Arya Mani

Associate Professor of Medicine and Cardiology
Section of Cardiovascular Medicine

Research Interests

Despite our recent advances in Cardiovascular Medicine, the cardiovascular disease remains the leading cause of death in the world. With the break through brought about by The Human Genome project, we are now in a unique position to dissect the genetic causes of cardiovascular diseases to better understand the pathways that lead to disease in human and subsequently try to find therapies tailored to the specific genetic abnormality.

My interest is to identify cardiovascular disorders that have strong familial pattern. We identify kindreds with these disorders and collect DNA samples from the extended family members to proceed with the technique of positional cloning to identify the disease-causing genes.

Thus far, I, and my colleagues have mapped and identified several gene mutation for congenital heart diseases including patent ductus arteriosus and bicuspid aortic valve. Recently my group identified a gene mutation in LRP6, a co-receptor for Wnt, in a kindred with coronary artery disease and several metabolic phenotypes. We have shown that the mutation impairs a signaling pathway known as Wnt. We have created knockin and knockout mouse models of this gene and are conducting in vivo and in vitro functional studies using human cells, in vitro transfection models, human clinical studies as well as studies on lipid and glucose metabolism in mice in collaboration with Dr. Gerald Shulman, The GCRC, and The Mouse Metabolic Phenotyping Center. We are also investigating the genetic causes of premature coronary artery disease in South Asians. South Asians suffer largely from coronary artery disease in young ages and have high risk for developing diabetes, a constellation of phenotypes commonly referred to as metabolic syndrome. Our preliminary data suggests, that we have identified at least one gene locus for this disorder. We are currently collaborating with several medical centers across the world and in India to recruit new families and individuals with premature coronary artery disease with or without metabolic syndrome to refine the mapped region and identify the gene mutation.

We use several different techniques in our laboratory, which includes positional cloning using DNA microarrays, techniques used for protein chemistry, subcloning, tissue culture, confocal microscopy, FACS, real time PCR and animal model.

For those interested for rotation or extended experience in the lab can contact Wenzhong Liu at 785-6055 or email me at arya.mani@yale.edu.

Mani A, Matovcik L, Gorelick FC. The intracellular distribution of mannose 6-phosphate receptor (M-6PR) during cerulein induced pancreatitis. AFCR 1993.

Nathanson MH, Burgstahler AD, Orloff JJ, Mani A, Moyer MS. Mechanism of desensitization of the cloned vasopressin V1a receptor expressed in Xenopus oocytes. Am J Physiol. 267: C94-103, 1994.

Mani A, Krumholz H, Lifton RP. The inheritance of congenital bicuspid aortic valve. Circulation 98:I-597.

Mani A, Lynch HT, Begleiter ML, Porter TR, Rezaie T, Lifton RP. 1998. Mapping a gene for autosomal dominant patent ductus arteriosus. Circulation 98: I-596.

Mani A, Houshyar R, Mani A, Ahangar M, Meeraji M, Lifton RP. A New Recessive Form of Patent Ductus Arteriosus Maps to 12q24. Circulation Vol 104, 17:II-668, 2001.

Mani A, Meraji S, Houshyar R, Radhakrisnan J, Mani A, Ahangar M, Rezaie TM, Taghavi-nejad M, Broumand B, Zhao H, Nelson-Williams C, Lifton RP. Finding genetic contributions to sporadic disease: A recessive locus at 12q24 commonly contributes to patent ductus arteriosus. PNAS 2002.(99):15054-15059.

Mani A, Radhakrishnan J, Farhi A, Nelson-Williams C, Warnes, Lifton RP. Novel splice-site mutation may suggest an alternative mechanism and expands the phenotypic range of disease in a gene for hand heart syndrome. In preparation.

Mani A, Radhakrishnan J, Farhi A, Carew KS, Warnes CA, Nelson-Williams C, Day RW, Pober B, State MW, Lifton RP. Syndromic patent ductus arteriosus: evidence for haploinsufficient TFAP2B mutations and identification of a linked sleep disorder. Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2975-9.

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 2;315(5816):1278-82.

Friedman T, Mani A, Elefteriades JA. Bicuspid aortic valve: clinical approach and scientific review of a common clinical entity.Expert Rev Cardiovasc Ther. 2008 Feb;6(2):235-48.

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. 2008;103:1280-8.

Education:	B.S., Pahlavi University, Shiraz, 1984 M.D., Johannes Gutenberg University, Mainz, 1991
Training:	Fellow: Clinical Nephrology, University of Erlangen-Nuernberg, 1991-1992 Postdoctoral Fellowship: Cell Biology and Gastroenterology, Yale University School of Medicine, 1992-1993 Intern and Resident: Internal Medicine, Yale-New Haven Hospital, Yale University School of Medicine, 1993-1996 Chief Resident: Internal Medicine, Yale University School of Medicine, 1996-1997 Fellow: Cardiology, Yale University, 1999-2001
Prior Academic Positions:	Associate Research Scientist: Yale University School of Medicine, 1997-1999 Instructor in Medicine: Yale University School of Medicine, 2001-2003

Contact

Campus Address
Department of Internal Medicine
Section of Cardiovascular Medicine
Yale University
School of Medicine
Box 208017
New Haven, CT
06520-8017

E-mail
arya.mani@yale.edu

Telephone
203.785.4114