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Stephen Desiderio, M.D., Ph.D.

Stephen Vincent Desiderio, M.D., Ph.D.

Photo of Dr. Stephen Desiderio, M.D., Ph.D.

Director, Institute for Basic Biomedical Sciences

Professor of Molecular Biology and Genetics

Research Interests: Genomic plasticity; DNA recombination; immune development; lymphoid malignancies

Background

Dr. Stephen Desiderio is a professor of molecular biology and genetics at the Johns Hopkins University School of Medicine. His research focuses on the molecular and genetic mechanisms underlying immune system development. Dr. Desiderio serves as the director of the Institute for Basic Biomedical Sciences and director of the immunobiology program at the Institute of Cell Engineering (ICE).

Dr. Desiderio’s research team has made numerous contributions to our understanding of how immunity develops in health and disease. Their studies have shed light on the relationship between genetic rearrangement—the process by which immune diversity is generated—and the development of leukemia. They have discovered key elements of the triggers that turn on immune responses, and most recently have focused on the signals that instruct stem cells to become cells of the immune system.

Dr. Desiderio received his undergraduate degree in biology and Russian from Haverford College. He earned his Ph.D. and M.D. from the Johns Hopkins University School of Medicine. He completed a postdoctoral fellowship at the Massachusetts Institute of Technology. Dr. Desiderio joined the Johns Hopkins faculty in 1984.

From 1984 to 2004, Dr. Desiderio was an investigator of the Howard Hughes Medical Institute. From 1992 to 1999, he was director of the M.D.-Ph.D. program at the Johns Hopkins School of Medicine.

Dr. Desiderio is a member of several professional societies and has been honored by election to the Association of American Physicians and the American Society for Clinical Investigation.  He serves on the editorial board of the Journal of Molecular Medicine. In 2007, the governor appointed him to the Maryland Life Sciences Advisory Board. 

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Titles

  • Director, Institute for Basic Biomedical Sciences
  • Director, Immunobiology Program, Institute for Cell Engineering
  • Professor of Molecular Biology and Genetics
  • Professor of Medicine

Education

Degrees

  • M.D., Johns Hopkins University School of Medicine (Maryland) (1981)
  • Ph.D., Johns Hopkins University School of Medicine (Maryland) (1981)

Additional Training

  • B.A., Haverford College, Haverford, PA, 1974, Biology and Russian
  • Fellowship, Massachusetts Institute of Technology, Cambridge, MA, 1984

Research & Publications

Research Summary

Dr. Desiderio's research focuses on the molecular and genetic mechanisms responsible for development of the immune system. His research has shed light on how the immune system is able to respond to a spectacularly diverse set of invaders. His team’s studies have helped explain the relationship between genetic rearrangement—the process by which immune diversity is generated—and the development of leukemia.

The team has also discovered key elements of the triggers that turn on immune responses, and most recently has turned its attention to signals that instruct stem cells to become cells of the immune system.

Lab

The Desiderio lab is interested in the molecular and genetic mechanisms responsible for development of the immune system. Among the most spectacular examples of genomic plasticity are the processes that generate immunologic diversity, including V(D)J recombination. V(D)J recombination, which builds antigen receptor genes from discrete gene segments, shares mechanistic features with transposition and, as a potential source of DNA damage, is subject to tight control. One control mechanism, identified in this laboratory, restricts V(D)J recombination to a specific time in cell cycle through the periodic destruction of the V(D)J recombinase. Using a combination of genetics and biochemistry, our group has defined this process in detail. By constructing specific knock-in mutant mice, we have gone on to show that this mechanism protects against the development of lymphoid cancers and their associated chromosomal translocations. More recently, we have begun to study how V(D)J recombination is controlled at the level of chromatin modification, which may govern accessibility of particular loci to the recombinase.

A related interest is how immune cells respond to environmental cues. Activation of immune cells requires a balance between benefit and risk, and is tightly regulated. Some signals activate immune cells while others block responsiveness—a process called anergy. These signaling mechanisms share common features, including activation of kinases, mobilization of calcium and combinatorial regulation of transcription. We have recently uncovered a novel way in which calcium is regulated in response to antigen receptor stimulation and are now testing whether this mechanism contributes to the decision between activation and anergy.

Lab Website: Stephen Desiderio Laboratory

Selected Publications

View all on Pubmed

Yoo, J.-Y., Huso, D.L., Nathans, D. and Desiderio, S. (2002) Specific ablation of Stat3ß distorts the pattern of Stat3-responsive gene expression and impairs recovery from endotoxic shock. Cell 108:331-344.

Jiang, H., Chang, F.-C., Ross, A.E., Lee, J., Nakayama, K., Nakayama, K. and Desiderio, S. (2005) Ubiquitylation of RAG-2 by SKP2-SCF links destruction of the V(D)J recombinase to the cell cycle. Mol. Cell, 18(6): 699-709

Liu Y, Subrahmanyam R, Chakraborty T, Sen R, Desiderio S. (2007) A plant homeodomain in RAG-2 that binds hypermethylated lysine 4 of histone H3 is necessary for efficient antigen-receptor-gene rearrangement. Immunity 27:561-71.

Zhang, L., Reynolds, T.L., Shan, X. and Desiderio, S. (2011) Coupling of V(D)J recombination to the cell cycle suppresses genomic instability and lymphoid tumorigenesis. Immunity 34: 163-174.

Lu C., Ward A., Bettridge J., Liu Y., Desiderio S. (2015) An autoregulatory mechanism imposes allosteric control on the V(D)J recombinase by histone H3 methylation. Cell Rep. Jan 6;10(1):29-38

Academic Affiliations & Courses

Graduate Program Affiliation

Activities & Honors

Honors

  • Elected Member, American Society for Clinical Investigation, 1996
  • Elected Member, Association of American Physicians, 2013
  • Fellow, Jane Coffin Childs Memorial Fund for Medical Research, 1981 - 1984
  • Elected Member, The Henry Kunkel Society, 1999
  • Professors' Award for Excellence in Teaching, The Johns Hopkins University School of Medicine, 1993
  • Michael A. Shanoff Research Award, The Johns Hopkins University School of Medicine, 1980
  • Alpha Omega Alpha, 1981
  • Scholar of the Insurance Medical Scientist Scholarship Fund, 1979 - 1981
  • Phi Beta Kappa, 1973

Memberships

  • American Association for the Advancement of Science
  • American Society for Biochemistry and Molecular Biology
  • American Society for Clinical Investigation
  • Association of American Physicians
  • Clinical Immunology Society
  • Henry G. Kunkel Society

Professional Activities

  • Advisory Committee, Harvard Medical School, 2009
    Leder Human Biology Program
  • Board, European Genetics Foundation, 2007
  • Director, The Johns Hopkins University School of Medicine, 1992 - 1999
    M.D.-Ph.D. Program
  • Editorial Board, Journal of Molecular Medicine, 2007
  • Invited Participant, International Conference on Biosafety and Biosecurity, 2005
  • Invited Participant, Center for Civilian Biodefense Strategies and Defense Science Board, 2003
    Strategic Concepts for Biodefense
  • Life Sciences Advisory Board, State of Maryland, 2007
  • Organizer, Mid-Atlantic Immunobiology Conference, 1994
    Signal Transduction Session
  • Reviewer, National Institute on Aging, 2011
    Board of Scientific Counselors

Videos & Media

Stephen Desiderio - Johns Hopkins Institute for Basic Biomedical Sciences

Dr. Stephen Desiderio, director of the Johns Hopkins Institute for Basic Biomedical Sciences, talks about the center and what it has to offer for graduate education at Johns Hopkins in the basic sciences.

The Need for Funding Basic Research

Dr. Stephen Desiderio, director of Johns Hopkins Institute for Basic Biomedical Sciences, explains the current federal funding climate for biomedical research, the need for change and the dangers of not continuing to fund basic research. Dr. Desiderio's speech was recorded on October 29, 2013, at the Institute for Basic Biomedical Sciences' Molecules & Martinis event held in Philadelphia, Pennsylvania.

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