Kent Weinhold
Joseph W. and Dorothy W. Beard Distinguished Professor of Experimental Surgery
Overview
The Weinhold Laboratory is currently focused on utilizing a comprehensive repertoire of highly standardized and formerly validated assay platforms to profile the human immune system in order to identify immunologic signatures that predict disease outcomes. These ongoing studies span a broad range of highly relevant clinical arenas, including: 1) cancer (non-small cell lung cancer, head and neck cancer, glioblastoma neoforme, ovarian cancer, and prostate cancer), 2) autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosis, multiple sclerosis, and myasthenia gravis), 3) pulmonary disease (idiopathic pulmonary fibrosis), 4) solid organ transplantation (lung, kidney, liver, and heart), and 5) inflammatory disorders.
Two of the areas that have been especially active over the past few years include the comprehensive immunologic profiling of cancer patients receiving so-called ‘immune checkpoint blockade’ therapies and the search for immune signatures in lung transplant recipients that track with resistance to CMV infection. The laboratory conducted immune monitoring studies associated with a Phase I trial of Ipilimumab (anti-CTLA-4) in a neoadjuvant setting for the treatment of non-small cell lung cancer (NSCLC). For this trial we extensively utilized several high parameter flow cytometry (PFC) platforms to follow activation, maturation, exhaustion, and proliferation patterns within CD4+ and CD8+ subsets of T-cells. We are also utilizing an intracellular cytokine staining (ICS) platform in efforts to detect anti-tumor associated antigen (TAA) responses by CD4+ and CD8+ T cells from peripheral blood mononuclear cells as well as lymphocytes infiltrating the patients’ tumor. These assays are designed to measure antigen-driven intracellular production of IFN-γ, TNF-α, and IL-2, as well as the degranulation marker CD107a. This strategy enables us to not only document individual cytokine responses, but to also assess (through Boolean gating) changes in relative polyfunctionality of the responses. We have also performed similar immune monitoring of a Phase II trial evaluating nivolumab (anti-PD-1) alone vs. combined nivolumamb + ipilimumab vs. avastin (bevacizamab) alone in patients with glioblastomas. In both studies, we are seeking to identify pharmacodynamics markers and immune correlates predictive of clinical responses. In completed studies of a cohort of lung transplant recipients, we identified specific polyfunctional signatures in CD4+ and CD8+ subsets against CMV pp65 and IE-1 antigens that tracked with resistance to CMV infection (manuscript in preparation). These findings now serve as the basis for a Phase I clinical trial to compare conventional 6-month chemoprophylaxis in lung transplant recipients versus a regimen dictated by the presence or absence of the predictive signatures. This trial is the principal component of a recently awarded Clinical Trials in Organ Transplantation or CTOT award made from the NIH to Duke (Scott Palmer, PI). Ongoing studies will test the hypothesis that these signatures that have been validated in lung transplant recipients will also predict resistance to CMV infection in the context of other solid organ transplants such as kidney, liver, and heart.Future studies will also attempt to identify predictive signatures for resistance to BK polyomavirus, the cause of graft threatening nephritis in kidney transplant recipients and cystitis in bone marrow transplant recipients.
Recent publications
Zidar, D.A., Mudd, J.C., Juchnowski, S., Lopes, J.P., Sparks, S., Park, S.S., Ishikawa, M., Osborne, R., Washam, J.B., Chan, C., Funderburg, N.T., Owoyele, A., Alaiti, M.A., Mayuga, M., Orringer, C., Costa, M.A., Simon, D.I., Tatsuoka, C., Califf, R.M., Newby, L.K., Lederman, M.M., and Weinhold, K.J. Altered maturation status and possible immune exhaustion of CD8 T lymphocytes in the peripheral blood of patients presenting with acute coronary syndromes. Arterioscler., Thromb., and Vasc. Biol. 36(2): 389-397, Feb. 2016 PMID: 26663396
Yi, J.S., Ready, N., Healy, P., Dumbauld, C., Berry, M., Shoemaker, D., Clarke, J., Crawford, J., Tong, B.C., Harpole, D., D’Amico, T.A., McSherry, F., Dunphy, F., McCall, S.J., Christensen, J.D., Wang, X, and Weinhold, K.J. Immune activation in early stage non-small cell lung cancer patients receiving neoadjuvant chemotherapy plus ipilimumab. Clin. Cancer Res. 23(24):7474-7482, 2017. PMCID: PMC5732888.
Reap, E., Suryadevera, C., Batuch, K., Sanchez-Perez, L., Archer, G., Schmittling, R., Norberg, P., Herndon II, J., Healy, P., Congdon, K., Gedeon, P., Campbell, O., Swartz, A., Riccione, K., Yi, J., Hossain-Ibrahim, M., Saraswathula, A., Nair, S., Anastasie, A., Broome, T., Weinhold, K.J., Desjardins, A., Vlahoviv, G., Mclendon, R., Firedman, H., Bigner, D., Fecci, P., Mitchell, D., and Sampson, J. Dendritic cells enhance polyfunctionality of adoptively transferred T cells which target cytomegalovirus in glioblastoma. Cancer Research 78(1):256-264, 2018. PMCID: PMC5754236.
Woroniecka, K., Chongsathidkiet, P., Rhodin, K., Kemeny, H., Dechant, C., Elsamadicy, A.A., Koyama, S., Jackson, C., Farber, H.S., Elsamadicy, A.A., Cui, X., Koyama, S., Jackson, C., Hansen, L., Bigner, D.D., Giles, A., Healy, P., Dranoff, G., Weinhold, K.J., Dunn, G.P., and Fecci, P.E. T cell exhaustion signatures vary with tumor type and are severe in glioblastoma. Clin. Cancer Res. Sep 1;24(17)4175-4186, 2018. PMCID: PMC6081269.
Weinhold, K.J., Bukowski, J.F., Brennan, T.V., Noveck, R.J., Staats, J.S., Lin, L., Stempora, L., Hammond, C., Wouters, A., Mojcik, C.F., Cheng, J., Collinge, M., Jesson, M.I., Hazra, A., Biswas, P., Lan, S., Clark, J.D., and Hodge, J.A. Reversibility of peripheral blood leukocyte phenotypic and functional changes after exposure to and withdrawal from tofacitinib, a Janus kinase inhibitor, in healthy volunteers. Clin. Immunology 191:10-20, June 19, 2018. PMCID: PMC6036921.
Berger, M., Oyeyemi, D, Olurinde, M.O., Whitson, H.E., Weinhold, K.J., Woldorff, M.G., Lipsitz, L.A., Moretti, E., Giattino, C.M., Rpberts, K.C., Zhou, J., Bunning, T., Ferrandino, M., Scheri, R.P., Cooter, M., Chan, C., Cabeza, R., Browndyke, J.N., Murdoch, D.M., Devinney, M.J., Shaw, L.M., Cohen, H.J., Mathew, J.P., and the INTUIT Investigators. The INTUIT Study: Investigating neuroinflammation underlying postoperative cognitive dysfunction. J. American Geriatrics Society 67940;794-798, 2019. PMCID: PMC6688749.
Berger, M., Murdoch, D., Staats, J., Chan, C., Thomas J., Garrigues, G., Browndyke, J., Cooter, M., Quinones, Q., Matthew, J., and Weinhold, K.J. Flow cytometry characterization of cerebrospinal fluid monocytes in patients with postoperative cognitive dysfunction (POCD): A pilot study. Anesthesia & Analgesia May 3, 2019 doi: 10.1213/ANE. PMCID: PMC6800758.
Nyanhete, T.E., Frisbee, A., Bradley, T., Faison, W.J., Robins, E., Payne, T.,Freel, S.A., Sawant, S., Weinhold, K.J., Wiehe, K., Haynes, B.F., Ferrari, G., Li, Q-J., Moody, M.A., and Tomaras, G.D. HLA class II-restricted CD8+T cells in HIV-1 virus controllers. Nat. Sci. Rep. 9(1):10165, 2019; PMCID: PMC6629643.
Yi, J.S., Rosa-Bray, M., Staats, J., Zakroysky, P., Chan, C., Russo, M., Dumbauld, C., White, S., Gierman, T., Weinhold, K.J., and Guptill, J.T. Establishment of normative ranges of the healthy immune system with comprehensive polychromatic flow cytometry profiling. PLoS One 14(12):e0225512, Dec.11, 2019. PMCID: PMC6905525.
Healy, Z.R., Weinhold, K.J., and Murdoch D.M. Transcriptional profiling of CD8+ CMV-specific T cell functional subsets obtained using a method for isolating high-quality RNA from fixed and permeabilized cells. Frontiers in Immunology 11:1859, Sep. 2, 2020. PMCID: PMC7492549.
Zhang, T., Harrison, M.R., O’Donnell, P.H., Ajjai, A., Hahn, N.M., Appleman, L.J., Cetnar, J., Burke, J.M., Fleming, M., Miloswsky. M., Mortazavi, A., Shore, N., Sonapavde, G., Schmidt, E., Bitman, B., Munugalavadla, V., Izumi, P., Patel, P., Staats, J., Chan, C., Weinhold, K.J.*and George, D.J.,*senior co-authors. A randomized phase 2 trial of pembrolizumab versus pembrolizumab and acalabrutinib in patients with platinum-resistant metastatic urothelial cancer. Cancer Oct.15, 2020 126(20):4485-4497. PMCID: PMC7590121
Salama, A.K.S., Palta, M., Rushing, C.N., Selim, M.A., Linnet, K.N., Czito, B.G., Yoo, D.S., Hanks, B.A., Beasley, G.M., Mosca, P., Dumbauld, C., Steadman, K.N., Yi, J.S., Weinhold, K.J., Tyler, D.S., Lee, W.T., and Brizel, D.M. Ipilimumab and radiation in patients with high risk resected or regionally advanced melanoma. Clin. Cancer Res. 1 March, 2021 27(5):1287-1295. PMCID: PMC8759408.
Li, Y., Yi, J.S., Russo, M.., Rosa-Bray, M., Weinhold. K.J., and Guptill, J.T. Normative dataset for plasma cytokines in healthy human adults. Data Brief 2021 Feb. 9;35:106857. PMCID: PMC7900339
White, S., Quinn, J., Enzor, E., Staats, J., Mosier, S.M., Almarode, J., Denny, T.N., Weinhold, K., Ferrari, G., and Chan, C. FlowKit: A Python toolkit for integrated manual and automated cytometry analysis workflows. Frontiers in Immunology 12:768541,Nov. 5, 2021. PMCID: PMC8602902.
Sung, B-Y., Lin, Y-H., Shah, P.D., Bieler, J.G., Palmer, S., Weinhold, K.J., Chang, H-R., Huang, H., Avery, R.K., Schneck, J., and Chiu, Y-L. Wnt activation promotes memory T cell polyfunctionality via epigenetic regulator PRMT1. J. Clin. Invest. 132(2):e140508, January 18, 2022. PMCID: PMC8759796.
Lusk, J.B., Quinones, Q.J., Staats, J.S., Weinhold, K.J., Grossi, P.M., Laskowitz, D.T., and James, M.L. Coupling hematoma evacuation with immune profiling for analysis of neuroinflammation after primary intracerebral hemorrhage: a pilot study. World Neurosurg. 2022 May;161:162-168 PMCID:PMID:35217228.
Brown, Landon C., Halabi, S., Somarelli, J., Humeniuk, M., Wu, Y., Oyekunle, T., Howard, L., Huang, J., Anand, M., Davies, C., Patel, P., Staats, J., Weinhold, K.J., Harrison, M.R., Zhang, T., George, D.J., and Armstrong, A.J. A phase 2 trial of avelumab in men with aggressive-variant or neuroendocrine prostate cancer. Prostate Cancer and Prostatic Diseases 25(4):762-769, 2022. PMCID: PMC8933335.
Khatri, A., Todd, J.L., Kelly, F.L., Nagler, A., Ji, Z., Jain, V., Gregory, S..G., Weinhold, K.J., and Palmer, S.M. JAK-STAT activation in basal cells contributes to cytotoxic T-cell mediated basal cell death in human chronic lung allograft dusfunction. JCI Insight 8(6) March 22, 2023 PMCID:PMC pending.
Zaffiri, L., Messinger, M., Staats, J.S., Patel, P., Palmer, S.M., Weinhold, K.J., Snyder, L.D., and Luftig, M.A. Evaluation of host cellular responses to Epstein-Barr virus (EBV) in adult lung transplant recipients with EBV-associated diseases. J. Med. Virol. 95(4):e28724, 2023.
Positions
Professor in Surgery in the School of Medicine
1999 School of Medicine
Joseph W. and Dorothy W. Beard Distinguished Professor of Experimental Surgery in the School of Medicine
2009 School of Medicine
Professor of Immunology in the School of Medicine
2001 School of Medicine
Professor in Pathology in the School of Medicine
2014 School of Medicine
Member of the Duke Human Vaccine Institute in the School of Medicine
2006 School of Medicine
Member of the Duke Cancer Institute in the School of Medicine
2013 School of Medicine
Education
Ph.D. 1979
1979 Thomas Jefferson University
Publications, Grants & Awards
- Grants (89)
- Academics Articles (190)
- Conference Pages (46)
- Book Sections (1)
National Institutes of Health
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Department of Defense
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Torque Bio
American Association for Cancer Research
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Fred Hutchinson Cancer Center
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Department of Defense
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Department of Defense
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Sontag Foundation
Foundation for Anesthesia Education and Research
National Institutes of Health
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Society of Cardiovascular Anesthesiologists
Myasthenia Gravis Foundation
National Institutes of Health
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Bristol-Myers Squibb Company
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Fred Hutchinson Cancer Research Center
Fred Hutchinson Cancer Research Center
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ImmusanT
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World Neurosurg
Prostate Cancer Prostatic Dis
J Clin Invest
Clinical Cancer Research
Frontiers in Immunology
Frontiers in Immunology
Scientific Reports
Journal of the American Geriatrics Society
Clinical Cancer Research
Clinical Cancer Research
Frontiers in Neurology
Arterioscler Thromb Vasc Biol
American Journal of Respiratory and Critical Care Medicine
Neurology: Neuroimmunology and Neuroinflammation
J Proteome Res
Clinical Cancer Research
Scientific Reports
Cancer Informatics
Mucosal Immunol
Transplantation
Annals of Surgical Oncology
Cytometry A
Cytometry A
Am J Transplant
Aids Research and Therapy
Journal of Acquired Immune Deficiency Syndromes
The Journal of Infectious Diseases
Aids Research and Human Retroviruses
Bmc Immunology
Proceedings of the National Academy of Sciences of the United States of America
Aids Research and Human Retroviruses
The Journal of Infectious Diseases
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Human Immunology
The Journal of Infectious Diseases
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Journal of Acquired Immune Deficiency Syndromes
Aids Research and Human Retroviruses
Immunology Letters
Pediatric Infectious Disease Journal
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Aids Research and Human Retroviruses
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Immunologic Research
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Clinical and Diagnostic Laboratory Immunology
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Proceedings of the National Academy of Sciences of the United States of America
The Journal of Clinical Investigation
Aids Research and Human Retroviruses
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Journal of Surgical Research
American Journal of Epidemiology
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Aids Research and Human Retroviruses
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Proceedings of the National Academy of Sciences of the United States of America
Aids Research and Human Retroviruses
Springer Seminars in Immunopathology
The Journal of Clinical Investigation
Annals of Internal Medicine
Aids Research and Human Retroviruses
The Journal of Infectious Diseases
Journal of Virology
Clinical and Experimental Immunology
The Journal of Infectious Diseases
Cellular Immunology
Aids Research and Human Retroviruses
Aids Research and Human Retroviruses
The Journal of Infectious Diseases
Journal of Acquired Immune Deficiency Syndromes
Aids Research and Human Retroviruses
Aids Research and Human Retroviruses
Aids Research and Human Retroviruses
The Journal of Experimental Medicine
Pediatric Infectious Disease Journal
Aids Research and Human Retroviruses
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Science (New York, N.Y.)
Proceedings of the National Academy of Sciences of the United States of America
International Immunology
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Cellular Immunology
Aids Research and Human Retroviruses
Science (New York, N.Y.)
Biotechnology Therapeutics
The New England Journal of Medicine
The Journal of Immunology
Proceedings of the National Academy of Sciences of the United States of America
Aids Research and Human Retroviruses
Science (New York, N.Y.)
American Journal of Hematology
The Journal of Immunology
The Journal of Pediatrics
Developments in Biological Standardization
Journal of Biological Response Modifiers
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The Journal of Experimental Medicine
Aids Research and Human Retroviruses
Aids Research and Human Retroviruses
American Journal of Hematology
Lancet (London, England)
Proceedings of the National Academy of Sciences of the United States of America
Aids Research and Human Retroviruses
Advances in Experimental Medicine and Biology
Thymus
Antimicrobial Agents and Chemotherapy
Proceedings of the National Academy of Sciences of the United States of America
Proceedings of the National Academy of Sciences of the United States of America
Virology
Clinical Immunology Newsletter
Surgical Forum
The American Journal of Pediatric Hematology/Oncology
Aids Research and Human Retroviruses
Aids Research and Human Retroviruses
Aids Research and Human Retroviruses
Science (New York, N.Y.)
Proceedings of the National Academy of Sciences of the United States of America
Lancet (London, England)
Lancet (London, England)
Journal of the National Cancer Institute
Journal of the National Cancer Institute
Journal of the National Cancer Institute
Proceedings of the National Academy of Sciences of the United States of America
Journal of the National Cancer Institute
Zeitschrift Fur Naturforschung. Section C, Biosciences
Cancer Investigation
Cancer Research
Journal of the National Cancer Institute
Journal of the National Cancer Institute
Advances in Cancer Research
The Journal of Immunology
Journal of Medical Microbiology
The Journal of Experimental Medicine
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
American Journal of Respiratory and Critical Care Medicine
Muscle & Nerve
International Journal of Radiation Oncology, Biology, Physics
American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
Aids Research and Human Retroviruses
American Journal of Respiratory and Critical Care Medicine
Retrovirology
Journal of Acquired Immune Deficiency Syndromes
Cytometry. Part B, Clinical Cytometry
Faseb Journal
Faseb Journal
11E COLLOQUE DES CENT GARDES
Faseb Journal
RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES
Aids Research and Human Retroviruses
Aids Research and Human Retroviruses
Journal of Cellular Biochemistry
Aids Research and Human Retroviruses
Journal of Cellular Biochemistry
Journal of Cellular Biochemistry
Aids Research and Human Retroviruses
Clinical Research
Faseb Journal
Aids Research and Human Retroviruses
Journal of Biological Response Modifiers
Journal of Cellular Biochemistry
Clinical Research
Zentralblatt Fur Bakteriologie Mikrobiologie Und Hygiene Series a Medical Microbiology Infectious Diseases Virology Parasitology
Proceedings of the American Association for Cancer Research
Federation Proceedings
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