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Alan R Shuldiner
 

Alan R Shuldiner M.D.

Academic Title: Professor
Primary Appointment: Medicine
Secondary Appointments: Physiology
Administrative Title: Division Head
Additional Title(s): John L. Whitehurst Endowed Professorship; Co-Director, University of Maryland Clinical and Translational Research Institute (CTSI); Head, Division of Endocrinology, Diabetes and Nutrition; Director, Program in Personalized and Genomic Medicine
ASHULDIN@medicine.umaryland.edu
Location: 685 West Baltimore Street, Room 379
Phone: (410) 706-1623

Personal History:

Alan R. Shuldiner received his BA degree (Chemistry) from Lafayette College (’79) and his MD degree from Harvard Medical School (’84). He was a resident in internal medicine at Columbia-Presbyterian Hospital in New York City and a Medical and Senior Staff Fellow in Endocrinology and Metabolism in the Diabetes Branch at the National Institutes of Health. Dr. Shuldiner is board certified in both Internal Medicine and Endocrinology and Metabolism. In 1991, he joined the faculty at Johns Hopkins University, Division of Geriatric Medicine and Gerontology as an Assistant Professor, and in 1993 he was promoted to Associate Professor. In 1997 he was recruited to the University of Maryland as Professor and Head of the Division of Diabetes, Obesity and Nutrition in the Department of Medicine. In 1999, the Division of Diabetes, Obesity and Nutrition and the Division of Endocrinology were combined, and Dr. Shuldiner assumed the leadership of the newly named Division of Endocrinology, Diabetes and Nutrition. Under his leadership the Division has grown to 34 full-time faculty members and an annual research budget of $13 million, ranking 11th in US News and World Report in 2013. In 2005, Dr. Shuldiner was named the John L. Whitehurst Professor of Medicine. In 2011, he was appointed Associate Dean for Personalized Medicine and Director of the interdepartmental program in Personalized and Genomic Medicine. In this context and also to expand infrastructure, quality and quantity of clinical and translational research, Dr. Shuldiner co-directs, with Dr. Stephen Davis, the University of Maryland Clinical and Translational Research Institute. He is also a Core Investigator at the Geriatric Research and Education Clinical Center (GRECC) at the Baltimore Veterans Administration Medical Center.

Research Interests:

Dr. Shuldiner’s major research interests lie in genetics of age-related diseases, including Type 2 diabetes (T2D), obesity, and cardiovascular disease - common disorders of aging that contribute significantly to mortality, morbidity, and health care costs in the United States and world-wide. He also works on the pharmaco- and nutri-genomics of these disorders. His vision is to make genomic discoveries that lead to more effective individualized treatment and prevention of these diseases (Personalized Medicine). Dr Shuldiner is best known for his studies in the Old Order Amish, a homogeneous founder population ideal for genetic studies. He leads a large multidisciplinary research team that uses state-of-the-art molecular genetic, statistical and epidemiological methods, including both candidate gene and genome wide approaches. Dr. Shuldiner’s group was the first to identify the Pro12Ala PPARG2 variant, a common functional susceptibility allele for T2D. He is a member of the Diabetes Prevention Program’s Genetics Group, the first group to replicate and extend into a prospective study the role of variants in TCF7L2 in T2D.  More recent genome-wide association studies (GWAS) in the Amish have uncovered novel mutations that have informed human biology and population genetics.  His group identified the first APOC3 null mutation in humans. Mutation carriers have low serum triglycerides, less coronary artery calcification, and are more likely to live past the age of 90 years. This genetic “proof-of-principle” experiment of nature validates apoCIII as a novel target for the treatment of hypertriglyceridemia and has provided the impetus for the initiation of apoCIII inhibitor programs at a number of pharmaceutical and biotechnology companies.  His group contributed to meta-GWAS studies of T2D, BMI, waist circumference, serum lipids, blood pressure, and other metabolic and cardiovascular traits. These studies, published in high-profile journals such as Nature, Nature Genetics, and AJHG identified more than 100 novel loci and genes for these complex traits. These loci promise to unveil new biology and potential targets for treatment and prevention of T2D and cardiovascular disease. Most recently, his group identified a common gene variant in CYP2C19 that is associated with poorer response to clopidogrel (Plavix). These findings along with candidate gene reports led to an FDA-mandated boxed warning on the package insert and recommendations for CYP2C19 genetic testing for more effective and individualized anti-platelet therapy in patients undergoing percutaneous coronary interventions and in patients with acute coronary syndromes.  His research has been supported continuously since 1995 by NIH and other competitive peer-reviewed foundation grants.

Dr Shuldiner has authored more than 250 original articles in leading journals and 60 reviews and book chapters. He is the recipient of a number of awards, including the prestigious Paul Beeson Physician Faculty Scholar award, the Ellison Medical Foundation Senior Scholar award, and the 2006 University of Maryland Founders Day Researcher of the Year award. Dr. Shuldiner serves on several steering and advisory committees (including NIDDK’s Scientific Council), and study sections related to his expertise in complex disease genetics and translation of genetic discoveries to the clinical setting.

Dr. Shuldiner is strongly committed to the training of young investigators in multidisciplinary patient-oriented research in aging, endocrinology and genetics research. He was PI of the UM-NIH Roadmap K12 Multidisciplinary Clinical Scholars Program designed to support the career development of more than 20 junior faculty.  Over the years, Dr. Shuldiner has mentored 18 predoctoral students, 26 postdoctoral trainees and 12 junior faculty, most of whom have pursued successful academic careers. 


Publications:

Search My Publications in Pub Med

HIGHLIGHTED PUBLICATIONS

Amish Family Diabetes Study

Hsueh W-C, Mitchell BD, Aburomia R, Sakul H, Ehm MG, Michelsen B, Wagner MJ, St. Jean PL, Knowler WC, Burns DK, Bell CJ, Shuldiner AR.  Diabetes in the Old Order Amish: characterization and heritability analysis of the Amish Family Diabetes Study.  Diab Care 23:595-601, 2000.

Hsueh W-C, Mitchell BD, Schneider JL, Wagner M, Bell CJ, Nanthakamur E, Shuldiner AR.  A QTL influencing blood pressure maps to the region of PPH1 on chromosome 2q31-34 in the Old Order Amish.  Circulation 101:2810-2816, 2000.

Hsueh W-C, Mitchell BD, Schneider JL, St. Jean PL, Pollin TI, Ehm MG, Wagner MJ, Burns DK, Bell CJ, Shuldiner AR.  Genome-wide scan of obesity and leptin levels in the Old Order Amish.  J Clin Endocrinol Metab 86:1199-1205, 2001.

Steinle N, Hsueh W-C, Snitker S, St. Jean PL, Sakul H, Ehm MG, Burns DK, Bell CJ, Mitchell BD, Shuldiner AR.  Eating behavior in the Old Order Amish: heritability analysis and a genome wide scan. Am J Clin Nutr 75:1098-106, 2002.

Allen EM, Hsueh W-C, Sabra MM, Pollin TI, Ladenson PW, Silver KD, Mitchell BD, Shuldiner AR.  A genome-wide scan for autoimmune thyroiditis in the Old Order Amish: Replication of genetic linkage on chromosome 5q11.2-q14.3.  J Clin Endocrinol Metab 88:1292-1296, 2003.

Hsueh W-C, St. Jean PL, Mitchell BD, Pollin TI, Knowler WC, Ehm MG, Bell CJ, Sakul H, Wagner MJ, Burns DK, Shuldiner AR.  Genome-wide and fine-mapping linkage studies of type-2 diabetes and glucose traits in the Old Order Amish: Evidence for a new diabetes locus on chromosome 14q11 and confirmation of a locus on chromosome 1q21-q24.  Diabetes 52:550-557, 2003.

Snitker S, Mitchell BD, Shuldiner AR.  Physical activity and prevention of type-2 diabetes (letter).  Lancet 361:87-88, 2003. 

Miura J, Pollin T, Hu Y, Notkins AL, Shuldiner AR.  Autoantibodies in type-1 and type-2 diabetes in the Old Order Amish of Pennsylvania  (2003) Diabetologia 46: 1024-1025, 2003.

Pollin TI, Hsueh W-C, Steinle NI, Snitker S, Shuldiner AR, Mitchell BD.  A genome-wide scan of lipid levels in the Old Order Amish. Atherosclerosis 173:89-96, 2004.

Rutherford S, Shuldiner AR, Mitchell BD.  Genome scans of type-2 diabetes mellitus.  Chapter 23 in: The International Textbook of Diabetes Mellitus (3rd ed.) E. Ferrannini, P. Zimmet, R. DeFronzo, H. Keen, Eds. J Wiley & Sons, W Sussex, UK, 2004.  pp. 439-450.

Damcott CM, Sack P, Shuldiner AR. The genetics of obesity. Endocrinol Metab Clin North Am 32:761-786, 2003.

Horenstein RB, Shuldiner AR.  Genetics of Diabetes  (2004)  In:  Genetics of Endocrine and Metabolic Disorders, LeRoith D, Levine M, Eds. Kluwer Academic Publishers, 2004, pp. 25-36. 

Steinle NI, Kazlauskaite R, Imumorin IG, Hsueh W-C, Pollin TI, Mitchell BD, Shuldiner AR.  Variation in the Lamin A/C (LMNA) Gene:  Associations with metabolic syndrome.  Arterio Thromb Vasc Biol 24:1708-13, 2004.

Snitker S, Shuldiner AR. BMI in the Old Order Amish. Med Sci Sports Exerc 36:1447, 2004.

Fu M, Damcott C, Sabra M, Pollin TI, Ott S, Wang J,  Garant M, O’Connell J, Mitchell BD, Shuldiner AR. Polymorphism in the Calsequestrin 1 gene on chromosome 1q21 is associated with type 2 diabetes in the Old Order Amish.  Diabetes (in press)

Damcott C, Hoppman N, Reinhart LJ, Wang J, O’Connell JR, Mitchell BD, Shuldiner AR. Polymorphisms in both promoters of hepatocyte nuclear factor 4-alpha are associated with type-2 diabetes in the Amish.  Diabetes (in press)

Pollin TI, Tanner K, O’Connell JR, Ott SH, Damcott CM, Shuldiner AR, McLenithan JC, Mitchell BD.  Linkage of plasma adiponectin levels to 3q27 explained by association with variation in the APM1 gene. Diabetes (in press)

Sabra M, Damcott C, Fu M, Ott S, O’Connell J, Mitchell BD, Shuldiner AR. Vesicle-associated membrane protein 4 (VAMP4), a positional candidate gene on 1q24-q25, is not associated with type 2 diabetes in the Old Order Amish.  Molec Genetics Metab (in press)

Damcott CM, Ott SH, Pollin TI, Reinhart LJ, Wang J, O’Connell JR, Mitchell BD, Shuldiner AR.  Genetic variation in adiponectin receptor 1 and adiponectin receptor 2 is associated with type-2 diabetes in the Old Order Amish.  (submitted)

Steinle NI, Pollin TI, O’Connell JR, Mitchell BD, Shuldiner AR.  Variants in the ghrelin gene are associated with metabolic syndrome and related traits in the Old Order Amish (submitted).

Rutherford S, Imumorin IG, O’Connell JR, Reinhart LJ, Pollin TI, Jian Wang J, Ott SH, Steine NI, Mitchell BD, Shuldiner AR.  Progress toward positional cloning of a gene influencing blood pressure on chromosome 2q31-q34 in the Amish.  (submitted, Hypertension) 

Amish Family Osteoporosis Study

Streeten EA, McBride DJ, Lodge A, Pollin T, Stinchcomb DG, Agarwala R, Schäffer AA, Shapiro JR, Shuldiner AR, Mitchell BD.  Osteoporosis in the Old Order Amish: A population at decreased risk for fracture.  J Bone Miner Res 19:308-313, 2004.

Brown LB, Streeten EA, Shuldiner AR, Almasy LA, Peyser PA, Mitchell BD.  Assessment of sex-specific genetic and environmental effects on bone mineral density.  Genetic Epid 27:153-161, 2004

Streeten EA, Ryan KA, McBride D, Pollin TI, Shuldiner AR, Mitchell BD.  The relation between parity and bone mineral density in women characterized by a homogeneous lifestyle and high parity.  (submitted)

Genetics of Longevity in the Amish

Steinle N, Shuldiner AR. The Old Order Amish: A unique model to study ageing. J Brit Menop Soc 6:127-128, 2000.

Mitchell BD, Hsueh W-C, King TM, Pollin TI, Sorkin J, Agarwala R, Schaffer AA, Shuldiner AR.  Heritability of life span in the Old Order Amish.  Am J Med Genet 102:346-352, 2001.

Sorkin J, Post W, Pollin TI, O’Connell JR, Mitchell BD, Shuldiner AR.  Exploring the genetics of longevity in the Old Order Amish.  Mechanisms of Ageing and Development.  The voyage to old age: searching for human longevity genes (in press)

Additional recent publications of importance to the field (in chronological order)

Walston J., Silver K., Bogardus C., Knowler W.S., Celi F.S., Austin S., Raben N., Manning B.StJ., Strosberg A.D., Sorkin J.D., Roth J., and Shuldiner A.R. Time of onset of non-insulin-dependent diabetes mellitus and genetic variation in the 3-adrenergic–receptor gene (1995) N. Engl. J. Med. 333, 343-347. PMID: 7609750.

Barzilai N., Atzmon G., Schechter C., Schaefer E.J., Cupples A.L., Lipton R., Cheng S., Shuldiner A.R.  Unique lipoprotein phenotype and genotype associated with exceptional longevity (2003) JAMA 290, 2030-2040. PMID: 14559957. 

Florez J.C., Jablonski K.A., Bayley N., Pollin T.I., de Bakker P.I., Shuldiner A.R., Knowler W.C., Nathan D.M., Altshuler D. for the Diabetes Prevention Program Research Group. TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program (2006) N. Engl. J. Med. 355, 241-250. PMID: 16855264. 

Damcott C.M., Pollin T.I., Reinhart L.J., Ott S.H., Shen H., Silver K.D., Mitchell B.D., Shuldiner A.R. Polymorphisms in the transcription factor 7-like 2 (TCF7L2)gene are associated with type 2 diabetes in the Amish: Replication and evidence for a role in both insulin resistance and insulin secretion (2006) Diabetes 55, 2654-2659. 

Rampersaud E., Damcott C.M., Fu M., Shen H., McArdle P., Shi X., Shelton J., Yin J., Chang C.Y., Ott S.H., Zhang L., Zhao Y., Mitchell B.D., O’Connell J.O., Shuldiner A.R. Identification of novel candidate genes for type 2 diabetes from a genome-wide association scan in the Old Order Amish: Evidence for replication from diabetes-related quantitative traits and from independent populations (2007) Diabetes 56, 3053-3062. PMID: 17846126

Mitchell B.D., McArdle P.F., Shen H., Rampersaid E., Pollin T.I., Bielak L.F., Jaquish C., Douglas J.A., Roy-Gagnon M.H., Sack P., Naglieri R., Hines S., Horenstein R.B., Chang Y-.P.C. Post W., Ryan K.A., Sorkin J., Damcott C.M., O’Connell J.R., Corretti M., Vogel R., Herzog W., Weir M.R., Peyser P.A., Shuldiner A.R. The genetic response to short-term interventions affecting cardiovascular function:  Rationale and design of the HAPI Heart Study (2008) Am. Heart J. 155, 823-828. PMCID: PMC2443415.

Pollin T.I., Damcott C.M., Shen H., Ott S.H., Shelton J., Horenstein R.B., Post W., McLenithan J.C., Bielak L.F., Peyser P.A., Mitchell B.D., Miller M., O’Connell J.R., Shuldiner A.R. A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection (2008) Science 322, 1702-1705. PMCID: PMC2673993

Shuldiner A.R., O’Connell J.O., Bliden K.P., Gandhi A., Ryan K., Horenstein R.B., Damcott C.M., Pakyz R., Gibson Q., Pollin T.I., Post W., Parsa A., Mitchell B.D., Faraday N., Herzog W., Gurbel P.A. Cytochrome p450 2C19 genotype is a major determinant of the anti-platelet effect and clinical efficacy of clopidogrel therapy (2009) JAMA 302, 849-858. PMID 19706858.

Dupuis J., Lannberg C., Prokopenko I., Saxena R., Soranzo N….Shuldiner A.R.…. Boehnke M., McCarthy M.I., Florez J.C. and Barroso I. for the MAGIC investigators. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk (2010) Nat. Genet. 42, 105-116.PMID: 20081858. 

Shen H., Damcott C.M., Rampersaud E., Pollin T.I., O’Connell J.O., Horenstein R.B., McArdle P.F., Peyser P.A., Bielak L.F., Post W., Chang Y.-P. C. Ryan K.A., Miller M., Shelton J., Shuldiner A.R., Mitchell B.D. Apolipoprotein B (APOB) R3500Q is common in the Old Order Amish and is a major cause of increased low density lipoprotein cholesterol concentrations and coronary artery calcification (2010) Arch. Int. Med. 170, 1850-1855. PMID: 21059979

Gieger C., Radhakrishnan A., Cvejic A., Tang W., Porcu E., Pistis G.,..125 other authors…Shuldiner A.R.,…30 other authors…Ouwehand W.H., Soroanzo N. New gene functions in megakaryopoiesis and platelet formation (2011) Nature 480, 201-208. PMID: 22139419.

Lewis J.P., Fisch A.S., Ryan K., O'Connell J.R., Gibson Q., Mitchell B.D., Shen H., Tanner K., Horenstein R.B., Pakzy R., Tantry U.S., Bliden K.P., Gurbel P.A., Shuldiner A.R. Paraoxonase 1 (PON1) gene variants are not associated with clopidogrel response (2011) Clin. Pharmacol. Ther. 90, 568-574.

Liu J., Hoppman N., O'Connell J.R., Wang H., Streeten E.A., McLenithan J.C., Mitchell B.D., Shuldiner A.R. A functional haplotype in EIF2AK3, an ER stress sensor, is associated with lower bone mineral density (2012) J. Bone. Miner. Res. 27, 331-41. PMID: 22028037

Zupancic M.L., Cantarel B.L., Liu Z., Drabek E.F., Ryan K.A., Cirimotich S., Jones C., Knight R., Walters W.A., Knights D., Mongodin E.F., Horenstein R.B., Mitchell B.D., Steinle N., Snitker S., Shuldiner A.R., Fraser C.M. Analysis of the gut microbiota in the Old Order Amish and its relation to the metabolic syndrome (2012) PLoS ONE 7(8), e43052.  PMID: 22905200

Lewis J.P., Ryan K., O'Connell J.R., Horenstein R.B., Damcott C.M., Gibson Q., Pollin T.I., Mitchell B.D., Beitelshees A.L., Pakzy R., Tanner K., Parsa A., Tantry U.S., Bliden K.P., Post W.S., Faraday N., Herzog W., Gong Y., Pepine C.J., Johnson J.A., Gurbel P.A., Shuldiner A.R. Genetic Variation in PEAR1 is associated with platelet aggregation and cardiovascular outcomes (2013) Circ. Cardiovasc. Genet. 1, 184-92. PMID: 23392654