Immunobiology
Hildeman Lab

Hildeman Research Lab

The Hildeman Lab studies the molecular mechanisms controlling T cell development and homeostasis. The lab uses molecular, cellular, and genetic approaches in animal models and human samples to investigate cell signaling, apoptosis, and the development of memory. The lab also is developing and evaluating novel therapeutic approaches to eliminate T and B cells causing autoimmunity and solid organ transplant rejection.

Our current projects in the lab include:

  1. The role of Bcl-2 family members in control of T cell development, peripheral homeostasis, and development of cell memory
  2. The homeostasis and function of regulatory T cells and dendritic cells in aging
  3. Single cell analysis of transplant rejection
  4. Mechanistic targeting of plasma cells in transplant rejection and autoimmunity

Publications

Ochoa, TA; Rossi, A; Woodle, ES; Hildeman, D; Allman, D. The Proteasome Inhibitor Bortezomib Induces p53-Dependent Apoptosis in Activated B Cells. Journal of immunology (Baltimore, Md. : 1950). 2024; 212:154-164.

Khorki, ME; Shi, T; Cianciolo, EE; Burg, AR; Chukwuma, PC; Picarsic, JL; Morrice, MK; Woodle, ES; Maltzman, JS; Ferguson, A; et al. Prior viral infection primes cross-reactive CD8+ T cells that respond to mouse heart allografts. Frontiers in Immunology. 2023; 14:1287546.

Thomas, AL; Godarova, A; Wayman, JA; Miraldi, ER; Hildeman, DA; Chougnet, CA. Accumulation of immune-suppressive CD4 + T cells in aging - tempering inflammaging at the expense of immunity. Seminars in Immunology. 2023; 70:101836.

Mahajan, S; Alexander, A; Koenig, Z; Saba, N; Prasanphanich, N; Hildeman, DA; Chougnet, CA; DeFranco, E; Andorf, S; Tilburgs, T. Antigen-specific decidual CD8+ T cells include distinct effector memory and tissue-resident memory cells. JCI insight. 2023; 8:e171806.

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

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

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

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

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

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

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

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

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

Carlucci, PM; Li, J; Fava, A; Deonaraine, KK; Wofsy, D; James, JA; Putterman, C; Diamond, B; Davidson, A; Fine, DM; et al. High incidence of proliferative and membranous nephritis in SLE patients with low proteinuria in the Accelerating Medicines Partnership. Rheumatology. 2022; 61:4335-4343.

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

Shanmuganad, S; Hummel, SA; Varghese, V; Hildeman, DA. Bcl-2 Is Necessary to Counteract Bim and Promote Survival of TCRαβ+CD8αα+ Intraepithelial Lymphocyte Precursors in the Thymus. Journal of immunology (Baltimore, Md. : 1950). 2022; 208:651-659.

Shi, T; Roskin, K; Baker, BM; Woodle, ES; Hildeman, D. Advanced Genomics-Based Approaches for Defining Allograft Rejection With Single Cell Resolution. Frontiers in Immunology. 2021; 12:750754.

Thomas, AL; Alarcon, PC; Divanovic, S; Chougnet, CA; Hildeman, DA; Moreno-Fernandez, ME. Implications of Inflammatory States on Dysfunctional Immune Responses in Aging and Obesity. Frontiers in Aging. 2021; 2:732414.

Rossi, AP; Alloway, RR; Hildeman, D; Woodle, ES. Plasma cell biology: Foundations for targeted therapeutic development in transplantation. Immunological Reviews. 2021; 303:168-186.

Davis, G; York, AJ; Bacon, WC; Lin, SC; McNeal, MM; Yarawsky, AE; Maciag, JJ; Miller, JL C; Locker, KC S; Bailey, M; et al. Seroprevalence of SARS-CoV-2 infection in Cincinnati Ohio USA from August to December 2020. Editor, Kumar B. PloS one. 2021; 16:e0254667.

Moreno-Fernandez, ME; Sharma, V; Stankiewicz, TE; Oates, JR; Doll, JR; Damen, MS M A; Almanan, MA T A; Chougnet, CA; Hildeman, DA; Divanovic, S. Aging mitigates the severity of obesity-associated metabolic sequelae in a gender independent manner. Nutrition and Diabetes. 2021; 11:15.

Kirk, AD; Adams, AB; Durrbach, A; Ford, ML; Hildeman, DA; Larsen, CP; Vincenti, F; Wojciechowski, D; Woodle, ES. Optimization of de novo belatacept-based immunosuppression administered to renal transplant recipients. American Journal of Transplantation. 2021; 21:1691-1698.

Newton, HS; Gawali, VS; Chimote, AA; Lehn, MA; Palackdharry, SM; Hinrichs, BH; Jandarov, R; Hildeman, D; Janssen, EM; Wise-Draper, TM; et al. PD1 blockade enhances K+ channel activity, Ca2+ signaling, and migratory ability in cytotoxic T lymphocytes of patients with head and neck cancer. Journal for ImmunoTherapy of Cancer. 2020; 8:e000844.

Almanan, M; Raynor, J; Ogunsulire, I; Malyshkina, A; Mukherjee, S; Hummel, SA; Ingram, JT; Saini, A; Xie, MM; Alenghat, T; et al. IL-10-producing Tfh cells accumulate with age and link inflammation with age-related immune suppression. Science Advances. 2020; 6:eabb0806.

Woodle, ES; Tremblay, S; Rossi, A; Rojas, CC; Alloway, R; Roskin, K; Allman, D; Hildeman, D. Plasma cell targeting to prevent antibody-mediated rejection. American Journal of Transplantation. 2020; 20 Suppl 4:33-41.

Newton, H; Gawali, VS; Chimote, AA; Lehn, M; Palackdharry, S; Hildeman, D; Janssen, E; Wise-Draper, T; Conforti, L. Pembrolizumab treatment increases K+ channel function and calcium fluxes in cytotoxic T cells of head and neck cancer patients. Journal of immunology (Baltimore, Md. : 1950). 2020; 204:165.41.

Castro-Rojas, CM; Godarova, A; Shi, T; Hummel, SA; Shields, A; Tremblay, S; Alloway, RR; Jordan, MB; Woodle, ES; Hildeman, DA. mTOR Inhibitor Therapy Diminishes Circulating CD8+ CD28- Effector Memory T Cells and Improves Allograft Inflammation in Belatacept-refractory Renal Allograft Rejection. Transplantation. 2020; 104:1058-1069.

Li, K; Ladle, BH; Kurtulus, S; Sholl, A; Shanmuganad, S; Hildeman, DA. T-cell receptor signal strength and epigenetic control of Bim predict memory CD8+ T-cell fate. Cell Death and Differentiation. 2020; 27:1214-1224.

Raynor, J; Lin, A; Hummel, SA; Lampe, K; Jordan, M; Hoebe, K; Hildeman, DA. The Variable Genomic NK Cell Receptor Locus Is a Key Determinant of CD4+ T Cell Responses During Viral Infection. Frontiers in Immunology. 2020; 11:197.

Tremblay, S; Driscoll, JJ; Rike-Shields, A; Hildeman, DA; Alloway, RR; Girnita, AL; Brailey, PA; Woodle, ES. A prospective, iterative, adaptive trial of carfilzomib-based desensitization. American Journal of Transplantation. 2020; 20:411-421.

Science Blog

Research Reveals Novel Insights into Transplant Rejection and New Drug Development Targets
Surgical Science

Research Reveals Novel Insights into Transplant Rejection and New Drug Development Targets

David A. Hildeman, PhD6/28/2023

New Concept for Boosting Flu Vaccine Power Also Might Apply to Future COVID-19 Vaccines
Infectious Diseases and Vaccines

New Concept for Boosting Flu Vaccine Power Also Might Apply to Future COVID-19 Vaccines

David A. Hildeman, PhD7/29/2020

Contact Us

A photo of David A. Hildeman.
David A. Hildeman, PhD
Phone: 513-636-3923
Email: david.hildeman@cchmc.org

Lab Members

Research Associate: Ashley Burg
Research Assistants: Autumn Ferguson, Sarah Evans
Graduate Students: Tiffany Shi, Ramiah Caine
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