Damian  Kovalovsky, Ph.D.
Damian Kovalovsky, Ph.D.
Investigator

Center for Cancer Research
National Cancer Institute

Building 10 - Magnuson CC, Room 4B36
Bethesda, MD 20892
301-435-6451

Dr. Kovalovsky investigates the molecular mechanisms that control T-cell development, focusing on the development of innate-like lymphocytes. He has identified that the transcription factor PLZF confers the innate-like phenotype to iNKT cells and He is currently studying the role of PLZF and related transcription factors to the development of other innate-like lymphocytes.

Areas of Expertise
1) T-cell development 2) Innate-like lymphocytes 3) PLZF 4) gammadeltaT-cells 5) NKT 6) Transcription Factors

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.

Scientific Focus Areas:
Cell Biology, Immunology, Molecular Biology and Biochemistry
Selected Recent Publications
  1. Kovalovsky D, Pezzano M, Ortiz BD, Sant'Angelo DB.
    PLoS ONE. 5: e8675, 2010. [ Journal Article ]
  2. Knirr S, Gomos-Klein J, Andino BE, Harrow F, Erhard KF, Kovalovsky D, Sant'Angelo DB, Ortiz BD.
    PLoS ONE. 5: e15527, 2010. [ Journal Article ]
  3. Kovalovsky D, Alonzo ES, Uche OU, Eidson M, Nichols KE, Sant'Angelo DB.
    J. Immunol. 184: 6746-55, 2010. [ Journal Article ]
  4. Kovalovsky D, Yu Y, Dose M, Emmanouilidou A, Konstantinou T, Germar K, Aghajani K, Guo Z, Mandal M, Gounari F.
    J. Immunol. 183: 3873-84, 2009. [ Journal Article ]
  5. Papapetrou EP, Kovalovsky D, Beloeil L, Sant'angelo D, Sadelain M.
    J. Clin. Invest. 119: 157-68, 2009. [ Journal Article ]

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.

Name Position
Xin Cao Ph.D. Postdoctoral Fellow (Visiting)
Ying Lu Ph.D. Postdoctoral Fellow (Visiting)
Jun-Seock Son Ph.D. Postdoctoral Fellow (Visiting)
Xianyu Zhang Research Biologist

Summary

Dr. Kovalovsky investigates the molecular mechanisms that control T-cell development, focusing on the development of innate-like lymphocytes. He has identified that the transcription factor PLZF confers the innate-like phenotype to iNKT cells and He is currently studying the role of PLZF and related transcription factors to the development of other innate-like lymphocytes.

Areas of Expertise
1) T-cell development 2) Innate-like lymphocytes 3) PLZF 4) gammadeltaT-cells 5) NKT 6) Transcription Factors

Research

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.

Scientific Focus Areas:
Cell Biology, Immunology, Molecular Biology and Biochemistry

Publications

Selected Recent Publications
  1. Kovalovsky D, Pezzano M, Ortiz BD, Sant'Angelo DB.
    PLoS ONE. 5: e8675, 2010. [ Journal Article ]
  2. Knirr S, Gomos-Klein J, Andino BE, Harrow F, Erhard KF, Kovalovsky D, Sant'Angelo DB, Ortiz BD.
    PLoS ONE. 5: e15527, 2010. [ Journal Article ]
  3. Kovalovsky D, Alonzo ES, Uche OU, Eidson M, Nichols KE, Sant'Angelo DB.
    J. Immunol. 184: 6746-55, 2010. [ Journal Article ]
  4. Kovalovsky D, Yu Y, Dose M, Emmanouilidou A, Konstantinou T, Germar K, Aghajani K, Guo Z, Mandal M, Gounari F.
    J. Immunol. 183: 3873-84, 2009. [ Journal Article ]
  5. Papapetrou EP, Kovalovsky D, Beloeil L, Sant'angelo D, Sadelain M.
    J. Clin. Invest. 119: 157-68, 2009. [ Journal Article ]

Biography

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.

Team

Name Position
Xin Cao Ph.D. Postdoctoral Fellow (Visiting)
Ying Lu Ph.D. Postdoctoral Fellow (Visiting)
Jun-Seock Son Ph.D. Postdoctoral Fellow (Visiting)
Xianyu Zhang Research Biologist