Maria Kontaridis Laboratory
Maria Kontaridis, PhD
Cardiovascular Research Cardiovascular
Division Beth Israel Deaconess Medical Center 3 Blackfan Circle
E/CLS #908 Boston MA 02215
Dr. Kontaridis received her undergraduate degrees (B.A. and B.S.) from the University of Florida in Classics and Chemistry, and subsequently, went on to obtain her masters degrees in Pharmacology as well as Biomedical and Biological Sciences from Yale University in 1999 and 2001, respectively. In 2002, she was awarded a Ph.D. from Yale University for work with Dr. Anton Bennett on the role of protein tyrosine phosphatases, especially SHP-2, in cell growth and skeletal muscle differentiation. Dr. Kontaridis' interest in continuing to work on SHP-2 phosphatase led her to accept a postdoctoral position with Dr. Benjamin Neel, at the BIDMC in 2003. Her work as a postdoctoral fellow garnered extramural support from the American Heart Association and the NIH Pathway to Independence Award (K99/R00). In 2007, Dr. Kontaridis was promoted to Instructor, and in 2008, was recruited to the Department of Medicine, Division of Cardiology at BIDMC as an Assistant Professor of Medicine at Harvard Medical School. In this context, Dr. Kontaridis has made multiple interesting observations about SHP-2 and its role in cardiac pathophysiology and disease. Her work has been awarded grants from the Milton Foundation, the Children’s Cardiomyopathy Foundation, the Saving Tiny Hearts Foundation, the Harvard Stem Cell Institute, the Alliance of Lupus Research and the National Institutes of Health (NHLBI-R01 and NCATS-TRND).
Dr. Kontaridis is actively involved in the BIDMC/Cardiology division as co-organizer of the departmental seminar series and the annual Cardiology Retreat. She is also a member of the Cardiology Fellowship Selection Committee, serves as a member of the Committee for the Advancement of Women Faculty in the Department of Medicine, and is Chairman of the Research Safety Committee at BIDMC. Dr. Kontaridis is also a member of the Harvard Medical School Biomedical and Biological Sciences Faculty Program, where she has a joint appointment in the department of Biological Chemistry and Molecular Pharmacology and with the Leder Human Biology and Translational Medicine Program of Harvard Medical School. In December of 2010, Dr. Kontaridis was appointed Fellow of the American Heart Association.
Understanding the signaling pathways that mediate cardiac developmental processes may reveal important clues into the cellular and molecular pathogenesis of heart disease. Our research program focuses on the fundamental mechanisms underlying both congenital heart disease and end-stage heart failure, and the mechanisms therein that lead to abnormal development, aberrant molecular signaling, and disease onset. Our lab uses a myriad of tools and techniques including iPS cells, in vivo mouse model systems, and molecular biology techniques. Together, these provide valuable mechanistic and functional information in understanding the differential signaling pathways and developmental processes leading to cardiac disease. Specifically, we want to understand how protein-tyrosine phosphatases (PTPs) relate to cardiac development and disease. Our lab has three main interests: 1) elucidation of the cardiomyogenic defects associated with Noonan and LEOPARD Syndromes, two autosomal dominant congenital disorders primarily caused by unique mutations in the protein tyrosine phosphatase SHP2; 2) understanding the functional role and mechanisms by which SHP2 activity is involved in the development of Systemic Lupus Erythematosus; and 3) elucidating the potential cardioprotective effects of the small G protein RhoA in the adult heart through identification of novel signaling pathways involved in cardiac pathogenesis.
1-Lauriol, J, Keith, K, Jaffre, F, Couvillon, A, Saci, A, Goonasekera, SA, McCarthy, JR, Kessinger, CW, Wang, J, Ke, Q, Kang, P, Molkentin, JM, Carpenter, C, and Kontaridis, MI. RhoA signaling in cardiomyocytes protects against stress-induced heart failure. Sci Signal. 2014 Oct 21;7(348):ra100. doi: 10.1126/scisignal.2005262.
2-Talita M. Marin, Kimberly Keith, Benjamin Davies, David A. Conner, Prajna Guha, Demetrios Kalaitzidis, Xue Wu , Michael Bauer, Roderick Bronson, Kleber G. Franchini, Benjamin G. Neel and Maria I. Kontaridis. Rapamycin normalizes hypertrophic cardiomyopathy in a mouse model of LEOPARD Syndrome-associated PTPN11 mutation. JCI, 2011 Feb 21. pii: 44972. doi: 10.1172/JCI44972.
3-Stewart RA, Sanda T, Widlund HR, Zhu S, Swanson KD, Hurley AD, Bentires-Alj M, Fisher DE, Kontaridis MI, Look AT, Neel BG. Phosphatase-Dependent and -Independent Functions of Shp2 in Neural Crest Cells Underlie LEOPARD Syndrome Pathogenesis. Dev Cell. 2010 May 18;18(5):750-762.
4-Kontaridis MI, Yang W, Bence KK, Cullen D, Wang B, Bodyak N, Ke Q, Hinek A, Kang PM, Liao R, Neel BG. Deletion of Ptpn11 (Shp2) in cardiomyocytes causes dilated cardiomyopathy via effects on the extracellular signal-regulated kinase/mitogen-activated protein kinase and RhoA signaling pathways. Circulation. 2008;117(11):1423-35. Editorial: Shp Shape - FAKs about hypertrophy, Martin, KA, Hwa, J., Circ Res. 2008 October 10; 103(8): 776-778
5-Kontaridis MI, Swanson KD, David FS, Barford D, Neel BG. PTPN11 (Shp2) mutations in LEOPARD syndrome have dominant negative, not activating, effects. J Biol Chem. 2006;281(10):6785-92. 5-Bentires-Alj, M., Kontaridis, M.I., Neel, B.G. Stops along the RAS pathway in human genetic disease. In: Nat Med. 2006 Mar;12(3):283-285. Nature;2006. p. 283-285.