Kent James Weinhold, PhD

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Professor of Surgery
Professor of Immunology
Professor in Pathology
Chief, Division of Surgical Sciences
Department / Division:
Surgery / Surgical Sciences
Address:
204 Surg Oncol Res Fac
Durham, NC 27710
Office Telephone:
(919) 684-5572
Training:
  • PhD, Thomas Jefferson University, 1979
Research Interests:

In addition to their ongoing HIV/AIDS research projects, the Weinhold laboratory is presently focused on utilizing a comprehensive repertoire of highly standardized and formally validated assay platforms to profile the human immune system in order to identify immunologic signatures that predict disease outcomes. These are the very same assay platforms that have proven extraordinarily useful in profiling HIV-specific immune responses during acute and chronic HIV infection as well as in the context of elite virologic control.  The 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, and prostate cancer), 2) autoimmune disease (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) rare diseases (Pompe disease).

Two of the areas that have been especially active over the past year 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 is conducting 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 are extensively utilized several polychromatic 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 CD107. 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 are performing 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 recently completed studies in 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.  Other human diseases that are presently being subjected to comprehensive immune profiling by the laboratory include idiopathic pulmonary fibrosis (IPF), myasthenia gravis

Representative Publications:
  • Freel, SA; Lamoreaux, L; Chattopadhyay, PK; Saunders, K; Zarkowsky, D; Overman, RG; Ochsenbauer, C; Edmonds, TG; Kappes, JC; Cunningham, CK; Denny, TN; Weinhold, KJ; Ferrari, G; Haynes, BF; Koup, RA; Graham, BS; Roederer, M; Tomaras, GD. Phenotypic and functional profile of HIV-inhibitory CD8 T cells elicited by natural infection and heterologous prime/boost vaccination. Journal of Virology. 2010;84:4998-5006.  Abstract
  • Goonetilleke, N; Liu, MK; Salazar-Gonzalez, JF; Ferrari, G; Giorgi, E; Ganusov, VV; Keele, BF; Learn, GH; Turnbull, EL; Salazar, MG; Weinhold, KJ; Moore, S; CHAVI Clinical Core B, ; Letvin, N; Haynes, BF; Cohen, MS; Hraber, P; Bhattacharya, T; Borrow, P; Perelson, AS; Hahn, BH; Shaw, GM; Korber, BT; McMichael, AJ. The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection. Journal of Experimental Medicine. 2009;206:1253-1272.  Abstract
  • Murdoch, DM; Suchard, MS; Venter, WD; Mhlangu, P; Ottinger, JS; Feldman, C; Van Rie, A; Glencross, DK; Stevens, WS; Weinhold, KJ. Polychromatic immunophenotypic characterization of T cell profiles among HIV-infected patients experiencing immune reconstitution inflammatory syndrome (IRIS). AIDS Research and Therapy. 2009;6:16.  Abstract
  • Shen, X; Parks, RJ; Montefiori, DC; Kirchherr, JL; Keele, BF; Decker, JM; Blattner, WA; Gao, F; Weinhold, KJ; Hicks, CB; Greenberg, ML; Hahn, BH; Shaw, GM; Haynes, BF; Tomaras, GD. In vivo gp41 antibodies targeting the 2F5 monoclonal antibody epitope mediate human immunodeficiency virus type 1 neutralization breadth. Journal of Virology. 2009;83:3617-3625.  Abstract
  • Spearman, P; Kalams, S; Elizaga, M; Metch, B; Chiu, YL; Allen, M; Weinhold, KJ; Ferrari, G; Parker, SD; McElrath, MJ; Frey, SE; Fuchs, JD; Keefer, MC; Lubeck, MD; Egan, M; Braun, R; Eldridge, JH; Haynes, BF; Corey, L; NIAID HIV Vaccine Trials Network. Safety and immunogenicity of a CTL multiepitope peptide vaccine for HIV with or without GM-CSF in a phase I trial. Vaccine. 2009;27:243-249.  Abstract
  • Alam, SM; Scearce, RM; Parks, RJ; Plonk, K; Plonk, SG; Sutherland, LL; Gorny, MK; Zolla-Pazner, S; Vanleeuwen, S; Moody, MA; Xia, SM; Montefiori, DC; Tomaras, GD; Weinhold, KJ; Karim, SA; Hicks, CB; Liao, HX; Robinson, J; Shaw, GM; Haynes, BF. Human immunodeficiency virus type 1 gp41 antibodies that mask membrane proximal region epitopes: antibody binding kinetics, induction, and potential for regulation in acute infection. Journal of Virology. 2008;82:115-125.  Abstract
  • Gasper-Smith, N; Crossman, DM; Whitesides, JF; Mensali, N; Ottinger, JS; Plonk, SG; Moody, MA; Ferrari, G; Weinhold, KJ; Miller, SE; Reich, CF; Qin, L; Self, SG; Shaw, GM; Denny, TN; Jones, LE; Pisetsky, DS; Haynes, BF. Induction of plasma (TRAIL), TNFR-2, Fas ligand, and plasma microparticles after human immunodeficiency virus type 1 (HIV-1) transmission: implications for HIV-1 vaccine design. Journal of Virology. 2008;82:7700-7710.  Abstract
  • Gorse, GJ; Baden, LR; Wecker, M; Newman, MJ; Ferrari, G; Weinhold, KJ; Livingston, BD; Villafana, TL; Li, H; Noonan, E; Russell, ND; HIV Vaccine Trials Network. Safety and immunogenicity of cytotoxic T-lymphocyte poly-epitope, DNA plasmid (EP HIV-1090) vaccine in healthy, human immunodeficiency virus type 1 (HIV-1)-uninfected adults. Vaccine. 2008;26:215-223.  Abstract
  • Russell, ND; Graham, BS; Keefer, MC; McElrath, MJ; Self, SG; Weinhold, KJ; Montefiori, DC; Ferrari, G; Horton, H; Tomaras, GD; Gurunathan, S; Baglyos, L; Frey, SE; Mulligan, MJ; Harro, CD; Buchbinder, SP; Baden, LR; Blattner, WA; Koblin, BA; Corey, L; National Institute of Allergy and Infectious Diseases HIV Vaccine Trials Network. Phase 2 study of an HIV-1 canarypox vaccine (vCP1452) alone and in combination with rgp120: negative results fail to trigger a phase 3 correlates trial. JAIDS: Journal of Acquired Immune Deficiency Syndromes. 2007;44:203-212.  Abstract
  • Mulligan, MJ; Russell, ND; Celum, C; Kahn, J; Noonan, E; Montefiori, DC; Ferrari, G; Weinhold, KJ; Smith, JM; Amara, RR; Robinson, HL; NIH/NIAID/DAIDS HIV Vaccine Trials Network. Excellent safety and tolerability of the human immunodeficiency virus type 1 pGA2/JS2 plasmid DNA priming vector vaccine in HIV type 1 uninfected adults. AIDS Research and Human Retroviruses. 2006;22:678-683.  Abstract
  • Betts, MR; Exley, B; Price, DA; Bansal, A; Camacho, ZT; Teaberry, V; West, SM; Ambrozak, DR; Tomaras, G; Roederer, M; Kilby, JM; Tartaglia, J; Belshe, R; Gao, F; Douek, DC; Weinhold, KJ; Koup, RA; Goepfert, P; Ferrari, G. Characterization of functional and phenotypic changes in anti-Gag vaccine-induced T cell responses and their role in protection after HIV-1 infection. Proceedings of the National Academy of Sciences of USA. 2005;102:4512-4517.  Abstract
  • Kaplan, SS; Ferrari, G; Wrin, T; Hellmann, NS; Tomaras, GD; Gryszowka, VE; Fiscus, SA; Weinhold, KJ; Hicks, CB. Longitudinal assessment of immune response and viral characteristics in HIV-infected patients with prolonged CD4(+)/viral load discordance. AIDS Research and Human Retroviruses. 2005;21:13-16.  Abstract
  • Ferrari, G; Currier, JR; Harris, ME; Finkelstein, S; de Oliveira, A; Barkhan, D; Cox, JH; Zeira, M; Weinhold, KJ; Reinsmoen, N; McCutchan, F; Birx, DL; Osmanov, S; Maayan, S. HLA-A and -B allele expression and ability to develop anti-Gag cross-clade responses in subtype C HIV-1-infected Ethiopians. Human Immunology. 2004;65:648-659.  Abstract
  • Ferrari, G; Neal, W; Ottinger, J; Jones, AM; Edwards, BH; Goepfert, P; Betts, MR; Koup, RA; Buchbinder, S; McElrath, MJ; Tartaglia, J; Weinhold, KJ. Absence of immunodominant anti-Gag p17 (SL9) responses among Gag CTL-positive, HIV-uninfected vaccine recipients expressing the HLA-A*0201 allele. Journal of Immunology. 2004;173:2126-2133.  Abstract
  • Montefiori, DC; Metch, B; McElrath, MJ; Self, S; Weinhold, KJ; Corey, L; HIV Vaccine Trials Network. Demographic factors that influence the neutralizing antibody response in recipients of recombinant HIV-1 gp120 vaccines. Journal of Infectious Diseases. 2004;190:1962-1969.  Abstract
  • Wright, PF; Mestecky, J; McElrath, MJ; Keefer, MC; Gorse, GJ; Goepfert, PA; Moldoveanu, Z; Schwartz, D; Spearman, PW; El Habib, R; Spring, MD; Zhu, Y; Smith, C; Flores, J; Weinhold, KJ; National Institutes of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group. Comparison of systemic and mucosal delivery of 2 canarypox virus vaccines expressing either HIV-1 genes or the gene for rabies virus G protein. Journal of Infectious Diseases. 2004;189:1221-1231.  Abstract
  • Sufka, SA; Ferrari, G; Gryszowka, VE; Wrin, T; Fiscus, SA; Tomaras, GD; Staats, HF; Patel, DD; Sempowski, GD; Hellmann, NS; Weinhold, KJ; Hicks, CB. Prolonged CD4+ cell/virus load discordance during treatment with protease inhibitor-based highly active antiretroviral therapy: immune response and viral control. Journal of Infectious Diseases. 2003;187:1027-1037.  Abstract
  • Demarest, JF; Jack, N; Cleghorn, FR; Greenberg, ML; Hoffman, TL; Ottinger, JS; Fantry, L; Edwards, J; O'Brien, TR; Cao, K; Mahabir, B; Blattner, WA; Bartholomew, C; Weinhold, KJ. Immunologic and virologic analyses of an acutely HIV type 1-infected patient with extremely rapid disease progression. AIDS Research and Human Retroviruses. 2001;17:1333-1344.  Abstract