Pittsburgh Surgical Outcomes Research Center
Transforming the conduct of clinical research

Diana M Metes, MD

  • Professor of Surgery and Immunology, Co-Director Human Immunology Program, Thomas E. Starzl Transplantation Institute, Director, Human Immunology Core Lab, Thomas E. Starzl Transplantation Institute

Education & Training

  • MD, Faculty of General Medicine, Institute of Medicine and Pharmacy
  • Residency, Institute of Hematology, Bucharest, Romania

Representative Publications

Research Interest Summary

Immune responses to EBV Memory T cell responses in solid organ transplant patients DC immunobiology in solid organ transplant recipients

Research Interests

Human immunology, transplantation, EBV, T cell memory, dendritic cells
Solid organ transplantation is the treatment choice for patients with end-stage organ failure diseases. While life-long immunosuppressive drugs are given to these patients to prevent allograft rejection and promote immune tolerance, these drugs trigger unwanted side effects, such as opportunistic infections and cancers, including EBV-driven PTLD. My lab’s research interests focus on three aspects of the immune response in transplant recipients, in the effort to identify specific markers or/and pathways that predict immune quiescence, rejection or the risk for EBV complications:

Immune responses to EBV: Immune monitor EBV-specific CD8+ T cells in solid organ TX patients. Analysis of EBV-specific CD8+ T cell regulation by chronic EBV-cognate antigen stimulation, inhibitory molecules and gc helper cytokines. Cellular and molecular assessment of T cell exhaustion vs effector T cell signatures.

Immune responses to alloantigens: Assess the role of Tregs and of memory T cells in triggering allo-immune quiescence vs allograft rejection. Investigate the impact of depleting vs non-depleting induction therapies on the phenotype and function of memory T cells in solid organ TX recipients.

DC immunobiology: study the role of pharmacologic agents in promoting DC tolerogenicity with implications for the regulation of recall- and allo-Ag specific T cell responses.

 

Do you currently have a research resident in your lab? Please add details

I do not have a resident in the lab. I do however have 2 visiting transplant nephrology fellows.

Have you previously mentored residents in research projects? Please add details

I have previously mentored residents and fellows (infection disease and transplant nephrology)

Project information:

Project type: translational research

Research Focus: Human transplant immunology research focused on deciphering immune signatures of acute cellular vs acute humoral allograft rejection after kidney transplantation leading to chronic rejection and graft loss. Role of induction therapy on innate and adaptive immune signatures and correlation with clinical outcomes.

Lab personnel: Camila Macedo MD, Elodie Bailly MD, Kevin Louis MD, Xinyan Gu BS, Research Tech.

Techniques involved: ex vivo investigation of peripheral blood and tissue biopsy using multi-onmics (spectral flow cytometry and immunohistochemistry, MSD, functional assays and co-cultures, scRNAseq, scATACseq), and clinical correlations/outcomes.

Resources: STI Biorepository (PBMC, Serum, Urine, Tissue Bx) and a comprehensive Clinical Database. NIAID funding.

Collaborators: A Zeevi (Histocompatibility); P Randhawa (Pathology lab); S Hariharan (Transplant Nephrology); H Singh (Systems Biology)

Selected Recent Publications:  Kidney International Reports (2019), Journal of American Society of Nephrology (2020), Journal of Clinical Investigation Insight (2021), Kidney International (2021 submitted); Invited Reviews: Transplantation (2021 invited), Trends in Molecular Medicine (2021 invited).

Oral presentations: @American Transplant Congress and @European Society of Transplantation.