Our Science – Kovalovsky Website
Damian Kovalovsky, Ph.D.
Dr. Kovalovsky received his Ph.D from the University of Buenos Aires, Argentina. He obtained postdoctoral training at the Molecular Oncology Research Institute, TUFTS-NEMC and at Memorial Sloan Kettering Cancer Center, where he studied the mechanisms of negative selection of thymocytes as well as the innate-like differentiation of iNKT cells.
Naive T-cells leave the thymus expressing unique T-cell receptors (TCR) that preferentially recognize foreign antigens. Activation by antigens triggers a proliferation and differentiation response in which only a small subset of T-cells acquire effector and memory functions. The requirement of this extrathymic differentiation step is what allows the system to learn from previous encounters and to adapt to respond to new antigens.
Innate-like T-cells, as invariant natural killer T-cells (iNKT), mucosal associated invariant T-cells (MAIT) and subsets of gdT-cells also express TCRs but with restricted variability. Contrarily to conventional T-cells, these cells leave the thymus with already acquired effector functions. This allows them to migrate to non-lymphoid tissues and to respond rapidly to stimulation. What controls the innate-like differentiation of T-cells during development is not completely known. In the case of iNKT and gdNKT cells it has been associated with specific co-stimulation during selection and the expression of the transcription factor PLZF, which is necessary for their innate-like phenotype. We are interested in understanding the mechanisms by which PLZF controls these phenotypes.
Epigenetics are the study of heritable changes in gene expression, which determines the transcriptional program during differentiation. Their analysis requires large numbers of cells which precludes its use in subpopulations with low cell numbers as innate-like lymphocytes. In order to better understand the molecular mechanisms that govern differentiation of these subtypes of lymphocytes we are working on modifications of current techniques to allow its applicability using small numbers of cells.
This page was last updated on 12/5/2013.