Mani, Arya - Yale University - Biological & Biomedical Sciences

个人简介

My laboratory’s major focus is the identification of genetic causes of major cardiovascular disorders and the elucidation of their pathophysiology. Through collaborative efforts with physicians and scientist across the world we have recruited large populations of patients and families with early onset coronary artery disease and metabolic syndrome and have successfully mapped and identified number of genes for these diseases. An ongoing effort in the laboratory is to understand the function of these genes and how the mutations affect the phenotype, using mouse and zebrafish models. Having unique access to the genetic study population, we have had the opportunity to carry out clinical studies to investigate the disease mechanisms and have made numerous novel discoveries. We are actively investigating pathways that regulate insulin signaling, glucose metabolism, VLDL and LDL syntheis and clearance and atherosclerosis. In addition, my laboratory studies the genetic causes of adult congenital heart disease, such as bicuspid aortic valve, atrial fibrillation and patent ductus arteriosus. MD Johannes-Gutenberg-University of Mainz (1991) Fellow Yale University School of Medicine Resident Yale-New Haven Hospital Fellow University of Erlangen-Nuernberg Board Certification The Certification Board of Nuclear Cardiology, Nuclear Cardiology (2000) Board Certification AB of Internal Medicine, Cardiovascular Disease (2001, recertified: 2012) Board Certification National Board of Echocardiography, Adult Transthoracic Plus Stress Echocardiography (2008)

研究领域

Cardiology; Genetics; Heart; Heart Defects, Congenital

近期论文

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Rare nonconservative LRP6 mutations are associated with metabolic syndrome. Singh, R, Smith, E, Fathzadeh, M, Liu, W, Faramarzi,S, Subrahmanyan, L, Go, GW, McKenna, W and Mani, Rare nonconservative LRP6 mutations are associated with metabolic syndrome. Human Mutation, 2013 PMID: 23703864 LRP6 enhances glucose metabolism by promoting TCF7L2-dependent insulin receptor expression and IGF receptor stabilization in humans. Singh R, De Aguiar RB, Naik S, Mani S, Ostadsharif K, Wencker D, Sotoudeh M, Malekzadeh R, Sherwin RS, Mani A. Cell Metab. 2013 Feb 5;17(2):197-209. doi: 10.1016/j.cmet.2013.01.009. Low density lipoprotein (LDL) receptor-related protein 6 (LRP6) regulates body fat and glucose homeostasis by modulating nutrient sensing pathways and mitochondrial energy expenditure. Liu W, Singh R, Choi CS, Lee HY, Keramati AR, Samuel VT, Lifton RP, Shulman GI, Mani A. J Biol Chem. 2012 Mar 2;287(10):7213-23. doi: 10.1074/jbc.M111.286724. Epub 2012 Jan 9. Low-Density Lipoprotein Receptor (LDLR) Family Orchestrates Cholesterol Homeostasis. GO, GW, Mani A. Low-Density Lipoprotein Receptor (LDLR) Family Orchestrates Cholesterol Homeostasis. Yale J Biol Med. Mar ;85 (1):19-28 Lrp6 protein regulates low density lipoprotein (ldl) receptor-mediated ldl uptake. Ye ZJ, Go GW, Singh R, Liu W, Keramati AR, Mani A. Lrp6 protein regulates low density lipoprotein (ldl) receptor-mediated ldl uptake. J Biol Chem. 2012;287:1335-1344, PMC3256876 Wild-type LRP6 inhibits, whereas atherosclerosis-linked LRP6R611C increases PDGF-dependent vascular smooth muscle cell proliferation. Keramati AR, Singh R, Lin A, Faramarzi S, Ye Z, Mane S, Tellides G, Lifton RP, and Mani A. Wild-type LRP6 inhibits, whereas atherosclerosis-linked LRP6R611C increases PDGF-dependent vascular smooth muscle cell proliferation. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):1914-8. doi: 10.1073/pnas.1019443108. Epub 2011 Jan 18. The non-syndromic familial thoracic aortic aneurysms and dissections maps to 15q21 locus. Keramati, AR, Sadeghpour A, Farahani,M, Chandok G and Mani A. The non-syndromic familial thoracic aortic aneurysms and dissections maps to 15q21 locus. BMC Medical Genetics 2010, 11:143 Mutation in EGFP Domain of LDL Receptor-Related Protein 6 Impairs Cellular LDL Clearance. Mutation in EGFP Domain of LDL Receptor-Related Protein 6 Impairs Cellular LDL Clearance. Wenzhong Liu, Sheida Mani, Nicole R. Davis, Nizal Sarrafzadegan, Paula B. Kavathas, Arya Mani. Circulation Research. 2008103:1280-8. Bicuspid aortic valve: clinical approach and scientific review of a common clinical entity. Friedman T, Mani A, Elefteriades JA. Bicuspid aortic valve: clinical approach and scientific review of a common clinical entity.Expert Rev Cardiovasc Ther. 2008 Feb6(2):235-48. LRP6 mutation in a family with early coronary disease and metabolic risk factors. Mani A(Corresponding Author), Radhakrishnan J, Wang H, Mani A, Mani MA, Nelson-Williams C, Carew KS, Mane S, Najmabadi H, Wu D, Lifton RP. LRP6 mutation in a family with early coronary disease and metabolic risk factors.Science. 2007 Mar 2315(5816):1278-82. Syndromic patent ductus arteriosus: evidence for haplo insufficient TFAP2B mutations and identification of a linked sleep disorder. Mani A, Radhakrishnan J, Farhi A, Carew KS, Warne CA, Nelson-Williams C, Day RW, Pober B, State MW, Lifton RP. Syndromic patent ductus arteriosus: evidence for haplo insufficient TFAP2B mutations and identification of a linked sleep disorder. Proc Natl Acad Sci U S A 2005;102: 2975-2979. Nonalcoholic fatty liver disease induced by noncanonical Wnt and its rescue by Wnt3a. Wang S, Song K, Srivastava R, Dong C, Go GW, Li N1, Iwakiri Y, Mani A. Nonalcoholic fatty liver disease induced by noncanonical Wnt and its rescue by Wnt3a. FASEB 2015 A form of the metabolic syndrome associated with mutations in DYRK1B