Dr. Center is Boston University’s Associate Provost for Translational Research and the Director of the Clinical and Translational Research Institute funded by the NIH. He directs Boston University’s efforts to facilitate translational research and advance team science, with a focus on the use of innovative methods for drug and device discovery and delivery and developing creative tools to expedite and retool traditional research processes.
His own laboratory is interested in two major themes which revolve around roles for Interleukin-16, co-discovered with Bill Cruikshank in 1982. The first theme relates to the functions of IL-16 as a immunomodulatory cytokine. Over the past several years, in collaboration with Bill Cruikshank, he has studied the role of IL-16 in recruitment and development of Regulatory T cells and demonstrated that it plays a key role in tolerance to airborne allergens. Utilizing transgenic knockout and overexpressing mice his laboratory is involved in demonstrating the patterns of CD4+ T cell trafficking through lymph nodes and lung parenchymal in normal and immunologically challenged lungs and identifying potential therapeutic implications of altering recruitment patterns of Regulatory T cells.
The second major emphasis of his laboratory relates to the functional properties of the precursor protein for IL-16, Pro-IL-16 as a tumor suppressor gene. In these studies, along with Yujun Zhang he has shown that Interleukin-16 is synthesized as a precursor which is present in cytoplasm and nucleus of resting T cells. It contains a phosphorylation regulated nuclear localization motif and binds a nuclear chaperone hsc70 which is essential for transport to the nucleus where its presence induces arrest of the cell cycle at G0/G1. It inhibits the cell cycle by acting as a scaffolding protein that assembles a histone deacetylase complex targeted via binding to GA-BP to the Skp2 promoter using intermolecular PDZ binding motifs. Skp2 is an essential member of the ubiquitin ligase protein degradation pathway responsive for degrading the cell cycle cyclin dependent kinase inhibitor p27. In the presence of pro-IL-16, the complex inhibits Skp2 transcription, which in turn decreases p27 degradation resulting in rises in p27 levels and arrest of the cell cycle in G1. Current studies are directed at identifying mutations in Pro-IL-16 that predispose to T cell malignancies and determining its role is permissive exit from G1 in normal T cell activation and proliferation following antigen stimulation.
- Gordon and Ruth Snider Chair, Pulmonary, Allergy, Sleep & Critical Care Medicine, Medicine, Boston University School of Medicine
- Gordon and Ruth Snider Professor of Pulmonary Medicine, Pulmonary, Allergy, Sleep & Critical Care Medicine, Medicine, Boston University School of Medicine
- Professor, Pulmonary, Allergy, Sleep & Critical Care Medicine, Medicine, Boston University School of Medicine
- Research Professor, Biochemistry, Boston University School of Medicine
- Section Chief, Pulmonary, Allergy, Sleep & Critical Care Medicine, Medicine, Boston University School of Medicine
- Mentor for Graduate Medical Students, Boston University School of Medicine, Division of Graduate Medical Sciences
- Boston University School of Medicine, MD
- Boston University, BA
- Published on 10/1/2017
Ravid K, Seta F, Center D, Waters G, Coleman D. Catalyzing Interdisciplinary Research and Training: Initial Outcomes and Evolution of the Affinity Research Collaboratives Model. Acad Med. 2017 Oct; 92(10):1399-1405. PMID: 28445220.
- Published on 11/3/2014
Curiel-Lewandrowski C, Yamasaki H, Si CP, Jin X, Zhang Y, Richmond J, Tuzova M, Wilson K, Sullivan B, Jones D, Ryzhenko N, Little F, Kupper TS, Center DM, Cruikshank WW. Retraction: Loss of nuclear pro-IL-16 facilitates cell cycle progression in human cutaneous T cell lymphoma. J Clin Invest. 2014 Nov; 124(11):5085. PMID: 25365075.
- Published on 2/1/2014
Richmond J, Tuzova M, Cruikshank W, Center D. Regulation of cellular processes by interleukin-16 in homeostasis and cancer. J Cell Physiol. 2014 Feb; 229(2):139-47. PMID: 23893766.
- Published on 5/31/2012
Center DM, Schwartz DA, Solway J, Gail D, Laposky AD, Lin QS, Gan W. Genomic medicine and lung diseases. Am J Respir Crit Care Med. 2012 Aug 1; 186(3):280-5. PMID: 22652029.
- Published on 3/27/2012
Shamoon H, Center D, Davis P, Tuchman M, Ginsberg H, Califf R, Stephens D, Mellman T, Verbalis J, Nadler L, Shekhar A, Ford D, Rizza R, Shaker R, Brady K, Murphy B, Cronstein B, Hochman J, Greenland P, Orwoll E, Sinoway L, Greenberg H, Jackson R, Coller B, Topol E, Guay-Woodford L, Runge M, Clark R, McClain D, Selker H, Lowery C, Dubinett S, Berglund L, Cooper D, Firestein G, Johnston SC, Solway J, Heubi J, Sokol R, Nelson D, Tobacman L, Rosenthal G, Aaronson L, Barohn R, Kern P, Sullivan J, Shanley T, Blazar B, Larson R, FitzGerald G, Reis S, Pearson T, Buchanan T, McPherson D, Brasier A, Toto R, Disis M, Drezner M, Bernard G, Clore J, Evanoff B, Imperato-McGinley J, Sherwin R, Pulley J. Preparedness of the CTSA's structural and scientific assets to support the mission of the National Center for Advancing Translational Sciences (NCATS). Clin Transl Sci. 2012 Apr; 5(2):121-9. PMID: 22507116.
- Published on 11/14/2011
Curiel-Lewandrowski C, Yamasaki H, Si CP, Jin X, Zhang Y, Richmond J, Tuzova M, Wilson K, Sullivan B, Jones D, Ryzhenko N, Little F, Kupper TS, Center DM, Cruikshank WW. Loss of nuclear pro-IL-16 facilitates cell cycle progression in human cutaneous T cell lymphoma. J Clin Invest. 2011 Dec; 121(12):4838-49. PMID: 22080865.
- Published on 11/9/2011
Granada M, Wilk JB, Tuzova M, Strachan DP, Weidinger S, Albrecht E, Gieger C, Heinrich J, Himes BE, Hunninghake GM, Celedón JC, Weiss ST, Cruikshank WW, Farrer LA, Center DM, O'Connor GT. A genome-wide association study of plasma total IgE concentrations in the Framingham Heart Study. J Allergy Clin Immunol. 2012 Mar; 129(3):840-845.e21. PMID: 22075330.
- Published on 12/1/2010
Bauchner H, Felson D, Center D. Creating a K-community of investigators. Acad Med. 2010 Dec; 85(12):1814. PMID: 21107029.
- Published on 3/18/2009
Green DS, Center DM, Cruikshank WW. Human immunodeficiency virus type 1 gp120 reprogramming of CD4+ T-cell migration provides a mechanism for lymphadenopathy. J Virol. 2009 Jun; 83(11):5765-72. PMID: 19297493.
- Published on 1/1/2008
Zhang Y, Tuzova M, Xiao ZX, Cruikshank WW, Center DM. Pro-IL-16 recruits histone deacetylase 3 to the Skp2 core promoter through interaction with transcription factor GABP. J Immunol. 2008 Jan 1; 180(1):402-8. PMID: 18097041.
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