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.
- Assistant Professor, Microbiology, Boston University School of Medicine
- Center Faculty Member, Arthritis Center, Boston University School of Medicine
- Graduate Faculty (Primary Mentor of Grad Students), Boston University School of Medicine, Division of Graduate Medical Sciences
- Universiteit Gent, PhD
- Universiteit Gent, MSc
- Published on 3/7/2018
Fleury M, Belkina AC, Proctor EA, Zammitti C, Simms RW, Lauffenburger DA, Snyder-Cappione JE, Lafyatis R, Dooms H. Increased Expression and Modulated Regulatory Activity of Coinhibitory Receptors PD-1, TIGIT, and TIM-3 in Lymphocytes From Patients With Systemic Sclerosis. Arthritis Rheumatol. 2018 Apr; 70(4):566-577. PMID: 29245183.
- Published on 12/4/2017
Jones Iv AR, Coleman EL, Husni NR, Deeney JT, Raval F, Steenkamp D, Dooms H, Nikolajczyk BS, Corkey BE. Type 1 diabetes alters lipid handling and metabolism in human fibroblasts and peripheral blood mononuclear cells. PLoS One. 2017; 12(12):e0188474. PMID: 29206239.
- Published on 5/17/2017
Smith NM, Wasserman GA, Coleman FT, Hilliard KL, Yamamoto K, Lipsitz E, Malley R, Dooms H, Jones MR, Quinton LJ, Mizgerd JP. Regionally compartmentalized resident memory T cells mediate naturally acquired protection against pneumococcal pneumonia. Mucosal Immunol. 2018 Jan; 11(1):220-235. PMID: 28513594.
- Published on 3/29/2017
Vazquez-Mateo C, Collins J, Fleury M, Dooms H. Broad induction of immunoregulatory mechanisms after a short course of anti-IL-7Ra antibodies in NOD mice. BMC Immunol. 2017 Mar 29; 18(1):18. PMID: 28356069.
- Published on 2/8/2017
Nicholas D, Proctor EA, Raval FM, Ip BC, Habib C, Ritou E, Grammatopoulos TN, Steenkamp D, Dooms H, Apovian CM, Lauffenburger DA, Nikolajczyk BS. Advances in the quantification of mitochondrial function in primary human immune cells through extracellular flux analysis. PLoS One. 2017; 12(2):e0170975. PMID: 28178278.
- Published on 7/4/2013
Dooms H. Interleukin-7: Fuel for the autoimmune attack. J Autoimmun. 2013 Sep; 45:40-8. PMID: 23831438.
- Published on 11/16/2012
Schoenbrunn A, Frentsch M, Kohler S, Keye J, Dooms H, Moewes B, Dong J, Loddenkemper C, Sieper J, Wu P, Romagnani C, Matzmohr N, Thiel A. A converse 4-1BB and CD40 ligand expression pattern delineates activated regulatory T cells (Treg) and conventional T cells enabling direct isolation of alloantigen-reactive natural Foxp3+ Treg. J Immunol. 2012 Dec 15; 189(12):5985-94. PMID: 23162126.
- Published on 9/20/2012
Van Belle TL, Dooms H, Boonefaes T, Wei XQ, Leclercq G, Grooten J. IL-15 augments TCR-induced CD4+ T cell expansion in vitro by inhibiting the suppressive function of CD25 High CD4+ T cells. PLoS One. 2012; 7(9):e45299. PMID: 23028916.
- Published on 6/25/2012
Penaranda C, Kuswanto W, Hofmann J, Kenefeck R, Narendran P, Walker LS, Bluestone JA, Abbas AK, Dooms H. IL-7 receptor blockade reverses autoimmune diabetes by promoting inhibition of effector/memory T cells. Proc Natl Acad Sci U S A. 2012 Jul 31; 109(31):12668-73. PMID: 22733744.
- Published on 7/31/2011
Katzman SD, Hoyer KK, Dooms H, Gratz IK, Rosenblum MD, Paw JS, Isakson SH, Abbas AK. Opposing functions of IL-2 and IL-7 in the regulation of immune responses. Cytokine. 2011 Oct; 56(1):116-21. PMID: 21807532.
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