PHA/Pfizer Proof of Concept Research Grant Winner 2011

Ferhaan Ahmad, MD, PhDFerhaan Ahmad, MD, PhD

Departments of Medicine and Human Genetics
University of Pittsburgh, Pittsburgh
Title: "Applying Genomics as a Springboard to Novel Mechanisms of Pulmonary Hypertension"
Term: October 1, 2011 and will end September 30, 2012


 

 





Summary of Research Project:

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by abnormal thickening of blood vessel walls. Even with the best treatments, only about half of patients survive five years after diagnosis. This project will analyze the molecular and cellular pathways that different lung blood vessel cells follow to become abnormal in PAH, and identify new treatments that reverse these pathways and possibly cure patients. To accomplish this goal, we plan to study blood vessels from lungs removed from patients with PAH at the time they are undergoing lung or heart-lung transplant operations.

Curriculum Vitae

NAME: Ferhaan Ahmad, MD, PhD
POSITION TITLE: Assistant Professor of Medicine and Human Genetics; Director, Cardiovascular Genetics Center

EDUCATION/TRAINING

INSTITUTION AND LOCATION DEGREE YEAR(S) FIELD OF STUDY
Marianopolis College, Montreal, Quebec D.C.S. 1984-1986 Health Sciences
McGill University, Montreal, Quebec M.D.,C.M. 1986-1991 Pre-Medicine/Medicine
McGill University, Montreal, Quebec Resident 1991-1994 Internal Medicine
McGill University, Montreal, Quebec Fellow 1994-1996 Cardiology
Baylor College of Medicine, Houston Ph.D. 1997-2001 Genetics
Brigham and Women’s Hospital, Boston Fellow (part-time) 2002-2003 Nuclear Cardiology
Harvard Medical School
Howard Hughes Medical Institute, Boston
Associate 2001-2005 Genetics


Positions and Honors

Positions and Employment

  • 2/1/2005 - present Assistant Professor, Cardiovascular Institute, Departments of Medicine (primary) and Human Genetics (secondary), University of Pittsburgh, Pittsburgh.
  • 9/1/2005 - present Director, Cardiovascular Genetics Center, University of Pittsburgh, Pittsburgh.
  • 7/1/2008 - present Associate Director for Research, UPMC Cardiology Fellowship Training Program.
  • 4/1/2010 - present Director, Hypertrophic Cardiomyopathy Center, UPMC.
  • 5/1/2011 - present Member, Vascular Medicine Institute, University of Pittsburgh, Pittsburgh.
  • 1986 Governor General's Medal for Highest Academic Distinction among Graduating Science Students, Marianopolis College.

Honors and Awards

  • 1987 Faculty Scholar, a recognition given annually to the top-ranked students in the Faculty of Science, McGill University.
  • 1988 Canadian Society for Clinical Investigation Student Award for outstanding original research.
  • 1991 Nomination for the Alexander D. Stewart Prize, awarded to the member of the graduating class in the McGill University Faculty of Medicine who, in the opinion of the faculty and fellow students, presents in every respect the highest qualifications to practice the profession.
  • 1996 Canadian Institutes of Health Research Clinician Scientist Award, Phase I (6 Years).
  • 1999 Finalist, Young Investigator Awards Competition, American College of Cardiology.
  • 1999 University of Texas Award for Excellence in Research, National Research Forum.
  • 2006 Doris Duke Charitable Foundation Clinical Scientist Development Award.
  • 2006 Visiting Professor, All India Institute of Medical Sciences, New Delhi, India.
  • 2007 Invited Plenary Session Speaker, Keystone Symposium on Molecular Pathways in Cardiac Development and Disease, Breckenridge, Colorado.
  • 2011 Invited Speaker, International Heart Forum, Beijing, PR China.
  • 1991 Licensing Examination of the Federation of State Medical Boards of the US.

Other Experience and Professional Memberships

  • 1995 - present Fellow, The Royal College of Physicians and Surgeons of Canada (FRCPC).
  • 1997 - present Member, American Heart Association, Council on Basic Cardiovascular Sciences.
  • 1999 - present Diplomate in Cardiovascular Disease, American Board of Internal Medicine.
  • 2003 - present Diplomate, Certification Board of Nuclear Cardiology.
  • 2004 - present License Number MD425468, Pennsylvania State Board of Medicine.
  • 2005 - present Reviewer, American Journal of Respiratory and Critical Care Medicine, Biochimica et Biophysica Acta (BBA), BMC Medical Genetics, BMC Physiology, Circulation, CirculationResearch, Circulation: Cardiovascular Genetics, Circulation: Heart Failure, Clinical Genetics, Journal of Molecular and Cellular Cardiology, Journal of the American College of Cardiology, PLoS Medicine, PLoS ONE.
  • 2006 - present Grant Reviewer; Barth Syndrome Foundation; Canada Foundation for Innovation; Canadian Institutes of Health Research; American Heart Association; Heart Research UK; The Wellcome Trust.
  • 2007 - present Member / Chair, Fellows Research Day Task Force, American Heart Association
  • 2009 - present Member, American Physiological Society, Cardiovascular Section.

Selected peer-reviewed publications 

  1. Ahmad F, Li D, Karibe A, Gonzalez O, Tapscott T, Hill R, Weilbaecher D, Blackie P, Furey M, Gardner M, Bachinski LL, Roberts R. Localization of a gene responsible for arrhythmogenic right ventricular dysplasia (ARVD) to chromosome 3p23. Circulation 1998;98:2791-2795.
  2. Ahmad F, Gonzalez O, Ramagli L, Xu J, Siciliano MJ, Bachinski LL, Roberts R. Identification and characterization of a novel gene (c4orf5) located on human chromosome 4q with specific expression in cardiac and skeletal muscle. Genomics 2000;70:347-353.
  3. Ahmad F, Arad M, Musi N, He H, Wolf C, Branco D, Perez-Atayde AR, Stapleton D, Bali D, Xing Y, Tian R, Goodyear LJ, Berul CI, Ingwall JS, Seidman CE, Seidman JG. Increased á2 subunit-associated AMPK activity and PRKAG2 cardiomyopathy. Circulation 2005;112:3140-3148.
  4. Banerjee SK, Ramani R, Saba S, Rager J, Tian R, Mathier MA, Ahmad F*. A PRKAG2 mutation causes biphasic changes in myocardial AMPK activity and does not protect against ischemia. Biochem Biophys Res Commun 2007;360:381-387. (doi:10.1016/j.bbrc.2007.06.067)
  5. Ahmad F*, Banerjee SK, Lage ML, Huang XN, Smith SH, Saba S, Rager J, Conner DA, Janczewski AM, Tobita K, Tinney JP, Moskowitz IP, Perez-Atayde AR, Keller BB, Mathier MA, Shroff SG, Seidman CE, Seidman JG. The role of cardiac troponin T quantity and function in cardiac development and dilated cardiomyopathy. PLoS ONE 2008;3:e2642.
  6. Banerjee SK, McGaffin KR, Pastor-Soler NM, Ahmad F*. SGLT1 is a novel cardiac glucose transporter that is perturbed in disease states. Cardiovasc Res 2009;84:111-118.
  7. Banerjee SK, McGaffin KR, Huang XN, Ahmad F*. Activation of cardiac hypertrophic signaling pathways in a transgenic mouse with the human PRKAG2 Thr400Asn mutation. Biochim Biophys Acta 2010;1802:284-291. (doi:10.1016/j.bbadis.2009.12.001)
  8. Rajkumar R, Konishi K, Richards T, Wiechert A, Ishizawar D, Kaminski N, Ahmad F*. Genome-wide RNA expression profiling in lung identifies distinct signatures in idiopathic pulmonary arterial hypertension and secondary pulmonary hypertension. Am J Physiol Heart Circ Physiol 2010;298:H1235-1248.
  9. Banerjee SK, Wang DW, Alzamora R, Huang XN, Pastor-Soler NM, Hallows KR, McGaffin KR, Ahmad F*. SGLT1, a novel cardiac glucose transporter, mediates increased glucose uptake in PRKAG2 cardiomyopathy. J Mol Cell Cardiol 2010;49:683-692.
  10. Li D, Ahmad F, Gardner MJ, Weilbaecher D, Hill R, Karibe A, Gonzalez O, Tapscott T, Sharratt GP, Bachinski LL, Roberts R. The locus of a novel gene responsible for arrhythmogenic right ventricular dysplasia characterized by early onset and high penetrance maps to chromosome 10p12-p14. Am J Hum Genet 2000;66:148-156. PMCID: PMC1288320
  11. Schmitt JP, Kamisago M, Asahi M, Li GH, Ahmad F, Mende U, Kranias EG, MacLennan DH, Seidman JG, Seidman CE. Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban. Science 2003;299: 1410-1413.
  12. Schmitt JP, Debold EP, Ahmad F, Armstrong A, Frederico A, Conner D, Mende U, Lohse MJ, Warshaw D, Seidman CE, Seidman JG. Cardiac myosin missense mutations cause dilated cardiomyopathy in mouse models and depress molecular motor function. Proc Natl Acad Sci 2006;103:14525-14530. PMCID: PMC1599993
  13. Wolf, CM, Arad M, Ahmad F, Sanbe A, Bernstein SA, Toka O, Konno T, Morley G, Robbins J, Seidman JG, Seidman CE, Berul CI. Reversibility of PRKAG2 glycogen-storage cardiomyopathy and electrophysiological manifestations. Circulation 2008;117:144-154.
  14. Wolf CM, Wang L, Alcalai R, Pizard A, Burgon PG, Ahmad F, Sherwood M, Branco DM, Wakimoto H, Fishman GI, See V, Stewart CL, Conner DA, Berul CI, Seidman CE, Seidman JG. Lamin A/C haploinsufficiency causes dilated cardiomyopathy and apoptosis-triggered cardiac conduction system disease. J Mol Cell Cardiol 2008;44:293-303. (doi:10.1016/j.yjmcc.2007.11.008)
  15. Schmitt JP, Ahmad F, Lorenz K, Hein L, Asahi M, MacLennan DH, Seidman CE, Seidman JG, Lohse MJ. Alterations of phospholamban function can exhibit cardiotoxic effects independent of excessive SERCA2a inhibition. Circulation 2009;119:436-444.

Research Support

Ongoing Research Support

  1. M2010-0055
    09/01/2010 – 08/30/2013
    Pittsburgh Foundation Program for Medical Research
    A Pittsburgh Collaborative Network to Combat Right Heart Failure in Pulmonary Hypertension
    The overall goal of this proposal is to identify these molecular pathways and prospectively to validate their prognostic and therapeutic utility by (1) in silico analysis of genome-wide expression data of mRNA and miRNA in lung tissue, RV tissue, and blood; and (2) in vivo longitudinal correlation of changes in expression with RV function in PAH subjects.
    Role: Ferhaan Ahmad, Principal Investigator
  2. VMI / CTSI Pilot Project Program in Hemostasis and Vascular Biology (P3HVB) (Ahmad)
    03/01/2011 – 02/29/2012
    Vascular Medicine Institute (VMI), University of Pittsburgh
    The Role of Platelet Gene Expression in the Pathogenesis of Pulmonary Arterial Hypertension
    The major goal of this project is to establish platelet mRNA and miRNA expression signatures that are associated with PAH subjects relative to normal control subjects, and signatures that predict the onset, course, and drug responsiveness of PAH.
    Role: Ferhaan Ahmad, Principal Investigator
  3. GPCL Pilot Program Grant
    07/1/2010 – 06/30/2011
    University of Pittsburgh
    Transcriptional Mechanisms of Right Heart Failure in a Rat Model of Pulmonary Arterial Hypertension
    The major goal of this project is to establish a longitudinal transcriptome signature in RV tissue as RV failure develops in a rat model of pulmonary arterial hypertension (PAH).
    Role: Ferhaan Ahmad, Principal Investigator
  4. Research Developmental Grant (Ahmad)
    09/01/2010 – 08/31/2011
    American Respiratory Alliance
    Identification of Master Transcriptional Regulators to Cure Pulmonary Hypertension
    The major goal of this project is to identify master transcriptional regulators which lead to characteristic changes in pulmonary mRNA expression in pulmonary hypertension.
    Role: Ferhaan Ahmad, Principal Investigator
  5. R01 HL095397 (Kaminski)
    09/30/2008 – 09/29/2012
    National Institutes of Health
    Molecular Phenotypes Across and Within Disease Boundaries in IPF and COPD
    In this proposal we plan to use the lung Tissue Resource Consortium (LTRC), a large NIH sponsored collection of well characterized lung samples from patients with IPF and COPD to define known disease phenotypes and discover new disease phenotypes using gene expression microarrays, a novel platforms for high throughput parallel PCR (SmartChip) as well as novel computational approaches.
    Role: Ferhaan Ahmad, Co-Investigator

Pending Research Support

  1. 1 R21 HL109812
    07/01/2011 – 06/30/2013
    National Institutes of Health
    Dissecting Genetic Mechanisms of Hypertrophic Cardiomyopathy by ENU Mutagenesis
    PRINCIPAL INVESTIGATOR: AHMAD, Ferhaan
    ATS Grant Application Form – 2007 - 1 1 -
    The overall goal of this proposal is to leverage the unique resource available to us through an ongoing ENU mutagenesis program to recover novel genes associated with HCM.
    Role: Ferhaan Ahmad, Principal Investigator
  2. 1 R03 HL110786-01
    09/30/2011 – 09/29/2013
    NIH/NHLBI
    Applying Genomics as a Springboard to Novel Mechanisms of Pulmonary Hypertension
    The overall goal of this proposal is to determine the role of candidate biological networks in distinct pulmonary vascular cell types obtained from subjects with IPAH and APAH, and to determine how these networks lead to the integrated phenotype of dysfunction in pulmonary vessels of different calibers.
    Role: Ferhaan Ahmad, Principal Investigator
    Overlap
    There is scientific and budgetary overlap with the current proposal and the pending R03 HL110786-01 proposal. In the event that both applications are approved, the respective funding agencies will be consulted, and either budgets will be modified to eliminate overlap or one of the awards will be declined.

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by abnormal thickening of blood vessel walls. Even with the best treatments, only about half of patients survive five years after diagnosis. This project will analyze the molecular and cellular pathways that different lung blood vessel cells follow to become abnormal in PAH, and identify new treatments that reverse these pathways and possibly cure patients. To accomplish this goal, we plan to study blood vessels from lungs removed from patients with PAH at the time they are undergoing lung or heart-lung transplant operations.

The information provided on the PHA website is provided for general information only. It is not intended as legal, medical or other professional advice, and should not be relied upon as a substitute for consultations with qualified professionals who are familiar with your individual needs.

801 Roeder Road, Ste. 1000, Silver Spring, MD 20910   Patient-to-Patient Support Line: 1-800-748-7274
Webmaster@PHAssociation.org
    Privacy Policy   Virtual Tour of Website    Provide Feedback & Report Bugs

Designed by Matrix Group International, Inc.® | © 2014 Pulmonary Hypertension Association. All Rights Reserved.

NORD

The National Organization for Rare Disorders (NORD) awarded PHA the Abbey S. Meyers Leadership Award in 2012 for outstanding service to PHA members in advocacy, education and other key areas.