Hans Dooms, Ph.D.

Assistant Professor of MedicineHans Dooms (2)

Ph.D.: Ghent University, Belgium

Postdoctoral: University of California, San Francisco

Keywords

T cells, autoimmunity, cytokines, immunologic memory, type 1 diabetes

Research

The broad goal of my research is to understand the role of T cells in the pathogenesis of autoimmune diseases and to apply this knowledge for the development of new therapeutic interventions. My laboratory uses in vivo models of autoimmune diseases to follow T cell responses against tissues (e.g. pancreatic islets) and to identify molecules (e.g. cytokines) that orchestrate the autoimmune attack. In addition, we are developing novel gene-deficient and transgenic models to obtain mechanistic insights into the cytokine signaling pathways and transcription factors that drive autoreactive T cells.

To combine the capacity for potent protective responses against pathogens with the prevention of autoimmunity and tissue damage, the immune system works with “checks and balances” to generate the appropriate cellular response to foreign antigens while maintaining tolerance to self. Autoimmune diseases result from breakdowns of these control mechanisms, either due to defects in tolerance-inducing pathways or because autoreactive lymphocytes acquire resistance to proper regulation. I am particularly interested in the contribution of one type of lymphocytes, memory T cells, to the autoimmune process. Memory T cells possess superior effector capacity and long-term viability to fulfill their physiologic function of protecting the host against recurring infections and tumors. However, memory T cells that develop against self-antigens are, precisely due to these characteristics, a significant clinical problem and a major obstacle to restoring tolerance for the therapy of autoimmune diseases and the protection of transplants.

We are currently studying type 1 diabetes as a model of autoimmunity. Islet-specific memory T cells are present in animal models as well as patients with type 1 diabetes and perpetuate anti-islet immune responses, ultimately leading to the onset of hyperglycemia. We recently found that blocking the cytokine Interleukin-7 (IL-7) inhibits these pathogenic memory cells and stops further destruction of the insulin-producing cells in the pancreas. Cytokines such as IL-7 and IL-2 are important regulators for the differentiation, programming and maintenance of memory T cells and modulating their function is a promising approach for controlling memory responses. Ongoing projects in the lab focus on (1) elucidating the molecular and cellular mechanisms underlying IL-7’s role in type 1 diabetes, (2) understanding the dual function of IL-2 in immunity and tolerance and (3) identifying transcriptional programs in CD4+ memory T cells.

 

Selected publications

  1. Penaranda, C., Kuswanto, W., Hofmann, J., Kenefeck, R., Narendran, P., Walker, L.S.K., Bluestone,    J.A.B., Abbas, A. K.A., and Dooms, H. “IL-7 receptor blockade reverses autoimmune diabetes by promoting inhibition of effector/memory T cells”  Proc. Natl. Acad. Sci. USA, 2012,109:12668-73
  2. Dooms, H. and Abbas, A. K. “Revisiting the role of IL-2 in autoimmunity” Eur. J. Immunol., 2010, 40:1538-1540
  3. Barron, L.*, Dooms, H.*, Hoyer, K., Kuswanto, W., Hofmann, J., O’Gorman, W., and Abbas, A., “Cutting Edge: Mechanisms of IL-2–dependent maintenance of functional regulatory T cells” J. Immunol., 2010, 185: 6426-6430; * both authors contributed equally to this work
  4. O’Gorman, W.*, Dooms, H.*, Thorne, S., Kuswanto, W., Simonds, E., Krutzik, P., Nolan, G., Abbas, A., “The initial phase of an immune response functions to activate regulatory T cells” J. Immunol., 2009, 183: 332-339; * both authors contributed equally to this work
  5. Dooms, H., Wolslegel, K., Lin, P., and Abbas, A. K., “Interleukin-2 enhances CD4+ T cell memory by  promoting the generation of IL-7Ra-expressing cells” J. Exp. Med., 2007, 204: 547-557
  6. Dooms, H. and Abbas, A.K., “Control of CD4+ T-cell memory by cytokines and costimulators” Immunol Rev., 2006, 211:23-38
  7. Dooms, H., Kahn, E., Knoechel, B., and Abbas, A. K., “Interleukin-2 induces a competitive survival advantage in T lymphocytes” J. Immunol., 2004, 172: 5973-5979

Primary teaching affiliate
of BU School of Medicine