My research examines molecular determinants of smoking cessation combining formal skill sets in medicine, public health, pharmacogenetics/pharmacogenomics, and functional neuroimaging. I have conducted pharmacogenetics studies of nicotine replacement therapy and bupropion for smoking cessation, finding significant gene x treatment interactions for bupropion and identifying mediating pathways for bupropion smoking cessation efficacy. The overall goal is to translate this research to practice.

Biography

Dr. David is Director of Research in Family Medicine. His research spans the translational continuum from molecular genetics to health policy and is focused on smoking cessation. Recently published studies have identified genetic (pharmacogenetic and pharmacogenomic) influences on drug response to bupropion and nicotine replacement therapy for smoking cessation and have examined brain reward pathways using functional neuroimaging. He is actively translating these data into practice and policy through cost-effectiveness analyses, meta-analyses, and medical informatics working with a Trans-Atlantic transdisciplinary research team. He is also active in clinical practice and education.
Dr. David trained at the University of Washington, the Harvard School of Public Health, the University of Oxford where he was mentored by Sir Richard Doll, was Chief Resident at Dartmouth-Hitchcock Medical Center, and a Robert Wood Johnson Foundation Generalist Physician Faculty Scholar. He has worked as a collaborator and protégé of former Surgeon General C. Everett Koop on numerous projects translating nicotine dependence research into tobacco control policy. He is also Director of the Primary Care Genetics Laboratory & Translational Research Center and C. Everett Koop Health Policy Fellowship.

Institutions

Mhri

Research Description

My research examines molecular determinants of smoking cessation combining formal skill sets in medicine, public health, pharmacogenetics/pharmacogenomics, and functional neuroimaging. My educational background incorporates the following degrees and achievements:

Qualifications:
• Zoology (B.S.), University of Washington College of Arts and Sciences, 1990
• Medicine (M.D.), University of Washington School of Medicine, 1995
• Family Medicine, Residency (Chief Resident), Dartmouth-Hitchcock Medical Center, Dartmouth Medical School, 1998
• Board Certification in Family Medicine (American Board of Family Medicine Diplomate), 1998, renewed 2005.
• Public Health (S.M. Health and Social Behavior), Harvard School of Public Health, 1999
• Genetics, (Visiting Fellowship, Pharmacogenetics), University of Oxford Cancer Research UK General Practice Research Group, 2002
• Pharmacology, (D.Phil. utilizing functional magnetic resonance imaging (fMRI) of the brain and positron emission tomography (PET)), University of Oxford, 2006

Appointments:
• Director, C. Everett Koop Health Policy Fellowship
• Director of Research and Assistant Professor of Family Medicine
• Director, Primary Care Genetics Laboratory and Translational Research Center
• Former President, Green College Middle Common Room, Oxon

In my position as Research Director in Family Medicine at Brown Medical School, I have conducted pharmacogenetics studies of nicotine replacement therapy and bupropion for smoking cessation, finding significant gene x treatment interactions for bupropion and identifying mediating pathways for bupropion smoking cessation efficacy [1, 2]. In collaboration with the Oxford Centre for Functional Magnetic Resonance Imaging (fMRI) of the Brain, I developed an fMRI protocol to examine tobacco cue reactivity demonstrating activation of the mesoaccumbens system (ventral striatum/nucleus accumbens, anterior cingulate gyrus, orbitofrontal cortex) to smoking-related picture cues in addicted smokers and greater activation in these regions in smokers compared to non-smokers [3]. Working with Professors Edith Sim (Pharmacology) and Paul Matthews (Clinical Neuroscience), using Positron Emission Tomography (PET), we demonstrated that a candidate gene polymorphism for nicotine dependence in the serotonin transporter gene had a global and statistically significant effect on binding potential to the serotonin 5-HT1A receptor [4], potentially explaining the pharmacogenetic mechanisms underlying differential treatment response to selective serotonin reuptake inhibitors and to the brain's response to environmental stimuli related to smoking [5].

All of these studies have been part of an integrated approach to translational smoking cessation research spearheaded in the Primary Care Genetics Laboratory and Translational Research Center, which I direct at Brown Medical School. The overarching goal has been to generate knowledge and translate research into evidence-based practice and health policy through the C. Everett Koop Health Policy Fellowship—See Primary Care Genetics Laboratory at http://bms.brown.edu/pcgl/ [6-12]. My hope is that through application of research from molecular to societal levels will offer innovative solutions to pressing public health needs, particularly in cancer and cardiovascular disease prevention, drug development and discovery, and public health.

References:

1. David, S., Niaura, R., Papandonatos, G., Shadel, W., Burkholder, G., Britt, D., Day, A., Stumpff, J., Hutchison, K., Murphy, M., Johnstone, E., Griffiths, S. E., Walton, R., "Does the DRD2-Taq1 A polymorphism influence treatment response to bupropion hydrochloride for reduction of the nicotine withdrawal syndrome?" Nicotine Tob Res, 2003. 5(6): p. 935-42.


2. David, S.P., Brown, R.A., Papandonatos, G.D., Lloyd-Richardson, E.E., Munafo', M.R., Shields, P.G., Lerman, C., Strong, D., McCaffery, J., Niaura, R., "Pharmacogenetic clinical trial of sustained-release bupropion for smoking cessation". Nicotine Tob Res, 2005 (manuscript under review).


3. David, S.P., Munafo, M. R., Johansen-Berg, H., Smith, S. M., Rogers, R. D., Matthews, P. M., Walton, R. T., "Ventral striatum/nucleus accumbens activation to smoking-related pictorial cues in smokers and nonsmokers: a functional magnetic resonance imaging study". Biol Psychiatry, 2005. 58(6): p. 488-94.


4. David, S.P., Murthy, N. V., Rabiner, E. A., Munafo, M. R., Johnstone, E. C., Jacob, R., Walton, R. T., Grasby, P. M., "A functional genetic variation of the serotonin (5-HT) transporter affects 5-HT1A receptor binding in humans". J Neurosci, 2005. 25(10): p. 2586-90.


5. David, S.P. "Effects of the Serotonin Transporter 5-HTTLPR polymorphism on nucleus accumbens activation to smoking-related pictorial cues in smokers: An fMRI Study". In British Psychological Society's Quinquennial Meeting. 2005. Manchester, United Kingdom: British Psychological Society.


6. David, S.P., "Pharmacogenetics". Prim Care, 2004. 31(3): p. 543-559.


7. David, S.P. "A Civic and Scientific Role for Family Doctors in the Promotion of Global Tobacco Control (Plenary Speaker)". In Proceedings from the 7th World Conference of Family Doctors/American Academy of Family Physicians Scientific Assembly. 2004. Orlando, FL, USA: WONCA.


8. David, S.P., Eaton, C. B., Taylor, J. S., Stamp, M. J., Cyr, M., Siegel, B., Gramling, R., Walton, R., "Envisaging and applying a unifying three-dimensional theoretical framework for generalist physicians". Med Health R I, 2004. 87(11): p. 336-40.


9. David, S., W. DeJong, and N. Resnick, "International tobacco control: a focus group study of U.S. anti-tobacco activists". J Public Health Policy, 2001. 22(4): p. 415-28.


10. David, S.P., "The Transatlantic Conference on Tobacco (TACT): a model for international tobacco policy activism". J Cancer Educ, 1998. 13(4): p. 253-4.


11. David, S.P. and D.S. Greer, "Social marketing: application to medical education". Ann Intern Med, 2001. 134(2): p. 125-7.


12. David, S.P., "Media advocacy for the office-based teacher of family medicine". Fam Med, 2001. 33(1): p. 16-8.

Awards

Glaxo-Wellcome Family Practice Scholar Award
American Academy of Family Physicians, June 1997

Advanced Research Training Award
American Academy of Family Physicians,
December 2001 (see also 'GRANTS')

Dean's Teaching Excellence Award
Brown Medical School, May 2001

Robert Wood Johnson Foundation
Generalist Physician Faculty Scholars Award, July 2002 (see also 'GRANTS')

Profiles in Competence Award, Lifelong Learning
Brown Medical School, May 2002

National Institute on Drug Abuse
KO8 Mentored Clinical Scientist Development Award, September 2002 (see also 'GRANTS')

Elected to Board of Rhode Island Public Health Association, May 2003

Affiliations

American Academy of Family Physicians
July 1995 to present

Society of Teachers of Family Medicine
April 2000 to present

World Organization of Family Doctors (WONCA)
July 2000 to present

Society for Research on Nicotine and Tobacco (SRNT)
August 2000 to present

Royal College of General Practitioners
Virtual Genetics Group
December 2001 to present

American Association for Cancer Research (AACR)
September 2003 to present

Organization for Human Brain Mapping (HBM)
January 2004 to present

Funded Research

1. Grant #111869: Advanced Research Training Award. American Academy of Family Physicians.
   Funding Period: 12/2001 to 11/2003, Amount: $99,699.00
   Principal Investigator


2. Grant #106863: "¡Ya No Fumo!: An Innovative Smoking Cessation Intervention for Latino/Hispanic Patients in Pawtucket and Central Falls, Rhode Island".
   Rhode Island Department of Health
   Funding Period: 2/01/2002 to 6/30/2003, Amount: $59,965.00; $42,500/year since 07/01/2003.
   Principal Investigator


3. National Cancer Institute (NCI) Travel Award.
   Funding Period: 2/20/2002 to 2/23/2002, Amount: $1,000.00
   Principal Investigator


4. Cancer Research UK Laboratory Consumables Grant.
   Cancer Research UK
   Funding Period: 2/01/02 to 1/31/04, Amount: £20,000.00
   Co-Investigator


5. Grant # 045453: "Enhancing the State of the Art of Smoking Cessation through Pharmacogenetics". Robert Wood Johnson Generalist Physician Faculty Scholars Award
   The Robert Wood Johnson Foundation
   Funding Period: 7/01/2002 to 6/30/2006,
   Amount: $295,640.00
   Principal Investigator


6. Grant #1 K08 DA14276-02: "Psychobiological and Genetic Determinants of Smoking Cessation".
   NIDA K08 Mentored Clinical Scientist Award.
   National Institute on Drug Abuse
   Funding Period: 9/27/2002 to 8/31/2007,
   Direct Amount: $772,711
   Principal Investigator


7. National Cancer Institute (NCI) Travel Award.
   National Cancer Institute
   Funding Period: 2/19/2002 to 2/22/2002, Amount: $1,000.00
   Principal Investigator


8. Grant #1 R13 CA101634-01: Primary Care Genetics Cancer Prevention Conference.
   National Cancer Institute and National Human Genome Research Institute R13 Conference Grant.
   Funding Period: 4/01/2003 (one time)
   Direct Amount: $10,000
   Principal Investigator


9. P01 Transdisciplinary Tobacco Use Research Center. "Nicotine Dependence through Generations".
   National Cancer Institute/National Institute on Drug Abuse/National Institute on Alcohol and Alcoholism
   Competitive Renewal Grant
   Funding period: 10/2005 to 09/2010,
   Amount: $100,000
   Co-Investigator

Teaching Experience

1. BIOMED 580: Family Medicine Clerkship
(Approximately 70 students/year)
I was Family Medicine Core Clerkship Director (Interim), 2000-2001
A. Developed curriculum, evaluated, and taught:
B. "Smoking Cessation"
January 2000 to March 2003
C. "Ability VII-Social and Community Contexts of Care" March 2000 to March 2003
D. "Health Promotion and Disease Prevention in Non-Heterosexual Patients"
E. "Reducing Health Disparities in Cancer"
January, 2002 to March, 2003

2. "Genetics in Primary Care: A Brown Oxford Transatlantic Videoconference"
Planned, hosted, and presented in NCI/NHGRI-funded teleconference with the University of Oxford.
George Auditorium, Rhode Island Hospital
April 10, 2003

3. US Cochrane Center Peer Review Workshop
Instructor
Brown University
October 4, 2003

4. Brown Family Medicine Residency
Curriculum development and teaching genetics
September 2003 to present

Courses Taught

• Family Medicine Core Clerkship (580)

View My Full Publication List in pdf format

Selected Publications

• Uhl GR, Liu QR, Drgon T, Johnson C, Walther D, Rose J, David SP, Niaura R, Lerman C. Molecular genetics of successful smoking cessation: convergent genome-wide association results. Arch Gen Psychiatry (manuscript in press).(IN PRESS)
• Paul R, Grieve S, Niaura R, David SP, Laidlaw D, Cohen R, Sweet L, Taylor G, Clark R, Pogun S, Gordon E. Impact of cigarette smoking on the microstructural integrity of white matter in healthy adults: a diffusion tensor imaging study. Nicotine Tob Res. (manuscript in press).(IN PRESS)
• Welton NJ, Johnstone EC, David SP, Munafò MR. A Cost-Effectiveness Analysis of Genetic Testing to Aid Treatment Choice for Smoking Cessation. Nicotine Tob Res. (manuscript in press).(IN PRESS)
• David SP, Munafo' M, Johansen-Berg, H, MacKillop J, Sweet L, Cohen RA, Rogers RD, Matthews PM, Walton RT. Effects of acute nicotine abstinence on cue-elicited ventral striatum/nucleus accumbens activation in female cigarette smokers: A functional magnetic resonance imaging study. Brain Imaging & Behavior. 2007 May (epub ahead of press).(2007)
• Johnstone EC, Elliot KM, David SP, Murphy MFG, Walton RT, Munafò MR. Association of Association of COMT Val108/158Met Genotype with Smoking Cessation in a Nicotine Replacement Therapy Randomized Trial. Cancer Epidemiol Biomarkers Prev. 2007 Jun;16(6):1065-9.(2007)
• David SP, Brown RA, Papandonatos GD, Lloyd-Richardson EE, Munafo' MR, Shields PG, Lerman C, Strong D, McCaffery J, Niaura R. Pharmacogenetic clinical trial of sustained-release bupropion for smoking cessation. Nicotine Tob Res. 2007 Aug;9(8):821-33.(2007)
• David SP, Munafò MR, Murphy MFG, Walton RT, Johnstone EJ. The serotonin transporter (5-HTTLPR) polymorphism and treatment response to nicotine patch in primary care: Follow-up of a randomized controlled trial. Nicotine Tob Res. 2007 Feb;9(2):225-31.(2007)
• David SP, Munafò MR, Murphy MFG, Proctor M, Walton RT, Johnstone EC. Genetic variation in the dopamine D4 Receptor (DRD4) gene and smoking cessation: Follow up of a randomised clinical trial of transdermal nicotine patch. Pharmacogenomics J. 2007 Mar 27; [Epub ahead of print](2007)
• David SP, Strong D, Brown RA, Lloyd-Richardson EE, Wileyto P, Evins AE, Shields PG, Lerman C, Niaura R. Bupropion efficacy for smoking cessation is influenced by the DRD2-Taq1A polymorphism: Analysis of pooled data from two clinical trials. Nicotine Tob Res. 2007;9(12):1251-1257.(2007)
• Koplan KE, David SP, Rigotti NA. 10-minute consultation: Smoking cessation. BMJ. 2007 (manuscript in press).(2007)
• David S, Evins AE, Lancaster T, Stead LF. Opioid antagonists for smoking cessation. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD003086.(2006)
• David SP, Munafo' M, Johansen-Berg, H, Smith SM, Rogers RD, Matthews PM, Walton RT. Ventral Striatum/Nucleus Accumbens Activation to Smoking-Related Pictorial Cues in Smokers and Non-Smokers: An fMRI study. Biol Psychiatry. 2005 Sep 15;58(6):488-94.(2005)
• David SP, Murthy NV, Rabiner EA, Munafo MR, Johnstone EC, Jacob R, Walton RT, Grasby PM. A functional genetic variation of the serotonin (5-HT) transporter affects 5-HT1A receptor binding in humans. J Neurosci. 2005 Mar 9;25(10):2586-90.(2005)
• Munafò M, Bradburn M, Bowes L, David SP. Are there sex differences in transdermal nicotine replacement therapy efficacy? A meta-analysis. Nicotine Tob Res. 2004 Oct;6(5):769-76.(2004)
• David SP, Taylor JS, Monroe A, Goldman R, Green AR, Boss JD, Sagaties D. Evaluation of an educational intervention for medical students to promote competency in social and community determinants of health. Annals of Behavioral Science & Medical Education 2004;10(2):268-273.(2004)
• David SP, Niaura RS, Papandonatos GD, Shadel WG, Britt DM, Day A, Stumpff J. Does the DRD2-Taq1 A polymorphism influence treatment response to bupropion hydrochloride for reduction of the nicotine withdrawal syndrome? Nicotine Tob Res. 2003 Nov;5(6):935-42.(2003)
• David SP, Johnstone E, Griffiths SE, Murphy M, Yudkin P, Mant D, Walton R. No association between functional catechol O-methyl transferase 1947A>G polymorphism and smoking initiation, persistent smoking or smoking cessation. Pharmacogenetics. 2002 Apr;12(3):265-8.(2002)
• David S, DeJong W, Resnick N. International tobacco control: a focus group study of U.S. anti-tobacco activists. J Public Health Policy. 2001;22(4):415-28.(2001)
• David S, Lancaster T, Stead LF. Opioid antagonists for smoking cessation. Cochrane Database Syst Rev. 2001;(3):CD003086.(2001)
• David SP, Greer DS. Social marketing: application to medical education. Ann Intern Med. 2001 Jan 16;134(2):125-7.(2001)