Dr. Ferhaan Ahmad |
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University of Pittsburgh School of Medicine Medicine Cardiovascular Institute Assistant ProfessorAppointed: 2005 University of Pittsburgh Graduate School of Public Health Human Genetics Assistant ProfessorAppointed: 2005 University of Pittsburgh Medical Center Medicine Cardiovascular Institute, Cardiovascular Genetics Center DirectorAppointed: 2005 |  |
Mailing Address200 Lothrop Street Scaife Hall, Room S-558 Pittsburgh, Pennsylvania 15213-2582United States | Contact InformationPhone: (412) 648-9286 Fax: (412) 647-4227 ahmadf@upmc.edu http://www.dept-med.pitt.edu/card/genetics.html |
Qualifications
Postdoctoral Fellowship, Harvard University/Howard Hughes Medical Institute, Genetics, 2005.
Ph.D., Baylor College of Medicine, Cardiovascular Sciences, 2001.
Fellowship, McGill University, Cardiovascular Disease, 1996.
Residency, McGill University, Internal Medicine, 1994.
M.D., McGill University, Medicine, 1991.
Expertise and Research Interests
Clinical and Research Interests:
Hypertrophic cardiomyopathy
Dilated cardiomyopathy
Arrhythmogenic right ventricular dysplasia
Glycogen storage cardiomyopathy
Pulmonary arterial hypertension
Congenital heart disease
Genetic causes of heart failure and sudden cardiac death
Dr. Ahmad is trained clinically as a noninvasive cardiologist, with additional certification in nuclear cardiology, and scientifically as a molecular geneticist. He has a special interest in patients with inherited cardiovascular diseases, such as hypertrophic and dilated cardiomyopathies, arrhythmogenic right ventricular dysplasia, glycogen storage cardiomyopathy, pulmonary arterial hypertension, familial congenital heart disease, and ion channelopathies. He is the Director of the Cardiovascular Genetics Center, where patients with inherited cardiovascular diseases and their relatives are evaluated, treated, and counseled.
This research is dependent on crosstalk between clinical studies, human molecular genetic studies, animal modeling, and basic cellular and molecular studies. The laboratory welcomes collaborations with patients, clinicians, and scientists, and actively seeks patients and families with inherited cardiovascular disorders who may be interested in participating in this research.
Postdoctoral fellows and medical and graduate students in the laboratory are exposed to a breadth of techniques in statistical genetics, molecular genetics, molecular and cell biology, biochemistry, and physiology. They have the opportunity to pursue projects with clinical or basic orientations, within a multidisciplinary "bedside to bench to bedside" environment.
A selection of current projects is described below:
Genetic linkage analysis and positional candidate gene analysis are being performed in several human families with ARVD. We are studying the structural changes that characterize right ventricular myocardium in ARVD.
In collaboration with Michael Barmada, PhD, we are using a highly innovative technique to merge transcriptional genomics and genetics to elucidate the pathogenesis of pulmonary arterial hypertension and secondary right heart failure.
The phenotype and clinical outcome of patients with cardiomyopathies vary greatly, even among members of the same family with the same mutation. Therefore, we are recruiting cardiomyopathy patients and studying whether polymorphisms in candidate modifier genes (genes other than those with the primary causative mutation) can alter the cardiac phenotype, response to therapy, and survival.
Different mutations in several genes, including cardiac troponin T (TNNT2), can lead to both DCM and HCM. We have generated gene targeted ("knock-in") mouse models of several TNNT2 mutations and are performing analyses to determine how mutations in the same gene lead to distinct phenotypes. Preliminary evidence suggests that DCM-and HCM-associated mutations lead to divergent early changes in cardiac contractility and calcium (Ca2+) sensitivity at the molecular and cellular level prior to evident changes at the whole organ level. Therefore, we and our collaborators Michael Mathier, MD, and Sanjeev Schroff, PhD, are performing echocardiography, in vivo hemodynamic measurements, and biomechanical studies on cardiac myocytes, isolated hearts, and/or intact mice to uncover divergent effects of these mutations on contractility. A second hypothesis is that, as a mediator of Ca2+ regulation in the sarcomere, TNNT2 mutations cause perturbations in Ca2+ levels and transients and/or action potential propagation, leading to hypertrophy, systolic or diastolic dysfunction, and/or arrhythmias. Therefore, in collaboration with Samir Saba, MD, and Guy Salama, PhD, we are performing in vivo electrophysiological studies and optical mapping using voltage-sensitive dyes.
We and others have recently identified mutations in the gene PRKAG2 as the cause for a novel cardiomyopathy characterized by glycogen storage and ventricular preexcitation. This gene encodes the regulatory alpha2 subunit of AMP-activated protein kinase (AMPK), a heterotrimeric enzyme which activates several processes to conserve and to generate energy when cellular energy levels are depleted. We have constructed transgenic mouse models of human PRKAG2 mutations and are studying the pathogenesis of PRKAG2 cardiomyopathy in these models, determining which cardiac AMPK targets are altered by the PRKAG2 mutations.
We are currently constructing other gene targeted mouse models of human cardiomyopathies.
Hypertrophic cardiomyopathy
Dilated cardiomyopathy
Arrhythmogenic right ventricular dysplasia
Glycogen storage cardiomyopathy
Pulmonary arterial hypertension
Congenital heart disease
Genetic causes of heart failure and sudden cardiac death
Dr. Ahmad is trained clinically as a noninvasive cardiologist, with additional certification in nuclear cardiology, and scientifically as a molecular geneticist. He has a special interest in patients with inherited cardiovascular diseases, such as hypertrophic and dilated cardiomyopathies, arrhythmogenic right ventricular dysplasia, glycogen storage cardiomyopathy, pulmonary arterial hypertension, familial congenital heart disease, and ion channelopathies. He is the Director of the Cardiovascular Genetics Center, where patients with inherited cardiovascular diseases and their relatives are evaluated, treated, and counseled.
This research is dependent on crosstalk between clinical studies, human molecular genetic studies, animal modeling, and basic cellular and molecular studies. The laboratory welcomes collaborations with patients, clinicians, and scientists, and actively seeks patients and families with inherited cardiovascular disorders who may be interested in participating in this research.
Postdoctoral fellows and medical and graduate students in the laboratory are exposed to a breadth of techniques in statistical genetics, molecular genetics, molecular and cell biology, biochemistry, and physiology. They have the opportunity to pursue projects with clinical or basic orientations, within a multidisciplinary "bedside to bench to bedside" environment.
A selection of current projects is described below:
Genetic linkage analysis and positional candidate gene analysis are being performed in several human families with ARVD. We are studying the structural changes that characterize right ventricular myocardium in ARVD.
In collaboration with Michael Barmada, PhD, we are using a highly innovative technique to merge transcriptional genomics and genetics to elucidate the pathogenesis of pulmonary arterial hypertension and secondary right heart failure.
The phenotype and clinical outcome of patients with cardiomyopathies vary greatly, even among members of the same family with the same mutation. Therefore, we are recruiting cardiomyopathy patients and studying whether polymorphisms in candidate modifier genes (genes other than those with the primary causative mutation) can alter the cardiac phenotype, response to therapy, and survival.
Different mutations in several genes, including cardiac troponin T (TNNT2), can lead to both DCM and HCM. We have generated gene targeted ("knock-in") mouse models of several TNNT2 mutations and are performing analyses to determine how mutations in the same gene lead to distinct phenotypes. Preliminary evidence suggests that DCM-and HCM-associated mutations lead to divergent early changes in cardiac contractility and calcium (Ca2+) sensitivity at the molecular and cellular level prior to evident changes at the whole organ level. Therefore, we and our collaborators Michael Mathier, MD, and Sanjeev Schroff, PhD, are performing echocardiography, in vivo hemodynamic measurements, and biomechanical studies on cardiac myocytes, isolated hearts, and/or intact mice to uncover divergent effects of these mutations on contractility. A second hypothesis is that, as a mediator of Ca2+ regulation in the sarcomere, TNNT2 mutations cause perturbations in Ca2+ levels and transients and/or action potential propagation, leading to hypertrophy, systolic or diastolic dysfunction, and/or arrhythmias. Therefore, in collaboration with Samir Saba, MD, and Guy Salama, PhD, we are performing in vivo electrophysiological studies and optical mapping using voltage-sensitive dyes.
We and others have recently identified mutations in the gene PRKAG2 as the cause for a novel cardiomyopathy characterized by glycogen storage and ventricular preexcitation. This gene encodes the regulatory alpha2 subunit of AMP-activated protein kinase (AMPK), a heterotrimeric enzyme which activates several processes to conserve and to generate energy when cellular energy levels are depleted. We have constructed transgenic mouse models of human PRKAG2 mutations and are studying the pathogenesis of PRKAG2 cardiomyopathy in these models, determining which cardiac AMPK targets are altered by the PRKAG2 mutations.
We are currently constructing other gene targeted mouse models of human cardiomyopathies.
Future Research
Our research is dependent on crosstalk between clinical studies, human molecular genetic studies, animal modeling, and basic cellular and molecular studies. We welcome collaborations with other clinicians and scientists, and are actively seeking patients and families with inherited cardiovascular disorders who may be interested in participating in our research.
Keywords
COS Keywords:
Animal Models, Cardiology, Cardiomyopathy, Cardiovascular Diseases, Congenital Heart Disease, Genetics, Heart, Mutation, Phenotype.Additional Terms:
Arrhythmias, Arrhythmogenic Right Ventricular Dysplasia, Cardiomyopathies, Congenital Heart Disease, Dilated Cardiomyopathy, Gene Expression, Genetics, Genomics, Glycogen Storage Cardiomyopathy, Heart Failure, Hypertrophic Cardiomyopathy, Mouse Models, Pulmonary Arterial Hypertension, Sudden Cardiac Death.Languages
(Reading, Writing, Speaking)
English: (Fluent, Fluent, Fluent)
French: (Fluent, Fluent, Fluent)
Memberships
American Heart Association
Canadian Cardiovascular Society
College of Physicians and Surgeons of Ontario
Royal College of Physicians and Surgeons of Canada
Honors and Awards
1999, Young Investigator Awards Finalist,
American College of Cardiology
1999, Overall Award for Excellence in Research,
National Student Research Forum,
University of Texas Medical Branch at Galveston
1996-2002,
Clinician Scientist Award,
Canadian Institutes of Health Research (CIHR)
Previous Positions
2001-2005, Fellow,
Brigham and Women's Hospital,
Medicine,
Cardiovascular
2001-2005, Research Associate,
Harvard University,
Medical School,
Genetics,
Howard Hughes Medical Institute
1996-2001, Fellow,
The Texas A&M Health Science Center,
Baylor College of Medicine,
Medicine,
Medicine
1994-1996, Fellow,
McGill University,
Faculty of Medicine,
Medicine,
Cardiology
1991-1994, Resident,
McGill University,
Faculty of Medicine,
Medicine
Funding Received
- Doris Duke Charitable Foundation Clinical Scientist Development Award: Identification of the Genetic Determinants of ARVD, 2006 to 2009.
- Samuel and Emma Winters Foundation: Identification of Genetic Modifiers of Hypertrophic Cardiomyopathy (HCM), 2006 to 2007.
- American Heart Association Scientist Development Grant: Elucidating the Pathogenesis of Cardiomyopathies Using Mouse Genetic Strategies, 2005 to 2009.
- Canadian Institutes of Health Research (CIHR): Identification of Genes Responsible for Arrhythmogenic Right Ventricular Dysplasia, 1996 to 2002.
Publications
- Banerjee SK, Ramani R, Saba S, Rager J, Tian R, Mathier MA, Ahmad F (2007) A PRKAG2 mutation causes biphasic changes in myocardial AMPK activity and does not protect against ischemia, Biochem Biophys Res Commun, In Press
- Schmitt JP, Debold EP, Ahmad F, Armstrong A, Frederico A, Conner D, Mende U, Lohse MJ, Warshaw D, Seidman CE, Seidman JG (2006) Cardiac myosin missense mutations cause dilated cardiomyopathy in mouse models and depress molecular motor function, Proc Natl Acad Sci, 103, 14525-14530
- 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 (Nov 2005) Increased alpha2 subunit-associated AMPK activity and PRKAG2
cardiomyopathy., Circulation, 112 (20), 3140-8
- Musi N, Hirshman MF, Arad M, Xing Y, Fujii N, Pomerleau J, Ahmad F, Berul CI, Seidman JG, Tian R, Goodyear LJ (Apr 2005) Functional role of AMP-activated protein kinase in the heart during
exercise., Febs Letters, 579 (10), 2045-50
- Arany Z, He H, Lin J, Hoyer K, Handschin C, Toka O, Ahmad F, Matsui T, Chin S, Wu PH, Rybkin II, Shelton JM, Manieri M, Cinti S, Schoen FJ, Bassel-Duby R, Rosenzweig A, Ingwall JS, Spiegelman BM (Apr 2005) Transcriptional coactivator PGC-1 alpha controls the energy state and
contractile function of cardiac muscle., Cell Metab, 1 (4), 259-71
- Ahmad F, Seidman JG, Seidman CE (2005) The genetic basis for cardiac remodeling., Annual Review of Genomics and Human Genetics, 6, 185-216
- Schmitt JP, Semsarian C, Arad M, Gannon J, Ahmad F, Duffy C, Lee RT, Seidman CE, Seidman JG (Sep 2003) Consequences of pressure overload on sarcomere protein mutation-induced
hypertrophic cardiomyopathy., Circulation, 108 (9), 1133-8
- Ahmad F, The Molecular Genetics of Arrhythmogenic Right Ventricular Dysplasia-cardiomyopathy, Clinical and Investigative Medicine. Medecine Clinique Et Experimentale, 26(4), 167-78, Aug 2003
- Arad M, Moskowitz IP, Patel VV, Ahmad F, Perez-Atayde AR, Sawyer DB, Walter M, Li GH, Burgon PG, Maguire CT, Stapleton D, Schmitt JP, Guo XX, Pizard A, Kupershmidt S, Roden DM, Berul CI, Seidman CE, Seidman JG, Transgenic Mice Overexpressing Mutant PRKAG2 Define the Cause Of Wolff-Parkinson-White Syndrome in Glycogen Storage Cardiomyopathy, Circulation, 107(22), 2850-6, Jun 2003
- Arad M, Moskowitz IP, Patel VV, Ahmad F, Perez-Atayde AR, Sawyer DB, Walter M, Li GH, Burgon PG, Maguire CT, Stapleton D, Schmitt JP, Guo XX, Pizard A, Kupershmidt S, Roden DM, Berul CI, Seidman CE, Seidman JG (Jun 2003) Transgenic mice overexpressing mutant PRKAG2 define the cause of
Wolff-Parkinson-White syndrome in glycogen storage
cardiomyopathy., Circulation, 107 (22), 2850-6
- Grabie N, Delfs MW, Westrich JR, Love VA, Stavrakis G, Ahmad F, Seidman CE, Seidman JG, Lichtman AH, IL-12 Is Required for Differentiation of Pathogenic CD8+ T Cell Effectors That Cause Myocarditis, The Journal of Clinical Investigation, 111(5), 671-80, Mar 2003
- Grabie N, Delfs MW, Westrich JR, Love VA, Stavrakis G, Ahmad F, Seidman CE, Seidman JG, Lichtman AH (Mar 2003) IL-12 is required for differentiation of pathogenic CD8+ T cell effectors
that cause myocarditis., The Journal of Clinical Investigation, 111 (5), 671-80
- 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, 299(5611), 1410-3, Feb 2003
- Schmitt JP, Kamisago M, Asahi M, Li GH, Ahmad F, Mende U, Kranias EG, MacLennan DH, Seidman JG, Seidman CE (Feb 2003) Dilated cardiomyopathy and heart failure caused by a mutation in
phospholamban., Science, 299 (5611), 1410-3
- Natarajan A, Yamagishi H, Ahmad F, Li D, Roberts R, Matsuoka R, Hill S, Srivastava D, Human EHAND, But Not DHAND, Is Down-regulated in Cardiomyopathies, Journal of Molecular and Cellular Cardiology, 33(9), 1607-14, Sep 2001
- Gollob MH, Green MS, Tang AS, Gollob T, Karibe A, Ali Hassan AS, Ahmad F, Lozado R, Shah G, Fananapazir L, Bachinski LL, Roberts R, Hassan AS, Identification of a Gene Responsible for Familial Wolff-Parkinson-White Syndrome, The New England Journal of Medicine, 344(24), 1823-31, Jun 2001
- 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, 70(3), 347-53, Dec 2000
- 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, American Journal of Human Genetics, 66(1), 148-56, Jan 2000
- Ahmad F, Seidman JG, Seidman CE, The Genetic Basis for Cardiac Remodeling, Annual Review of Genomics and Human Genetics, 6, In Press, 2000
- 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 to Chromosome 3p23, Circulation, 98(25), 2791-5, Dec 1998
- Ahmad F, Solymoss S, Poon MC, Berube C, Sullivan AK, Characterization of An Acquired IgG Inhibitor of Coagulation Factor XIII in a Patient With Systemic Lupus Erythematosus, British Journal of Haematology, 93(3), 700-3, Jun 1996
- Fantus IG, Ahmad F, Deragon G, Vanadate Augments Insulin-stimulated Insulin Receptor Kinase Activity And Prolongs Insulin Action in Rat Adipocytes. Evidence for Transduction Of Amplitude of Signaling Into Duration of Response, Diabetes, 43(3), 375-83, Mar 1994
- Tuite P, Ahmad F, Grant I, Stewart JD, Carpenter S, Ethier R, Cerebral Vein Thrombosis Due to Hereditary Antithrombin III Deficiency, The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques., 20(2), 158-61, May 1993
- Ahmad F, Anencephalic Infants As Organ Donors: Beware the Slippery Slope, Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne., 146(2), 236-41, 244, Jan 1992
- Fantus IG, Ahmad F, Deragon G, Vanadate Augments Insulin Binding and Prolongs Insulin Action in Rat Adipocytes, Endocrinology, 127(6), 2716-25, Dec 1990
Profile Details
Last Verified: 6/9/2007
COS Expertise ID #1194854
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