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

Center for Cancer Research
National Cancer Institute

Building 560, Room 31-23 (Office)
Frederick, MD 21702-1201
301-846-5743/5700

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. In addition, the laboratory is investigating a new cancer vaccine strategy utilizing tumor antigens engineered to adhere to the surface of probiotic microorganisms as a strategy to present these antigens to the gut and lung mucosal interfaces.

Areas of Expertise
1) interferon biology 2) cytokine gene expression 3) interferon-gamma 4) autoimmunity 5) innate immunity 6) probiotics

Regulation of Cytokine Gene Expression

The Cellular and Molecular Immunology Section 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 of this section are to use cellular and molecular approaches to investigate the consequences of persistent exposure to interferon-γ (IFN-γ) alters host physiology. The specific aim of the Cellular and Molecular Immunology Section is to study how chronic IFN-γ expression influences immune system development and maturation.

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 and this will now permit us to understand the role of this region on IFN-γ expression. We have backcrossed this genetic change onto the murine C57BL/6 and Balb/c genetic backgrounds and as a consequence have developed new mouse models for lupus and aplastic anemia. These mice are characterized by low but chronic IFN-γ expression. As a result there is persistent upregulation of IIFN-γ inducible genes, resulting in the development of autoimmunity. Overall, our studies represent a cellular and molecular analysis of the regulation of cytokine gene expression in lymphoid cells and the effects on the host. Our studies provide a basis for developing a more complete understanding of the effects of IFN-γ; expression during the pathogenesis of autoimmune disease, cancer and infection.

An additional project in the lab focuses on the introduction of target antigens coated onto probiotic bacteria, for the purpose of determining if intestinal mucosal exposure of these antigens can lead to a protective immune response. Preliminary results indicate that this approach can result in a systemic host immune response to a target antigen.

Our collaborators include NCI investigators Giorgio Trinchieri, Robert Wiltrout, 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. Khatijah Yusoff (Malaysia).

Scientific Focus Areas:
Cancer Biology, Cell Biology, Immunology, Molecular Biology and Biochemistry
Selected Key Publications
  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
Heekyong (Becky) Bae Ph.D. Postdoctoral Fellow (CRTA)
Alec Barlow Summer Student
Tomoaki Hoshino Guest Researcher
Della Reynolds Research Biologist
Michael Sanford Research Biologist
Julio C. Valencia M.D. Staff Scientist

Summary

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. In addition, the laboratory is investigating a new cancer vaccine strategy utilizing tumor antigens engineered to adhere to the surface of probiotic microorganisms as a strategy to present these antigens to the gut and lung mucosal interfaces.

Areas of Expertise
1) interferon biology 2) cytokine gene expression 3) interferon-gamma 4) autoimmunity 5) innate immunity 6) probiotics

Research

Regulation of Cytokine Gene Expression

The Cellular and Molecular Immunology Section 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 of this section are to use cellular and molecular approaches to investigate the consequences of persistent exposure to interferon-γ (IFN-γ) alters host physiology. The specific aim of the Cellular and Molecular Immunology Section is to study how chronic IFN-γ expression influences immune system development and maturation.

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 and this will now permit us to understand the role of this region on IFN-γ expression. We have backcrossed this genetic change onto the murine C57BL/6 and Balb/c genetic backgrounds and as a consequence have developed new mouse models for lupus and aplastic anemia. These mice are characterized by low but chronic IFN-γ expression. As a result there is persistent upregulation of IIFN-γ inducible genes, resulting in the development of autoimmunity. Overall, our studies represent a cellular and molecular analysis of the regulation of cytokine gene expression in lymphoid cells and the effects on the host. Our studies provide a basis for developing a more complete understanding of the effects of IFN-γ; expression during the pathogenesis of autoimmune disease, cancer and infection.

An additional project in the lab focuses on the introduction of target antigens coated onto probiotic bacteria, for the purpose of determining if intestinal mucosal exposure of these antigens can lead to a protective immune response. Preliminary results indicate that this approach can result in a systemic host immune response to a target antigen.

Our collaborators include NCI investigators Giorgio Trinchieri, Robert Wiltrout, 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. Khatijah Yusoff (Malaysia).

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

Publications

Selected Key Publications
  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 ]

Biography

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.

Team

Name Position
Heekyong (Becky) Bae Ph.D. Postdoctoral Fellow (CRTA)
Alec Barlow Summer Student
Tomoaki Hoshino Guest Researcher
Della Reynolds Research Biologist
Michael Sanford Research Biologist
Julio C. Valencia M.D. Staff Scientist