David A. Hildeman, PhD

Professor, UC Department of Pediatrics

david.hildeman@cchmc.org

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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

Fibrosis, Immunobiology

Publications

Sustained and Boosted Antibody Responses in Breast Milk After Maternal SARS-CoV-2 Vaccination. Ware, J; McElhinney, K; Latham, T; Lane, A; Dienger-Stambaugh, K; Hildeman, D; Spearman, P; Ware, RE. Breastfeeding Medicine. 2023; 18:612-620.

Single-cell transcriptomic analysis of renal allograft rejection reveals insights into intragraft TCR clonality. Shi, T; Burg, AR; Caldwell, JT; Roskin, KM; Castro-Rojas, CM; Chukwuma, PC; Gray, GI; Foote, SG; Alonso, JA; Cuda, CM; et al. The Journal of Clinical Investigation. 2023; 133:e170191.

Effects of invivo CXCR4 blockade and proteasome inhibition on bone marrow plasma cells in HLA-sensitized kidney transplant candidates. Rossi, AP; Tremblay, S; Castro-Rojas, CM; Burg, AA; Roskin, KM; Gehman, JM; Rike-Shields, A; Alloway, RR; Brailey, P; Allman, D; et al. American Journal of Transplantation. 2023; 23:759-775.

Apoptotic cell death in disease-Current understanding of the NCCD 2023. Vitale, I; Pietrocola, F; Guilbaud, E; Aaronson, SA; Abrams, JM; Adam, D; Agostini, M; Agostinis, P; Alnemri, ES; Altucci, L; et al. Cell Death and Differentiation. 2023; 30:1097-1154.

T-cell infiltrate intensity is associated with delayed response to treatment in late acute cellular rejection in pediatric liver transplant recipients. Peters, AL; Rogers, M; Begum, G; Sun, Q; Fei, L; Leino, D; Hildeman, D; Woodle, ES. Pediatric Transplantation. 2023; 27:e14475.

Elevated CD153 Expression on Aged T Follicular Helper Cells is Vital for B cell Responses. Thomas, AL; Wayman, JA; Almanan, M; Bejjani, AT; Miraldi, ER; Chougnet, CA; Hildeman, DA. 2023; 4:2023.03.17.533214.

An atlas of gene regulatory networks for memory CD4 + T cells in youth and old age. Wayman, JA; Thomas, A; Bejjani, A; Katko, A; Almanan, M; Godarova, A; Korinfskaya, S; Cazares, TA; Yukawa, M; Kottyan, LC; et al. 2023; 4:2023.03.07.531590.

Farnesoid X receptor antagonizes macrophage-dependent licensing of effector T lymphocytes and progression of sclerosing cholangitis. Shi, T; Malik, A; vom Hofe, AY; Matuschek, L; Mullen, M; Lages, CS; Kudira, R; Singh, R; Zhang, W; Setchell, KD R; et al. Science Translational Medicine. 2022; 14:eabi4354.

Naturally-aged microglia exhibit phagocytic dysfunction accompanied by gene expression changes reflective of underlying neurologic disease. Thomas, AL; Lehn, MA; Janssen, EM; Hildeman, DA; Chougnet, CA. Scientific Reports. 2022; 12:19471.

Role of transcription factor RUNX1 in the maintenance of T helper cell epigenome and rapid recall response. Korinfskaya, S; Kotliar, M; Katko, A; Hildeman, D; Miraldi, ER; Barski, A. Journal of immunology (Baltimore, Md. : 1950). 2022; 208:56.13.