| University of Pittsburgh |  |
UPMC | |
Health Sciences @ Pitt | |
STI Clinical Website | |
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| Faculty | |
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David M. Rothstein
, M.D.
Professor 200 Lothrop Street Biomedical Science Tower, W1542 Pittsburgh, PA 15213 Phone: (412) 383-6960 Email: rothsteind@upmc.edu Faculty Research Interests Personal Web Page |
| Academic Affiliations | |
| Surgery, Medicine and Immunology | |
| Education | |
| 1980 -- MD The University of Pennsylvania School of Medicine, Philadelphia, PA 1980-1981 -- Internship in Internal Medicine Hospital of The University of Pennsylvania, Philadelphia PA 1982-1983 -- Residency in Internal Medicine Hospital of The University of Pennsylvania, Philadelphia PA 1984-1985 -- Renal Fellow (Clinical), Brigham and Women's Hospital, Boston MA 1985-1988 -- Renal Fellow (Research), Immunogenetics Laboratory at Brigham and Women's Hospital. Under direction of Dr. Charles B Carpenter, Professor of Medicine. 1988-8/92 -- Research Associate, Tumor Immunology Division, Dana-Farber Cancer Inst. Under the direction of Dr. Stuart Schlossman, Benacerraf Professor of Medicine |
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| Areas of Research Interest | |
| Basic Research, Translational Research, Tolerance Induction, Xenotransplantation, Cellular Transplantation, Immunotherapy, Immunologic Monitoring, Gene Therapy, T-cell Biology, Immune Regulation, Regulatory T-cells | |
| Research Interests | |
| My research interests are focused on several inter-related areas of transplantation and basic immunobiology: I. Role of CD45 in Tolerance and Immunity: CD45 is a transmembrane phosphatase that regulates T cell and B cell activation but plays a less well understood role in innate immune cells. mAbs targeting CD45 are potent induces of tolerance in murine models. CD45 ligation appears to induce tolerance through novel mechanisms that include induction of Tregs from non-Tregs, and regulation of Treg homeostasis. A role for B cells and T cell anergy remain poorly understood. We are studying various models that each elucidate different aspects of anti-CD45 mAb function Murine Models: islet cell transplantation, myoblast transplantation, autoimmunity (Diabetes and colitis). Non-human Primate models: anti-CD45RB is being examined in combination with anti-CD40 and sCD83, a novel agent that inhibits DC maturation. II. Induction of regulatory T cells and regulation of T cell homeostasis. Studies utilize Foxp3-reporter mice, retroviruses and other genetically altered mice to study the generation of Treg and regulation of their homeostatic proliferation. Similar tools are utilized to determine whether and how various experimental therapeutic agents augment generation of regulatory T cells. Studies of biochemical pathways involved, are in progress. III. The role of CD45 in innate immune activation. Studies reveal a unique role for CD45 in DC function. CD45-mutant mice are specifically unable to reject islet allografts due to a defect in alloactivation of the innate immune system IV. The role of TIM molecules in transplantation. TIM molecules are expressed by a small fraction of Th1 and Th2 –differentiated T cells. New data indicates that tolerogenic anti-TIM mAbs may actually target other components of the immune system to induce tolerance. These studies may indicate previously unrecognized regulatory roles and crosstalk between different types of immune cells. |
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| Publications | |
| 1. Fecteau, S, Basadonna, GP., Freitas, A., Ariyan, C., Sayegh, M., Rothstein, DM. CTLA-4 Upregulation Plays A Role In Tolerance Through CD45. Nature Immunology. 2001. 2: 58-63. 2. Sho M, Kishimoto K, Harada H, Livak M, Sanchez-Fueyo A, Yamada A, Zheng XX, Strom TB. Basadonna G, Sayegh MH and Rothstein DM. Requirements For Induction And Maintenance of Peripheral Tolerance In Stringent Allograft Models. 2005. Proc Natl Acad Sci USA. Track II. 102:13230-35. 3. Tang, AL., Teijaro, JR., Njau, MN., Chandran, SS., Azimzadeh, A., Nadler, SG., Rothstein DM., and Farber DL. CTLA-4 expression is an indicator and regulator of steady-state CD4+FoxP3+ T cells homeostasis. J Immunology. 2008. 181:1806-13. 4. Li. X, Rothstein, DM and Sayegh, MH. Costimulatory pathways in transplantation: challenges and new developments. Immunological Reviews. 2009 In Press. 5. Camirand G, Wang Y., Wan YY., Kai YJ., Guz, G., Deng S., Farber, D., Perkins, DL., Finn, PW., Lakkis, F., Shlomchik, WD, Flavell RA., and Rothstein, DM. CD45 Ligation Induces Foxp3+ Tregs Through de novo Conversion and Augmentation of Homeostatic Proliferation. Submitted. |
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| Memberships | |
| AST, ASN | |