 (26 since 2009)

UMKC

1. Earla, R., Ande, A., McArthur, C., Kumar, A., Kumar, S. Enhanced nicotine metabolism in HIV-1-infected smokers than uninfected smokers: Simultaneous determination of nicotine and its four metabolites in plasma using a simple and sensitive ESI-LC-MS/MS, Drug Metab. Dispos. 42, 282-293, 2014 (IF - 3.7, Citation - 0).

2. Silverstein, P., Kumar, A., Kumar, S. Alcohol, antiretroviral therapy, HIV-1, HCV, and neurotoxicity. Curr. HIV Res. Accepted (IF - 2.0, Citation - 0)

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3. Shah, A., Kumar, S., Simon, S.D., Singh, D.P., and Kumar, A. HIVgp120 and methamphetamine-mediated oxidative stress increases astrocyte apoptosis via cytochrome P450 2E1. Cell Death and Disease, 4, e850, 2013 (IF - 5.3, Citation - 0)

4. Ande, A., McArthur, C., Kumar A., Kumar, S., Tobacco smoking effect on HIV-1 pathogenesis: Role of cytochrome P450 isozymes. Exp. Opin. Drug Metab. Toxicol. 9,1453-1464, 2013 (IF - 3.1, Citation – 0)

5. Ande, A., McFarlin, K., Kumar, S., Smoking, alcohol consumption, and oxidative stress. Mini-Rev. Org. Chem. Accepted (IF - 2.4, Citation - 0)

6. Kumar, S., Phytoremediation of explosives using transgenic plants, Petroleum and Environment Biotechnology. S4, 001, 2013.(IF - 3.4, Citation - 0)

7. Jin, M., Ande, A., Kumar, A., Kumar, S., Regulation of Cytochrome P450 2E1 Expression by Ethanol: Role of Oxidative Stress-mediated PKC/JNK Pathway. Cell Death Disease (Nature publication), 4, e554 2013 (Corresponding author, S. Kumar) (IF - 5.3, Citation - 1)

8. Shah A., Silverstein, P.A. Kumar, S., Singh, D.P., Kumar, A. Synergistic cooperation between methamphetamine and HIV-1GP120 through the PI3K/AKT pathway induces IL-6 but not IL-8 expression in astrocytes. PLoS ONE, 7, e52060, 2012 (IF - 4.4, Citation - 2)

9. Kumar, S., Challenges and Opportunities of Cytochrome P450-Mediated Phytoremediation. Petrol. Envir., Biotechnol. 4, 1-2, 2012. (IF - 3.1, Citation - 1), Editorial article

10. Kumar, S. Jin, M., Ande, A., Sinha, N., Silverstein, P., Kumar, A., Alcohol consumption effect on antiretroviral therapy and HIV-1 pathogenesis: Role of cytochrome P450 isozymes. Exp. Opin. Drug Metab. Toxicol. 8, 1363-1375, 2012. (IF - 3.1, Citation - 2)

11. Kumar, S., Jin, M., Weemhoff, J., Cytochrome P450-mediated phytoremediation using transgenic plants: A need for engineered cytochrome P450 enzymes. Petrol. Envir., Biotechnol. 3, 1-5, 2012. ( (IF - 3.1, Citation - 5)

12. Jin, M., Kumar, A., Kumar, S., Ethanol mediated induction of cytochrome P450 2A6: Role of oxidative stress-mediated PKC/MEK-Nrf2 pathway. PLoS ONE, 7, e35505, 2012. (IF - 4.4, Citation - 5)

13. Kumar, S. Role of cytochrome P450 in substance abuse mediated HIV-1 pathogenesis and neuroAIDS. J. Drug Metab. Toxicol., 3, 1-4, 2012. (IF - 1.3, Citation - 1), Editorial article

14. 1Ande, A., 1Earla, R., Jin, M., Silverstein, P.S., Mitra, A.K., Kumar, A., Kumar, S., An LC-MS/MS Method for Concurrent Determination of Nicotine Metabolites and the Role of CYP2A6 in Nicotine Metabolite-mediated Oxidative Stress in SVGA Astrocytes. Alcohol and drug dependence, 125, 49-59, 2012. (IF - 4.0, Citation - 4). Highlighted in Global Medical Discovery News, Dec 18, 2012 and Psychology progress, Feb 19, 2013.

15. Silverstein, P.S., Shah, A., Weemhoff, J., Kumar, S., Singh, D.P., Kumar, A., HIV-1 gp120 and Drugs of Abuse: Interactions in the Central Nervous System. Current HIV Research, 10, 369-383, 2012. (IF - 2.0, Citation - 0)

16. Bristow, C.L., Babayeva, M.A., Modarresi, R., McArthur, C.P., Kumar, S., Awasom, C., Ayuk, L., Njinda, A., Achu, P., Winston, R. The α-test: Rapid Cell-free CD4 Enumeration Using Whole Saliva. The Journal of Visualized Experiments, e3999, 2012. (On line Journal, IF - NA, Citation - NA) video: http://www.jove.com/details.php?id=3999&status=a6005k

17. 1Jin, M., 1Earla, R. Shah, A., Rajya L. Earla, Gupte, R., Mitra, A. K., Kumar, A., and Kumar, S., A LC-MS/MS method for concurrent determination of CYP2A6-mediated nicotine metabolites and analysis of nicotine-mediated oxidative stress in U937 macrophages. J. NeuroImmune Pharmacol. 7, 289-299, 2012. (IF - 3.5, Citation - 6)

18. Oezguen, N., Kumar, S., Analysis of cytochrome P450 conserved sequence motifs between helices E and H: Prediction of critical residues for enzyme functions. J. Drug Metab. Toxicol. 2, 110-114, 2011. (IF - 1.3, Citation - 1)

19. Silverstein, P., Shah, A., Gupte, R., Liu, X., Piepho, R., Kumar, S., and Kumar A. Methamphetamine Toxicity and its Implications During HIV-1 Infection. J. Neurorovirology. 17, 401-415, 2011. (IF - 1.2, Citation - 9)

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20. Kumar S. and Kumar, A., Effect of ethanol on spectral binding and inhibition of CYP3A4 with protease inhibitors: An analysis of CYP3A4-potease inhibitors interactions. Alcohol: Clin. Exp. Res. 35, 2121-2127, 2011 (IF - 3.4, Citation - 2)

21. Jin, M., Arya, P. Patel, K., Singh, B., Silverstein, P., Bhat, H., Kumar, A., and Kumar, S., Effect of alcohol on drug efflux protein and drug metabolic enzymes in U937 macrophages. Alcohol Clin. Exp. Res., 35, 1-8, 2011. (IF - 3.4, Citation - 12)

22. Kumar, S., Earla, R., Jin, M., Mitra, A. K., and Kumar, A., Effect of ethanol on spectral binding, inhibition, and activity of CYP3A4 with an antiretroviral drug nelfinavir. Biochem. Biophys. Res. Commun., 402, 163-167, 2010. (IF - 2.7, Citation - 7)

23. Rivera-Amil, V. Kumar, R., Noel Jr., R. J., Garcia, Y., Rodriguez, I. V., Martinez, M., Sariol, C., Kraiselburd, E., Iszard, M., Mukherji, M., Kumar, S., Giavedoni, L. D., and Kumar, A., Lack of Immune Response in Rapid Progressor Morphine-Dependent and SIV/SHIV-infected Rhesus Macaques is Correlated with Down-regulation of TH1 Cytokine. AIDS Research and Human Retroviruses, 26, 919-922, 2010. (IF - 2.1, Citation - 3)

24. Rivera-Amill, V., Silverstein, P. S., Noel, R.J., Kumar, S., and Kumar, A., Morphine and rapid disease progression in non-human primate model of AIDS: Inverse correlation between disease progression and virus evolution. J. NeuroImmune. Pharmacol. 5, 122-132, 2010. (IF - 3.7, Citation - 5)

25. Talakad, J. C., Wilderman, R. P., Davydov, D. R., Kumar, S., and Halpert, J. R., Engineering cytochromes P450 2B6 and 2B11: An insight into the role of residue 334 for stability. Arch. Biophys. Biochem. 494, 152-158, 2010. (IF - 2.9, Citation - 11)

26. Kumar, S., Engineering cytochrome P450 biocatalysts for biotechnology, medicine, and bioremediation. Exp. Opin. Metabol. Toxicol. 6: 1-17, 2010. (IF - 3.5, Citation - 33)

27. Kumar, S., Qiu, H., Oezguen, N., Herlyn, H., Halpert, J. R., and Wojnowski, L., Ligand diversity of human and chimpanzee CYP3A4: Activation of human CYP3A4 by lithocholic acid results from positive selection. Drug Metab. Dispos. 37, 1328-1333, 2009. (IF - 3.7, Citation - 2)

28. Sun, H., Moore, C., Dansette, P. M., Kumar, S., Halpert, J. R., and Yost, G. S. Dehydrogenation of the indoline-containing drug, indapamide, by CYP3A4: Correlation with in silico predictions. Drug Metab. Dispos. 37: 672-684, 2009. (IF - 3.7, Citation - 15)

Note: Among the above publications, eighteen are from my projects, seven are from Dr. A. Kumar’s projects, two are from Dr. Halpert’s project, one is from Dr. Wojnowski’s project, and one is from Dr. McArthur’s project.

Current total citation is approximately 950.

Prior to UMKC

29. Talakad, J. C., Kumar S., Halpert, J. R., Decreased susceptibility of the cytochrome P450 2B6 variant K262R to inhibition by several clinically important drugs. Drug Metab. Dispos. 37, 644-650, 2009. (IF - 3.7, Citation - 18)

30. 1Oezguen, N., 1Kumar, S., Hindupur, A., Braun, W. Muralidhara, B. K., and Halpert, J. R. Identification and analysis of conserved motifs in cytochrome P450 family 2: Functional role of a motif 187RFDYKD192 in P450 2B enzymes. J. Biol. Chem. 283, 21808-21816, 2008. (IF - 5.3, Citation - 10)

31. Pearson, J. T., Wahlstrom, J. L., Dickmann, L. J. Kumar, S., Halpert, J. R. Wienkers, L. C., Foti, R. S., and Rock, D. A. Differential time-dependent inhibition of P450 3A4 and P450 3A5 by raloxifene: A key role for C239 in quenching reactive intermediates. Chem. Res. Toxicol. 20, 1778-786, 2007. (IF - 4.1, Citation - 30)

32. Kumar, S. Zhao, Y., Sun, L., Halpert, J. R, and Muralidhara, B. K., Engineering human

cytochrome P450 2B6 for enhanced expression and stability: Importance of Leu264Phe substitution. Mol. Pharmacol. 46, 11559-11567, 2007. (IF - 4.1, Citation - 17)

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33. Zhao, Y., Sun, L., Muralidhara, B. K., Kumar, S., White, M., Stout, D. C., Halpert, J. R. Structural and thermodynamic consequences of 1-(4-chlorophenyl)imidazole binding to cytochrome P450 2B4. Biochemistry, 281, 5973-5981, 2007. (IF - 3.2, Citation - 36)

34. Kumar, S. Identification of a novel laser dye substrate of mammalian cytochromes P450: Application in rapid kinetic analysis, inhibitor screening, and directed evolution. J. Biomol. Screen. 12, 677-682, 2007. (IF - 2.5, Citation - 3)

35. Sun, L., Chen, C. S., Waxman, D. J., Hong Liu, and Halpert, J. R., and Kumar, S. Re-engineering cytochrome P450 2B11dH for enhanced metabolism of several substrates including the anti-cancer prodrugs cyclophosphamide and ifosfamide. Arch. Biochem. Biophys., 458, 167-174, 2007. (IF - 2.9, Citation - 19)

36. Kumar, S. and Halpert, J. R. Use of directed evolution of mammalian cytochromes P450 for investigating the molecular basis of enzyme function and generating novel biocatalysts. Biochem. Biophys. Res. Commun. 336, 456-464, 2005. (IF - 2.7, Citation - 30)

37. Kumar, S., Sun, L., Muralidhara, B. K., and Halpert, J. R. Engineering mammalian cytochrome P450 2B1 by directed evolution for enhanced catalytic tolerance to temperature and dimethyl sulfoxide. Protein Eng. Des. Selection, 19, 547-554, 2006. This article’s figure was accepted for the cover page caption. (IF - 3.0, Citation - 36)

38. Kumar, S. Liu, H., and Halpert, J. R. Engineering of cytochrome P450 3A4 for enhanced peroxide-mediated substrate oxidation using directed evolution and site-directed mutagenesis. Drug Metab. Dispos. 34, 1958-1965, 2006. (IF - 3.7, Citation - 31)

39. Hernandez, C. E., Kumar, S. Liu, H., and Halpert, J. R. Investigating the role of active site residues of the ligand-bound cytochrome P450 2B4dH/H226Y on ligand binding and substrate metabolism. Arch. Biochem. Biophys. 455, 61-67, 2006. (IF - 2.9, Citation - 15)

40. Kaphalia, L., Kaphalia, B., Kumar, S., Kanz, M. F., and Moslen, M. T. Efficient high performance liquid chromatography/ultraviolet method for determination of diclofenac and 4’hydroxydiclofenac in rat serum. Journal of Chromatography B, 830, 231-237, 2006. (IF - 4.1, Citation - 22)

41. Kumar, S., Davydov, D. R., and Halpert, J. R. Role of cytochrome b5 in modulating peroxide-supported CYP3A4 activity: evidence for a conformational transition and P450 heterogeneity. Drug Metab. Dispos. 33, 1131-1136, 2005. (IF - 3.7, Citation - 29)

42. Kumar, S., Chen, C. S., Waxman, D. J., and Halpert, J. R. Directed evolution of mammalian cytochrome P450 2B1: mutations outside of the active site enhance the metabolism of several substrates including the anticancer prodrugs cyclophosphamide and ifosfamide. J. Biol. Chem. 280, 19569-19575, 2005. (IF - 5.9, Citation - 61) Reprinted in a special issue “Cytochrome P450 Today”, J. Biol. Chem., 2009.

43. Davydov, D. R, Botchkareva. A. E., Kumar, S., He, Y. Q., and Halpert, J. R. An electrostatic driven conformational transition is involved in the mechanism of substrate binding in cytochrome P450eryf. Biochemistry 43, 6475-6485, 2004. (IF - 3.2, Citation - 31)

44. Kumar, S., Scott, E. E., Liu, H., and Halpert, J. R. A rational approach to re-engineer cytochrome P450 2B1 regioselectivity based on the crystal structure of P450 2C5. J. Biol. Chem. 178, 17178-17184, 2003. (IF - 5.9, Citation - 54)

45. Davydov, D. R., Kumar, S., and Halpert, J. R. Allosteric mechanisms in P450eryF with 1- pyrenebutanol: a novel fluorescent probe. Biochem. Biophys. Res. Commun. 294, 806-812, 2002. (IF - 2.7, Citation - 28)

46. Kumar, S., Zhou Y., and Plamann, M. Dynactin-membrane interaction is regulated by the C-

terminal domains of p150Glued. EMBO Reports 2, 939-944, 2001. (IF - 10, Citation - 21)

47. Lee, I. H., Kumar, S., and Plamann, M. Null mutants of the Neurospora crassa Arp1 pointed-end complex show distinct phenotypes. Mol. Biol. Cell. 12, 2195-2206, 2001. (IF - 6.1, Citation - 33)

48. Kumar, S., Lee, I. H., and Plamann, M. Cytoplasmic dynein ATPase is regulated by dynactin-dependent phosphorylation. J. Biol. Chem. 275, 31798-31804, 2000. (IF - 6.7, Citation - 38)

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49. Kumar, S., Lee, I. H., and Plamann, M. Two approaches to isolate dynein ATPase from Neurospora crassa. Biochimie 82, 229-236, 2000. (IF - 3.8, Citation - 3)

50. Kumar, S., Punekar, N. S., Satyanarayan, V., and Venkatesh, K. V. Metabolic fate of glutamate and evaluation of flux through the 4-Aminobutyrate (GABA) shunt in Aspergillus niger. Biotechnol. Bioeng. 67, 575-584, 2000. (IF - 3.7, Citation - 32)

51. Kumar, S., Punekar, N. S. Inhibitor of succinic semialdehyde dehydrogenease by N-formylglycine. J. Enz. Inhib. 13, 369-176, 1998. (IF - 1.6, Citation - 1)

52. Kumar, S. Muscular dystrophy: A genetic disorder. BRIDGE June report, 1998. (IF - NA, Citation - NA)

53. Kumar, S. Enzymes Vs Extremozymes. RESONANCE: J. Sci. Edu. 3, 32-40, 1998. (IF - NA, Citation - 3)

54. Kumar, S., Punekar, N. S. The metabolism of 4-aminobutyrate (GABA) in fungi. Mycol. Res. 101, 403-409, 1997. (IF- 2.9, Citation - 28)

55. Punekar, N. S., Meera G., Sudarshana, S., and Kumar, S. Mechanism of acidogenesis in Aspergillus niger: Status of nitrogen metabolism. In "Microbes for better living", Proc. MICON-94, 9-12, 1994. (IF - NA, Citation - NA) Corresponding author 1Equal contributions Unofficial 2011 Impact Factors were established by dividing the number of articles published in 2010 and 2011 were cited in 2011 based on a search of the Google Scholar Citation Index database, by the number of articles published in the previous two years (2010 and 2011). IF: Impact factor

C. BOOK CHAPTERS

1. Santosh Kumar, Cytochrome P450 Biocatalysts - Current Applications and Future Prospects (2013) In “Industrial Biocatalysis”, Pan Stanford Publishing, Singapore (USA: Boca Raton, FL)

B. ABSTRACTS

UMKC

1. Earla, R., Ande, A., Mitra, A.K., Kumar, A., Kumar, S. Role of CYP2A6 in nicotine metabolism

studied using newly developed LC-MS/MS-SPE method in hiv-1 models monocytes and astrocytes, and plasma from HIV-infected smokers. 19th SNIP Conference, San Juan, PR, April 3-6, 2013.

2. Ande, A., Sinha, N. McArthur, C., Kumar, S. Role of cytochrome P450 (CYP) in smoking and alcohol mediated oxidative stress: implications with HIV-1 pathogenesis. 19th SNIP Conference, San Juan, PR, April 3-6, 2013.

3. Jin, M., Ande, A., Kumar, A., Kumar, S. Regulation of cytochrome P450 2E1 expression by ethanol: role of oxidative stress-mediated PKC/JNK/SP1 pathway. 19th SNIP Conference, San Juan, PR, April 3-6, 2013.

4. Kumar, S., Role of cytochrome P450 enzymes in tobacco/nicotine-mediated effects on HIV-1 model systems. 19th SNIP Conference, San Juan, PR, April 3-6, 2013.

5. Earla, R., Ande, A., Jin, M., Silverstein P.S., Mitra, A.K., Kumar, A., and Kumar, S., Nicotine Metabolism-mediated Oxidative Stress in Astrocytes and Macrophage Studied by using 3200 QTRAP Tandem Mass Spectrometry, American Association of Pharmaceutical Scientists, Chicago, IL, Oct 14-18, 2012.

6. Kumar, S. Central role of cytochromes P450 in tobacco-mediated oxidative stress in maccrophages and astrocytes: implications with HIV-1 pathogenesis and neuroAIDS, 3rd World Congress in Biotechnology, Hyderabad, India, Sep 13-15, 2012.

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7. Ande, A., Sinha, N., McArthur, C., Kumar, S. Central role of cytochromes P450 2A6 in tobacco-mediated oxidative stress in macrophages and astrocytes: implications with hiv-1 pathogenesis and neuroAIDS, 9th ISNV Conference, New York, NY, May 29-June 02, 2012.

8. Kumar, S., Ande, A., Sinha, N., McArthur, C. Central role of cytochromes P450 2A6 in tobacco-mediated oxidative stress in macrophages and astrocytes: implications with hiv-1 pathogenesis and neuroAIDS, 7th Smoking, HIV/AIDS, and Cancer in Health Disparity, Fort Worth, TX, July 11-13, 2012.

9. Ande A., Jin, M., McArthur, C., Kumar A., and Kumar, S., Role of CYP2A6 in nicotine metabolism mediated oxidative stress in monocytes and astrocytes: Implications in HIV-1,18th

SNIP Conference, Honolulu, HI, April 25-28, 2012. 10. Jin, M., Kumar A., and Kumar, S., CYP2E1-mediated alcohol metabolism induces expressions

of CYP2A6 and CYP2E1 through oxidative stress-induced PKC signaling cascades in monocytes and astrocytes, 18th SNIP Conference, Honolulu, HI, April 25-28, 2012.

11. Kumar, S. and Jin, M., Central role of Cytochromes P450 (CYP) in alcohol-mediated oxidative stress and alcohol-antiretroviral therapy (ART) interactions, 18th SNIP Conference, Honolulu, HI, April 25-28, 2012.

12. Kumar, S. and Kumar, A., Tobacco/alcohol, Cytochrome P450, and HIV-1. 44th Annual Conference of Indian Pharmacological Society, Manipal, India, Dec 20-22, 2011.

13. Earla, R., Jin, M., Shah, A., Rajya L. Earla, Gupte, R., Mitra, A. K., Kumar, A., and Kumar, S., A LC-MS/MS method for concurrent determination of CYP2A6-mediated nicotine metabolites and analysis of nicotine-mediated oxidative stress in U937 macrophages, American Society of Mass Spectrometry, Denver, CO, June 5-9, 2011

14. Kumar, S. and Kumar, A., Effect of ethanol on CYP3A4-protease inhibitors physical interactions as determined by spectral binding and enzyme inhibition, 17th SNIP Conference, Clearwater Beach, FL, April 6-10, 2011.

15. Gupte, R., Shah, A., Kumar, S., Kumar, A., Acute ethanol exposure induced upregulation of IL-6and IL-8 in astrocytes is mediated by NFκB pathway, 17th SNIP Conference, Clearwater Beach, FL, April 6-10, 2011.

16. Jin, M., Earla, R., Shah, A., Gupte, R., Mitra, A.K., Kumar, A., Kumar, S., The role of cytochrome P450 on alcohol/nicotine-mediated oxidative stress in U937 macrophages, ; 1School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108-0000. 17th SNIP Conference, Clearwater Beach, FL, April 6-10, 2011.

17. Kumar, S., Jin, M., Silverstein, P., Kumar, A., Effect of alcohol on cytochrome P450 in monocytes/macrophages: Implications in anti-retroviral therapy and oxidative stress, 16th SNIP Conference, Manhattan Beach, CA, April 130-17, 2010.

18. Jin, M., Silverstein, P., Kumar, A., Kumar, S., Cytochrome P450-mediated drug interactions and adverse effects, International Conference on Integrative & Personalized Medicine and 42nd Annual Conference of Indian Pharmacological Society, Kolkata, India, Dec 12-15, 2009.

19. Wojnowski, L., Kumar, S., Qiu, H., Oezguen, N., Herlyn, H., Halpert, J. R., Ligand diversity of human and chimpanzee CYP3A4: Activation of human CYP3A4 by lithocholic acid results from positive selection, Annual Meeting of the German Society of Pharmacology, Mainz, Germany, 2009.

20. Kumar, S., Oezguen, N., Braun, W., and Halpert, J.R. Conserved sequence motifs as an approach to study structure-function relationships of mammalian cytochromes P450, 8th SWP450 meeting, Camp Allen, Navasota, TX; 2009.

Prior to UMKC

21. Talakad, J. C., Sun, L., Kumar, S. and Halpert, J.R. Characterization of the P450 2B6 genetic variant K262R for temperature stability and drug binding, EB/ASPET, San Diego, CA, 2008.

22. Kumar, S., Talakad, J.C., Sun, L., and Halpert, J.R. Engineering of cytochrome P450 2B6 for enhanced expression, stability, and functional studies of the wild-type and genetic variants, EB/ASPET, San Diego, CA, 2008.

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23. Kumar, S., Sun L., Chen, C. S., Waxman, D. J. and Halpert, J. R. Designing mammalian cytochromes P450 for enhanced activity and stability. 6th SW P450 meeting, Camp Allen, Navasota, TX, 2007.

24. Kumar, S., Sun L., Chen, C. S., Waxman, D. J. and Halpert, J. R. Designing mammalian cytochromes P450 for enhanced activity and stability. 15th International Conference on Cytochrome P450, Bled, Slovenia, 2007.

25. Kumar, S., Liu, H., and Halpert, J. R. Use of directed evolution of mammalian cytochromes P450 for investigating the molecular basis of enzyme function and generating novel biocatalysts. 5rd SW P450 meeting, Camp Allen, Navasota, TX, 2006.

26. Kumar, S., Liu, H., and Halpert, J. R. Directed evolution of mammalian cytochromes P450 for investigating the molecular basis of enzyme function and generating novel biocatalysts. ASPET, Experimental Biology, San Francisco, CA, 2006.

27. Kumar, S., Sun, L., Muralidhara, B. K., Liu, H., and Halpert, J. R. Characterization of a laboratory evolved cytochrome P450 2B1 mutant and its further improvement for enhanced tolerance to organic solvents and temperature and enhanced affinity for H2O2. ASBMB, Experimental Biology, San Francisco, CA, 2006.

28. Kumar, S., Chen, C. S., Waxman, D. J., and Halpert, J. R. Directed evolution of cytochrome P450 2B1: mutations outside of the active site enhance the metabolism of several substrates including the anticancer prodrug cyclophosphamide. 14th International conference on cytochrome P450, Dallas, TX, 2005.

29. Kumar, S., Kuriakose, J., He, Y. Q. Malmstrom, R., and Halpert, J. R. A directed evolution approach to engineer mammalian cytochromes P450 for enhanced/altered biological functions. IUBMB/ASBMS, Boston, MA 2004.

30. Kumar, S., He, Y. A., and Halpert, J. R. Analysis of h2o2-supported 7-benzyloxyquinoline

debenzylation by CYP3A4: effect of the -naphthoflavone and cytochrome b5. 3rd SW P450 meeting, Camp Allen, Navasota, TX, 2004.

31. Kumar, S., He, Y. A., and Halpert, J. R. Analysis of H2O2-supported 7-benzyloxyquinoline

debenzylation by CYP3A4: effect of the -naphthoflavone and cytochrome b5. ASPET, Experimental Biology, Washington D.C. 2004.

32. Kumar, S., Kuriakose, J., He, Y. Q. Malmstrom, R., and Halpert, J. R. A directed evolution approach to engineer mammalian cytochromes P450 for enhanced/altered biological functions. ASPET, Experimental Biology, Washington D.C. 2004.

33. Kumar S., and Halpert, J. R. A directed evolution approach to engineer cytochromes P450. 3rd

SW P450 meeting, Camp Allen, Navasota, TX, 2003. 34. Kumar, S., Scott, E. E., Liu, H., and Halpert, J. R. Engineering of cytochrome P450 2B1 for

progesterone 21-hydroxylase activity. ASPET, Experimental Biology, San Diego, CA. 2003. 35. Kumar, S., Scott, E. E., Liu, H., and Halpert, J. R. Engineering of cytochrome P450 2B1 for

progesterone 21-hydroxylase activity. Enzyme Mechanisms Conference, Galveston Island, TX. 6; 2003.

36. Kumar, S., Scott, E. E., and Halpert, J. R. Engineering of cytochrome P450 2B1 for progesterone 21-hydroxylase activity. 2nd Southwest P450 meeting, Camp Allen, Movasota, TX; 2002.

37. Kumar, S., Lee, I. H., and Plamann, M. Regulation of dynein ATPase and dynactin-membrane interaction. Experimental Biology, Orlando, FL, B13: 683.5; 2001.

38. Kumar, S., Lee, I. H., and Plamann, M. Regulation of dynactin-membrane interaction by dynactin pointed-end complex. Gordon research Conference, Andover, NH; 2001.

39. Kumar, S., Zou, Y. and Plamann, M. Dynactin-membrane interaction is regulated by the C-

terminal domains of p150Glued. 40th American Society for Cell Biology, San Francisco, CA;

2000. 40. Kumar, S. Cytoplasmic dynein molecular motor: its clutch, gear, accelerator, brake, and

cargo. SIUC 6th Annual Molecular and Cellular Biology, Symposium, Southern Illinois University, Carbondale, IL; 2000.

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41. Kumar, S., Lee, I. H., and Plamann, M. Biochemical characterization of cytoplasmic dynein from Neurospora crassa. 39th American Society for Cell Biology, Washington, D.C. 249A: 1440; 1999.

42. Kumar, S., Lee, I. H., Minke, P., Tinsley, J. and Plamann, M., Analysis of multiple alleles of Neurospora crassa ro mutants. 20th Fungal Genetics Conference, Pacific Grove, CA. 332; 1998.

43. Kumar, S., and Punekar N. S. 4-Aminobutyrate (GABA) metabolism in normal and acidogenic Aspergillus niger. 66th Annual Meeting of The Society of Biological Chemists, Andhra University, Visakhapatnam, India. 1997.

44. Kumar, S., and Punekar N. S. Biochemical characterization of 4-aminobutyrate transaminases in Aspergilli. National Symposium on Current Trends in Biochemistry and Biotechnology of Fungi, Osmania University, Hyderabad, India. 1996.

45. Kumar, S., and Punekar N. S. Succinic semialdehyde dehydrogenase from Aspergillus niger: A kinetic enquiry. 16th IUBMB, New Delhi, India. 1994.

D. PERSPECTIVE

1. Kumar, S., Newsletter, Society of NeuroImmune Pharmacology (SNIP), April 2012. On the following published article in 2011 by an Early Career Investigator.

Subhas Das, Jennifer Kelschenbach, Richard Charboneau, Roderick A. Barke, and Sabita Roy, Morphine Withdrawal Stress Modulates Lipopolysaccharide induced Interleukin 12 p40 (IL-12p40) Expression by Activating Extracellular Signal-regulated Kinase 1/2, Which Is Further Potentiated by Glucocorticoids. J. Biol. Chem. 286, 29806–29817.

E. CONFERENCES SCENES (HIGHLIGHTS)

1. Kumar, S. Central role of cytochromes P450 2A6 in tobacco-mediated oxidative stress in macrophages and astrocytes: implications with HIV-1 pathogenesis and neuroAIDS. Oral presentation during Symposium on Drugs of Abuse – HIV Infection and NeuroAIDS: A Global Perspective, during 3rd World Congress on Biotechnology, Hyderabad, India during 13-15 Sep, 2012 (Ref: "Latest trends in drugs of abuse – HIV infection and neuroAIDS". Future Virology. 2013. 8(2): 121–127; DOI 10.2217/fvl.12.134).

F. NEWS

1. Ande, A., Earla, R., Jin, M., Silverstein, P.S., Mitra, A.K., Kumar, A., Kumar, S., An LC-MS/MS Method for Concurrent Determination of Nicotine Metabolites and the Role of CYP2A6 in Nicotine Metabolite-mediated Oxidative Stress in SVGA Astrocytes, Alcohol and drug dependence, Global Medical Discovery News, Dec 18, 2012 (http://globalmedicaldiscovery.com/?s=ande%2C+earla).

2. Ande, A., Earla, R., Jin, M., Silverstein, P.S., Mitra, A.K., Kumar, A., Kumar, S., An LC-MS/MS Method for Concurrent Determination of Nicotine Metabolites and the Role of CYP2A6 in Nicotine Metabolite-mediated Oxidative Stress in SVGA Astrocytes, Alcohol and drug dependence, Psychology Progress, Feb 19, 2013. (http://psychologyprogress.com/an-lc-msms-method-for-concurrent-determination-of-nicotine-metabolites-and-the-role-of-cyp2a6-in-nicotine-metabolite-mediated-oxidative-stress-in-svga-astrocytes/)

G. FACULTY 1000 RECOMMENDATIONS

A total of eight articles have been recommended. For detail please see (http://f1000.com/prime/my/evaluations/approved)

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H. MANUSCRIPT IN REVIEW

1. Nookala, A.R. Ande, A., Li, J., Wang, L. Li, W. Kumar, S. Kumar, A. Effect of methamphetamine on spectral binding and ligand docking of anti-HIV drugs with CYP3A4. Drug Metab. Dispos. (IF - 3.7), In revision

2. Earla, R., Kumar, S., Wang, L., Bosinger, S., Li, J., Shah, A., Ganagwani, M.K., Nookala, A.R., Liu, X., Cao, L., Jackson, A., Fox, H., Li, W., Kumar, A. Enhanced methamphetamine metabolism in rhesus macaque as to human by cytochrome P450 pathways: An analysis using a novel LCMS/MS method and docking study. Drug Metab. Dispos. (IF - 3.7), In revision

3. Ande, A., McArthur, C., Ayuk, L., Awasom, C., Achu, P.N., Njinda, A., Nookala, A., Simon, S., Kumar, A., Kumar, S. Effect of mild-to-moderate drinking and smoking on viral load, cytokines, and oxidative stress in HIV-1-infected individuals. Curr. HIV Res. (IF - 2.0)

4. Ande, A., McArthur, C., Sinha N., Kumar, A., Kumar, S. Effect of drinking and smoking on oxidative stress and expression of cytochrome P450 and antioxidant enzymes in HIV-1-infected individuals in monocytes. J Neuroimmune Pharmacol. (IF - 3.8)

5. *Kumar, S., *Rao, P.S.S., Kumar, A. Impact of substance of abuse on antiretroviral therapy in HIV-infected populations: Adherence, antiretroviral response, and toxicity. Exp Rev. Clin Pharmacol. (IF -) *Equal contribution.

6. Rao, P.S.S., Cory, J.T., Kumar, S. New antiretroviral therapies and potential drug interactions in HIV-infected drug abusers. J Antivir Antiretrovir. (IF* - 3.0)

7.

I. MANUSCRIPT UNDER PREPARATION