Boston University Medical Campus
Pulmonary, Critical Care, and Allergy Medicine

Medical School: Boston University
Internship: University Hospital, Boston University
Residency: University Hospital, Boston University
Fellowship: Boston University, Pulmonary
Other Post-doctoral Fellowships/Training: Allergy and Immunology, Peter B. and Robert B. Brigham Hospitals, Harvard Medical School
Board Certifications: Internal Medicine, Pulmonary Medicine, Allergy and Immunology

Special Interests:
RESEARCH:

• Lymphocyte Migration
• Mechanisms of Inflammation
• Interleukin 16
• Asthma pathophysiology
• Translational Research.

CLINICAL:

• Immune based lung diseases

Laboratory Interests:
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. As a result he directs Boston University’s efforts to facilitate translational research in all venues and leads a major effort in identifying new areas of development.

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.

Links:

• Boston University Pulmonary Center: Immunology Group
• Boston University Asthma Clinical Center
• Boston University Allergy Clinical Center
• Boston University CTSI

Selected Publications:

1. Morgan, R, McAllister, B, Cross, L, Green, D, Kornfeld, H, Center, DM, and Cruikshank, WW. 2007 Histamine 4 receptor activation induces recruitment of FoxP3+ T cells and inhibits allergic asthma in a murine model. J. Immunol 178(12):8081-9.
2. McFadden, C, S, Green, D, Yamasaki, H, Center, DM, Cruikshank, WW. 2007 Preferential migration of T regulatory cells induced by IL-16. 2007. J. Immunol. 179: 6439-45.
3. Zhang, Y, Tuzova, M., Xiao, Z-XJ., Hanson, SK, Xie, H, Kornfeld, H, Cruikshank, WW, Center, DM. 2007 Pro-Interleukin-16 is a scaffold protein which targets Histone Deacetylase 3 to Transcription Factor GABP in the Skp2 Core Promoter. 2008 J. Immunol. 180:402-408.
4. Center, DM. 2007 Time to take the “Idio” out of Idiopathic Pulmonary Fibrosis: A call to arms. (Editorial). Am. J. Resp Crit Care Med 175(11):1101-2.

Selected Reprints:

• Pro-Interleukin-16 is a scaffold protein which targets Histone Deacetylase 3 to Transcription Factor GABP in the Skp2 Core Promoter

Dr. Center’s clinic is in the Doctor’s Office Building, 4th floor
617-638-7480