Faculty

Albert D. Donnenberg, PhD Professor of Medicine - School of Medicine and Department of Infectious Diseases and Microbiology - Graduate School of Public Health (Secondary Appointment) Director, UPCI Flow Cytometry Laboratory Laboratory Director, UPMC Hematopoietic Stem Cell Laboratory Deputy Director, UPCI Hematopoietic Stem Cell Transplantation Program E-mail: donnenbergad@msx.upmc.edu Phone: 412-623-3256 Fax: 412-623-7778 Address: Hillman Cancer Center 5117 Centre Ave., Suite 4.24c Pittsburgh, PA 15213

Education

BA; Philosophy, University of Colorado, Boulder; 1973
PhD; Infectious Disease Epidemiology, Johns Hopkins University; 1980

Research Interests

The major efforts of Dr. Donnenberg's research laboratory are focused toward four projects, all of which are presently funded by NIH grants:

Functional significance of T-cell activation markers.  Through ongoing studies in BMT recipients and HIV infected subjects he is providing evidence that classical markers of memory and naïve T cells, as well as cell surface proteins that have been regarded as markers of immune activation, can be better understood in the context of T cell poiesis, the stringency of requirements for immune activation, and resistance or susceptibility to apoptosis.  In the setting of HIV infection he is investigating how apoptosis and antigen driven activation are modulated by antiretroviral therapy.

T-cell turnover in SIV infection.  These studies, in the rhesus macaque, dovetail with the studies described above.  Dr. Donnenberg is attempting to provide direct evidence that in times of lymphopoietic stress (e.g. cancer chemotherapy, HIV infection), extrathymic T-cell generation is prominent pauci-thymic adults.  He has also used the SIV model to evaluate dendritic cell based antiviral therapy.  His contribution to this collaborative effort has been to develop rare event multiparameter flow cytometry techniques to detect and characterize injected DCs after they have homed to the lymph nodes.  He has since applied these methods to many other problems including detection and characterization of residual leukocytes in leukocyte depleted platelet components, and subset analysis of antigen-specific T cells using peptide-MHC class I tetramer technology.

Role of p-gp in resistance to immunosuppressive agents.  These studies, performed in collaboration with Drs. Gilbert Burkart and Bartley Griffith, examine the role of the multi-drug resistance pump P-gp in the ability of T cells to resist the effects of immunosuppressive drugs.  Studies are being conducted on BAL samples collected from lung allograft recipients, and P-gp function is being compared in graft infiltrating and peripheral T cell subsets.

Immunologic consequences of autologous transplantation in systemic sclerosis:  In this study, Dr. Donnenberg will be examining immune reconstitution in patients who have received lymphoablative therapy and T-cell depleted progenitor cell autografts.

Recent Publications

• Triulzi, D.J., Meyer, E.M., and Donnenberg, A.D.  (2000). Leukocyte subset analysis of leukoreduced platelet components. Transfusion 40:771-780.

• deMagalhaes-Silverman, M., Donnenberg, A.D., Lembersky, B., Elder, E., Lister, J., Rybka, W., Whiteside, T., and Ball, E.D.  (2000).  Post-transplant adoptive immunotherapy with activated natural killer cells in patients with metastatic breast cancer. J. Immunother. 23:154-160.

• Barratt-Boyes, S.M., Zimmer, M.I., Harshyne, L.A., Meyer, M., Watkins, S.C., Capuano, S., Murphey-Corb, M., Falo, L.D., and Donnenberg, A.D.   (2000).  Maturation and trafficking of monocyte-derived dendritic cells in monkeys: implications for dendritic cell-based vaccines.  J. Immunol. 164:2487-2495.

• Hoffman, T.K., Donnenberg, V.S., Friebe-Hoffmann, U., Meyer, E.M., Rinaldo, C.R., DeLeo, A.B., Whiteside, T.L., Donnenberg, A.D.  (2000).  Rapid Communication:  Competition of peptide-MHC Class I tetrameric complexes with anti-CD3 provides evidence for specificity of peptide binding to the TCR complex.  Cytometry  41:321-328.

• Donnenberg, V.S., O'Connell, P.J., Logar, A.J., Zeevi, A., Thomson, A.W., and Donnenberg, A.D.  (2001).  Rare event analysis of circulating human dendritic cell subsets and their presumptive mouse counterparts.  Transplantation 72:1946-1951.

• Donnenberg, V.S. and Donnenberg, A.D. (2005) Multiple drug resistance in cancer revisited:  the cancer stem cell hypothesis.  J. Clin. Pharmacol.  45:872-877.
• Hoffmann, T.K., Bier, H., Donnenberg, A.D., Whiteside, T.L., and De Leo, A.B.  (2005)  p53 as an immunotherapeutic target in head and neck cancer.  Adv. Otorhinolaryngol.  62:151-160.
• Macedo, C., Donnenberg, A., Popescu, I., Reyes, J., Abu-Elmagd, K., Shapiro, R., Zeevi, A., Fung, J.J., Storkus, W.J., and Metes, D.  (2005) EBV-specific memory CD8+ T cell phenotype and function in stable solid organ transplant patients.  Transpl. Immunol.  14:109-116.