David M. Rothstein, M.D.

David M. Rothstein, M.D.

Contact

Campus: Biomedical Science Tower, 203 Lothrop St

Office: W1545

Pittsburgh, PA 15213

Ph: 412-383-6960

Fax: 412-624-1172

rothsteind@upmc.edu

Website »

Education

  • B.A., University at Buffalo
  • M.D., The University of Pennsylvania School of Medicine (1980)
  • Postdoc, Hospital of the University of Pennsylvania, Internal Medicine; Brigham and Womens Hospital, Nephrology; Dana Farber Cancer Institute, Immunology Research

Academic Affiliation

  • Professor, Pittsburgh Steelers Chair in Transplantation
  • Professor, Department of Surgery
  • Professor, Department of Medicine
  • Professor, Department of Immunology

About Research

The Rothstein lab is focused on immunoregulation mediated by the balance between regulatory (Bregs) and inflammatory/effector (Beff) B cells. We identified TIM-1, a molecule key to Breg development and expression of a variety of anti-inflammatory and coinhibitory molecules utilized by Bregs to suppress immune responses. Specific deletion of TIM-1 expression on B cells results in spontaneous autoimmunity. We are now re-examining the role of plasma cells as regulatory B cells; identifying factors that control Breg expansion, examining localization of Breg function, and trying to determine whether Bregs arise stochastically or as a lineage.  In contrast, we have identified TIM-4 as a marker for iBeffs that strongly promote inflammation through expression of a host of inflammtory cytokines. We are curently comparing the gene expression profiles and examining the epigenetic regulation of TIM-1 versus TIM-4+ B cells. Thus, we are engaged in novel studies to expand our understanding of the biology of these potent immune regulators in murine autoimmune and allograft models. We also perform translational studies examining the ratio of Bregs/Beff cells (through their relative expression of IL-10 vs. TNFalpha) in the peripheral blood of transplant patients. This ratio serves as an indicator of immunological reactivity and serves as an accurate early prognostic marker for renal allograft outcomes. Ultimately, this biomarker may allow us to indivudalize immunosuppressive therapy in  transplant patients.

Selected Publications

1. Ding Q, Yueng M, Camirand G, Zeng Q, Akiba H, Yagita H, Chalasani G, Sayegh MH, Najafian N, and Rothstein DM. Regulatory B cells are identified by TIM-1 and can be induced through TIM-1 ligation to promote tolerance in mice. J Clin Invest. 2011. 121:3645-56. PMCID: PMC316395

2. Mohib K, Cherukuri A, Zhou Y, Watkins, S. and Rothstein DM. Antigen-dependent interactions between regulatory B cells and T cells at the T:B border inhibit subsequent T cell interactions with DCs. 2020. Am J Transplant. 2020. (1):52-63. PMID: 31355483

3. Zhixing S , Yuan W, Kuchroo VK, Mohib K, Rothstein DM. B cell derived IL-4 promotes IL-10+ regulatory B cells and Th2 T cell responses in vivo. In Press. Frontiers Immunol.

4. Cherukuri A, Salama A, Mehta R, Mohib K, Zheng L, Magee C, Harbar M, Stauss H, Baker RJ, Tevar A, Landsittel D, Lakkis FG, Hariharan S, and Rothstein DM.   Transitional B Cell Cytokines as a Predictive Biomarker in Renal Transplantation.  Science Translational Medicine.  2021 13(582):eabe4929. PMID: 33627487

5. Cherukuri A, Mohib K, and Rothstein, DM. Regulatory B cells: TIM-1, Transplant Tolerance, and Rejection.Immunological Reviews. 2021. 299:31-44. doi: 10.1111/imr.12933.

Complete list of publications

Research Interests

  • Immunoregulation/Immunological Tolerance
  • Adaptive Immunity Transplantation
  • Human Immunology
  • Innate Immunity

Lab Information