Howard A. Young, Ph.D.

Howard A. Young, Ph.D.
Senior Investigator
Head, Cellular and Molecular Immunology Section

Howard Young has expertise in the regulation and characterization of cytokine gene expression with a special emphasis on interferons. The Young laboratory has as its major focus how disruption of the control of interferon-γ (IFN-γ) gene expression during development and maturation of the cellular immune system impacts the host inflammatory response and the development of autoimmune disease and cancer. His laboratory has developed a mouse model of chronic Interferon-gamma expression that results in 3 different autoimmune diseases resembling lupus, aplastic anemia and primary biliary cirrhosis. This model may provide new insight into the initiation and progression of these diseases.

Areas of Expertise
1) interferon biology 2) cytokine gene expression 3) interferon-gamma 4) autoimmunity 5) innate immunity

Contact Info

Howard A. Young, Ph.D.
Center for Cancer Research
National Cancer Institute
Building 560, Room 31-23 (Office)
Frederick, MD 21702-1201
Ph: 301-846-5743/5700
younghow@mail.nih.gov

The laboratory studies the control of gene expression during the development and maturation of the cellular immune system in mediating antitumor and anti-inflammatory immune responses. The general goals are to use cellular and molecular approaches to investigate the consequences of persistent exposure to interferon-γ (IFN-γ) and how it alters host physiology. To approach this question, we have generated a novel mouse model where a portion of the 3' untranslated region of the mRNA has been changed, resulting in a much more stable mRNA and this will now permit us to understand the consequences of persistent IFN-γ expression on the host. We have backcrossed this change onto the murine C57BL/6 and Balb/c genetic backgrounds and as a consequence have developed new mouse models for lupus, primary biliary cholangitis and aplastic anemia. These mice are characterized by low but chronic IFN-γ expression. As a result there is persistent upregulation of IFN-γ inducible genes, resulting in the development of autoimmunity. Overall, our studies represent a cellular and molecular analysis of the consequences of aberrant regulation of cytokine gene expression in lymphoid cells and the effects on the host physiology and immune system development and function. Our studies provide a basis for developing a more complete understanding of the effects of IFN-γ expression during the pathogenesis of autoimmune diseases, cancer and infection.

Our collaborators include NCI investigators Giorgio Trinchieri, Dan McVicar, Dennis Klinman, and David Wink. In addition we have collaborations with Dr. Stefanie Vogel (University of Maryland School of Medicine), Dr. Dan Barber (NIAID), Dr. Bira Arya (NIA), Dr. Monika Wolters (The Netherlands) and Dr. Richard Siegel (NIAMS).

 

Scientific Focus Areas:
Cancer Biology, Cell Biology, Immunology, Molecular Biology and Biochemistry, Systems Biology
  1. Lin FC, Karwan M, Saleh B, Hodge DL, Chan T, Boelte KC, Keller JR, Young HA.
    Blood. 53: 33-45, 2014. [ Journal Article ]
  2. Hodge DL, Berthet C, Coppola V, Kastenmüller W, Buschman MD, Schaughency PM, Shirota H, Scarzello AJ, Subleski JJ, Anver MR, Ortaldo JR, Lin F, Reynolds DA, Sanford ME, Kaldis P, Tessarollo L, Klinman DM, Young HA
    J. Autoimmunity. 53: 33-45, 2014. [ Journal Article ]
  3. McFarland AP, Savan R, Wagage S, Addison A, Ramakrishnan K, Karwan M, Duong T, Young HA.
    PLoS ONE. 6: e16967, 2011. [ Journal Article ]
  4. McLean MH, Dieguez D Jr, Miller LM, Young HA
    Gut. 64: 332-341, 2015. [ Journal Article ]
  5. Savan R, McFarland AP, Reynolds DA, Feigenbaum L, Ramakrishnan K, Karwan M, Shirota H, Klinman DM, Dunleavy K, Pittaluga S, Anderson SK, Donnelly RP, Wilson WH, Young HA.
    Blood. 117: 575-84, 2011. [ Journal Article ]

Dr. Howard Young obtained his Ph.D. in microbiology at the University of Washington and carried out postdoctoral research at the NCI under Drs. Edward Scolnick and Wade Parks. He was a member of the Laboratory of Molecular Immunoregulation at NCI from 1983 to 1989 prior to joining the Laboratory of Experimental Immunology in 1989. He was President of the International Society for Interferon and Cytokine Research (2004-2005) and served as Chair of the Immunology Division of the American Society for Microbiology. He has also served as Chair of the NIH Cytokine Interest Group and Co-Chair of the NIH Immunology Interest Group. He is a two-time recipient of the NIH Director's Award for Mentoring (2000, 2006) and in 2006 he received the National Public Service Award. In 2007 he was named Deputy Chief of the Laboratory of Experimental Immunology.

Name Position
Kevin Chen Postbaccalaureate Fellow
Nkolika Egbukichi Ph.D. Postdoctoral Fellow (CRTA)
Rebecca Erwin-Cohen Ph.D. Postdoctoral Fellow (CRTA)
John Fenimore Postbaccalaureate Fellow
Megan M. Hess Postbaccalaureate Fellow (CRTA)
Tomoaki Hoshino M.D., Ph.D. Research Collaborator
Michael Sanford Research Biologist
Julio C. Valencia, M.D. Staff Scientist