HBA Mentoring Program – Mentors

Profile and Research Interests: 

Dr. Kontaridis received her undergraduate degrees (B.A. and B.S.) from the University of Florida in Classics and Chemistry, and subsequently, obtained her master’s degrees both in Pharmacology and in 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 SHP2, in cell growth and skeletal muscle differentiation. Dr. Kontaridis’ interest in continuing to work on SHP2 phosphatase led her to accept a postdoctoral position with Dr. Benjamin Neel, at Beth Israel Deaconess Medical Center (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 2015, she was named the Interim Director of Basic Cardiovascular Research at BIDMC and in 2016 was promoted to Associate Professor of Medicine at Harvard Medical School.  In her research, Dr. Kontaridis has made multiple interesting observations about SHP2 and its role in cardiac pathophysiology and disease, as well as in autoimmunity. 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-R01s and NCATS-TRND) as well as has garnered support from industry and pharmaceutical companies (Novartis, GSK, Arqule).

Dr. Kontaridis is actively involved in the BIDMC/Cardiology Division and is also a member of the Cardiology Fellowship Selection Committee, serves as Chair for the Joint Commission for the Status of Women (JCSW) at Harvard Medical School, and is Chair 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.

Dr. Kontaridis’ research is focused on understanding the signaling pathways that mediate cellular and molecular pathogenesis of disease. The Kontaridis research program focuses on the fundamental mechanisms associated with aberrant protein tyrosine phosphatase signaling and how mutations in these enzymes lead to congenital heart disease and end-stage heart failure, as well as autoimmunity and cancer.  The 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 that cause disease and allow for an individualized approach to therapeutic targeting. Specifically, the lab is focused on four main interests:

1) Understanding the functional mechanisms associated with SHP2 activity in the development of Systemic Lupus Erythematosus (SLE).  The lab is interested in understanding how SHP2 is involved in mediating the onset/propagation of SLE.  The lab’s data indicate that SHP2 activity is increased in SLE and that this mediates proliferation of cytotoxic T cells, thereby causing lupus pathogenicity.  Use of a novel inhibitor for SHP2 ameliorated SLE pathogenesis; increased lifespan, decreased fibrosis and inflammation in tissues, and reduced the number of skin lesions in SLE-prone mice. These data suggest that development of an SHP2 inhibitor may serve as a novel treatment for SLE.

2) Elucidation of the cardiomyogenic and gastrointestinal defects associated with Noonan (NS) and LEOPARD (LS) Syndromes.  The lab is interested in investigating the cardiomyogenic and gastrointestinal defects associated with NS and LS, two autosomal dominant congenital RASopathy disorders principally caused by unique mutations in the protein tyrosine phosphatase SHP2.  The Kontaridis group was the first to generate a mammalian mouse model system to study LS.  Consequently, they identified that LS mutations led to increased AKT/mTOR activity.  Moreover, they identified that the cardiac hypertrophy associated with LS could be reversed with treatment of Rapamycin.  In addition, the lab is investigating how NS and LS mutations differentially affect multiple-specific tissue lineages during development in mouse embryos and in iPSCs.

3) Determining the phosphatase-independent functions of SHP2 in development and disease.  The Kontaridis lab identified novel functional roles for SHP2 in the regulation of downstream signaling events. They were the first to identify that LS-associated SHP2 mutations, unlike the NS mutations, were loss-of-function for phosphatase activity and behaved as dominant-negatives in downstream signaling.  This created a paradigm shift that altered the way phosphatases were thought to function in cellular signaling, in general, and suggested that RASopathy disorders should be distinguished by mutational analysis rather than by clinical presentation alone. Currently, the lab is investigating whether SHP2 has unique phosphatase-independent functions critical for the propagation of downstream signaling.

4) Deciphering the cardioprotective effects of the small G protein RhoA in the failing adult heart.  The Kontaridis lab has discovered that RhoA, an enzyme regulated in part by SHP2, is involved in transitioning compensatory cardiac hypertrophy to heart failure.  Moreover, it is involved in fibrosis, making RhoA and its downstream effectors attractive targets for therapeutic approaches in treating cardiac disease.  Projects in the lab are focused on elucidating the RhoA-mediated signaling pathways involved in fibrosis and in onset of end-stage heart failure.