- ASSOCIATE PROFESSOR Medicine, Clinical Immunology
Konstantina Alexandropoulos, PhD, is the Director of the T-cell Mediated Autoimmunity and Inflammation Laboratory. The laboratory focuses on elucidating several aspects of T cell physiology including T cell development, activation and trafficking under physiologic and disease conditions.
One major focus of our research is directed towards understanding the processes that cause aberrant T cell function and T cell-mediated autoimmune diseases exemplified by conditions such as rheumatoid arthritis, inflammatory bowel disease and diabetes. Under normal conditions, developing T cells in the thymus are educated not to attack the body's own tissues in a process known as T cell tolerance. T cell tolerance is exerted through two different mechanisms: a) elimination of mature, self-reactive T cells in the thymus (central tolerance); b) intrathymic generation of regulatory T cells which in peripheral tissues suppress the activity of self-reactive T cells that escape destruction in the thymus (peripheral tolerance). Establishment of both central and peripheral tolerance occurs in the thymus and is highly dependent on reciprocal interactions between developing T cells and the thymic epithelium, specifically medullary thymic epithelial cells (mTECs). Disruption of these interactions leads to aberrant elimination of autoreactive T cell clones, defective peripheral tolerance and autoimmunity, manifested as T cell-containing inflammatory infiltrates in and autoantibody production against peripheral tissues. We are currently using different mouse models with mutations that disrupt the development of mTECs to understand how disruption of thymic cross-talk between the medullary epithelium and T cells affects T cell development and autoimmunity.
Another area of research in the laboratory concentrates on elucidating the cellular and molecular mechanisms that regulate T cell activation and migration during the initiation and establishment of an immune response respectively. In these studies we are using knockout mice lacking expression of novel signaling proteins we previously characterized to study how these proteins regulate T cell activation, migration, and T cell-mediated immune responses under normal or inflammatory conditions. Our studies using mouse models coupled with molecular and biochemical approaches serve as a platform towards elucidating basic aspects of T cell physiology and are aimed towards identifying novel therapeutic targets to control the behavior of T cells in inflammation and autoimmunity.
Danzi N, Donlin L, Alexandropoulos K. Regulation of Medullary Thymic Epithelial Cell Differentiation and Function by the Signaling Protein Sin . J. Exp. Med. 2010; 207(5): 999-1013.
Alexandropoulos K, Regelmann A. Chat-H/CasL: A novel adapter complex that regulates T lymphocyte physiology. Imm. Rev. 2009; 232(1): 160-174.
Regelmann AG, Danzl NM, Wanjalla C, Alexandropoulos K. The hematopoietic isoform of Cas-Hef-1-associated signal transducer regulates chemokine-induced inside-out signaling and T cell trafficking. Immunity 2006; 25: 907-918.
Natarajan M, Stewart JE Jr., Golemis E, Pugacheva E, Alexandropoulos K, Grammer JR, Gladson CL. HEF1 is a necessary and specific downstream effector of FAK that promotes the migration of glioblastoma cells. Oncogene 2006; 25: 1721-1732.
Donlin LT, Danzl N, Wanjalla C, Alexandropoulos K. Deficiency in Expression of the Signaling Protein Sin/Efs Leads to T lymphocyte Activation and Mucosal Inflammation. Mol. Cell. Biol 2005; 25: 11035-11046.
Xing L, Donlin LT, Miller RH, Alexandropoulos K. The Adapter Molecule Sin Regulates T-Cell-Receptor-Mediated Signal Transduction by Modulating Signaling Substrate Availability. Mol. Cell. Biol 2004; 24: 4581-4592.
Alexandropoulos K, Donlin LT, Xing L, Regelmann AG. Sin: Good or Bad? A T- lymphocyte perspective . Immonol. Rev 2003; 192: 181-195.
Donlin LT, Roman CA, Adlam M, Regelmann AG, Alexandropoulos K. Defective thymocyte maturation by transgenic expression of a truncated form of the adapter molecule and Fyn substrate, Sin. J. Immunol 2002; 169: 6900-6909.
Xing L, Ge C, Zeltser R, Maskevitch GR, Mayer BJ, Alexandropoulos K. c-Src signaling induced by the adapters Sin and Cas is mediated by the Rap1 GTPase. Mol. Cell. Biol 2000; 20: 7363-7377.
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.
Dr. Alexandropoulos has not yet completed reporting of Industry relationships.
Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.
Icahn Medical Institute
1425 Madison Avenue, 11th Floor, Rm 11-23C
New York, NY 10029