David A. Hildeman, PhD

Professor, UC Department of Pediatrics

david.hildeman@cchmc.org

About

Biography

My lab is interested in understanding mechanisms underlying lymphocyte development, homeostasis and function. We are studying these processes in the context of aging, infection and vaccination as well as transplant rejection.

Our long-term goal is to identify molecular mechanisms that can be exploited to boost immunity, such as vaccine responsiveness. The mechanisms could also be manipulated to decrease auto-immunity or allo-immunity like autoimmune disease, transplant rejection or allergic reactions.

One of the reasons I love doing immunology research is because I learn new things about the complexity of the immune system and how it has developed to provide protective immunity while avoiding autoimmunity. Beyond the outstanding research environment, phenomenal PhD program, and the cutting-edge core facilities, another reason for doing research at the Cincinnati Children’s Hospital Medical Center is the collaborative environment.

For example, our work on aging has been a close collaboration between my lab and Dr. Claire Chougnet’s lab. Furthermore, our research in transplantation started as the result of a phone call from a world-renowned transplant surgeon at the University of Cincinnati about joining forces on T-cell mediated kidney rejection.

One of the most notable findings my team and I have uncovered includes a function for the pro-apoptotic molecule Bim in driving the “crash” of T-cells after the pinnacle of an immune response. We also discovered a common gamma chain cytokine/STAT5/Bcl2 network that antagonizes Bim and is needed for developing protective T-cell memory.

I am a Fellow of the Graduate School at the University of Cincinnati, the PI of a T32 Training Grant, and served as a permanent member of the Cellular and Molecular Immunology-B National Institutes of Health (NIH) study section as well as Chair of several NIH study sections.

I have more than 20 years of experience in the immunology field and started working at Cincinnati Children’s Hospital Medical Center in 2002. My research has been published in many journals, including PNAS, Science Advances, Cell Death and Differentiation, and American Journal of Transplantation.

Interests

T cells; autoimmunity; sex differences in immune responses; apoptosis

Interests

Molecular factors that control the decision between tolerance and immunity within T lymphocytes; staphylococcal enterotoxins, recombinant vaccinia viruses, lymphocytic choriomeningitis virus and MHC tetrameric reagents; antigen -specific T cell responses; tolerance centers on regulation of mechanisms that control the survival and death of activated T cells in vivo, namely Bcl-2 and its antagonist Bim; manipulation and regulation of antigen-specific T cell responses via novel vaccine strategies to either induce tolerance or enhance immunity; mechanisms underlying sex-based differences in T cell responses and how these differences relate to autoimmune disease.

Research Areas

Publications

Leveraging Heterologous Immunity to Provide Insights into Alloreactivity. Burg, A; Brambley, C; Ferguson, A; Cianciolo, E; Caine, R; Shi, T; Khorki, M; Chukwuma, P; Woodle, E; Maltzman, J; Baker, B; Hildeman, D. American Journal of Transplantation. 2025; 25:s94.

Co-Stimulatory Blockade Prevents Intragraft Accrual of Class-Switched, Activated B Cells and Th17 T Cells and Promotes Accrual of Tregs. Caldwell, J; Shi, T; Burg, A; Roskin, K; Shields, AR; Woodle, E; Hildeman, D. American Journal of Transplantation. 2025; 25:s391-s392.

Integration of scRNAseq Analyses of Kidney and Liver Allograft Rejection Enables Identification of Common and Unique Characteristics. Caldwell, J; Peters, A; DePasquale, E; Burg, A; Caine, R; Begum, G; Woodle, E; Hildeman, D. American Journal of Transplantation. 2025; 25:s304.

Human Long-Lived Plasma Cells Acquire Resistance to Proteasome Inhibitor-Based Desensitization Treatment by Upregulating Autophagy. Burg, A; Ferguson, A; Rossi, A; Shields, AR; Allman, D; Hildeman, D; Woodle, E. American Journal of Transplantation. 2025; 25:s315-s316.

Multiome Sequencing of Chronic Ductopenic Rejection Reveals Roles for Th2 Immunity and Activated Fibroblasts in Cholangiocyte Injury. Peters, AL; DePasquale, E; Begum, G; Seraphine, K; Steinkamp, S; Huppert, S; Woodle, E; Hildeman, D. American Journal of Transplantation. 2025; 25:s245.

Single-Cell RNA/TCR Sequencing: Do Urinary CD8+ T Cell Populations Accurately Reflect Transcriptional Profiling of Allograft Infiltrating CD8+ T Cell Populations?. Caine, R; Shi, T; Burg, A; Alloway, R; Shields, AR; Roskin, K; Woodle, E; Hildeman, D. American Journal of Transplantation. 2025; 25:s8-s9.

HLA T Cell Epitope Mismatch and the Risk of Acute Rejection Among Participants in the Astellas Double Blind Randomized Early Corticosteroid Cessation Trial. Lan, JH; Tran, J; AvGay, G; Niemann, M; Bandstra, S; Alloway, RR; First, M; Fitzsimmons, B; Hildeman, D; Gill, JS; Woodle, E. American Journal of Transplantation. 2025; 25:s116.

Deep immunophenotyping reveals circulating activated lymphocytes in individuals at risk for rheumatoid arthritis. Inamo, J; Keegan, J; Griffith, A; Ghosh, T; Horisberger, A; Howard, K; Pulford, JF; Murzin, E; Hancock, B; Dominguez, ST; Tuschl, T; Wofsy, D; Woodle, S; Wyse, A. The Journal of Clinical Investigation. 2025; 135:e185217.

Gucy1α1 specifically marks kidney, heart, lung and liver fibroblasts. Rudman-Melnick, V; Vanhoutte, D; Stowers, K; Sargent, M; Adam, M; Ma, Q; Perl, AK T; Miethke, AG; Burg, A; Shi, T; Hildeman, DA; Woodle, ES S; Kofron, JM; Devarajan, P. Scientific Reports. 2024; 14:29307.