Professor and Vice Chief

Division of Surgical Sciences

Department of Surgery

Duke University Medical Center

204 Surgical Oncology Research Facility (SORF)

Durham, NC  27710

919-684-5572

 

The laboratory of Kent J. Weinhold, PhD is actively engaged in comprehensive research efforts characterizing cellular immune reactivities present in HIV-1 infected patients, non-infected recipients of candidate AIDS vaccines and patients with selected solid tumors or emerging infections.  The overall goal of these studies is the development of innovative immune therapeutic approaches that are based on extensive pre-clinical analyses of relevant anti-viral and anti-tumor cytotoxic T-lymphocyte (CTL) reactivities.  In addition, the laboratory recently began comprehensive studies to map T-cell epitopes in poxviruses, Ebola virus, and multi-drug resistant Mycobacterium tuberculosis. In the field of AIDS research, Dr. Weinhold is conducting NIAID/NIH sponsored studies aimed at characterizing CD4 and CD8 T-cell specificities and frequencies present in HIV-infected patients, with particular emphasis on early events which take place during the acute phase of the disease.  Additionally, ongoing studies of CTL reactivities present in so-called 'long-term non-progressors' versus 'rapid progressors' are being conducted in efforts to identify the correlates of immune protection that are operative during HIV-1 infection. 

In the field of tumor immunology, Dr. Weinhold is conducting research examining the CTL responses present in patients with metastatic breast cancer, malignant melanoma, and pancreatic carcinomas, focusing on responses against highly-conserved TAA such as CEA, HER2/neu, p53, MAGE and k-ras encoded determinants mediated by central and effector memory T-cell populations within tumor-infiltrating lymphocytes (TIL), malignant effusions, and peripheral blood mononuclear cells.

 

 

Most recently, the Weinhold laboratory has been utilizing several novel strategies to map and validate MHC class I-restricted epitopes in potential agents of biowarfare as well as agents responsible for emerging infections, with the ultimate goal of utilizing these epitopes as components f future vaccine strategies.



In his capacity as Director of the Surgical Virology Laboratory at Duke, Dr. Weinhold oversees the comprehensive immunologic monitoring efforts of several NIH-supported initiatives.  He is presently Principal Investigator of the NIH-sponsored HIV Vaccine Trials Network (HVTN) Duke Immune Monitoring Laboratory responsible for measuring HIV-specific immune responses elicited in response to candidate AIDS vaccines undergoing Phase I/II testing.  All aspects of immunologic testing in conjunction with HVTN clinical trials are performed under strict compliance with Good Clinical Laboratory Practices (GCLP) guidelines.  All assays are performed according to formally validated Standard Operating Procedures (SOP) and the laboratory maintains certification through participation in regular proficiency testing under the direct supervision of the NIH.  Dr. Weinhold also serves as Director of the Immune Monitoring Core of the Center for HIV/AIDS Vaccine Immunology (CHAVI) recently awarded to Dr. Barton Haynes at Duke.  In this capacity, Dr. Weinhold is charged with development of novel assay strategies to be used in determining the ‘correlates of immune protection’ against HIV-1 infection in conjunction with ongoing CHAVI discovery protocols.  Any new assay strategies that are used as immunologic endpoints in these studies undergo formal validation in accordance with GCLP guidelines.  With regard to measurement of cellular reactivities, these efforts are clearly focused on the development and continual refinement of flow cytometry-based readouts, especially polychromatic flow cytometry aimed at assessing functional reactivities (eg. intracellular cytokine staining (ICS), degranulation, etc.) within phenotypically-defined central and effector memory T cell populations.

Lastly, Dr. Weinhold is Director of the Duke Center for AIDS Research (CFAR) as well as Director of the CFAR Flow Cytometry Core.  In this latter capacity, he is responsible for providing state-of-the-art flow cytometry and cell sorting technologies to the community of AIDS and non-AIDS investigators at Duke.  As there is significant technologic ‘cross talk’ between AIDS-related and non-AIDS-related studies, many of the strategies developed for one type of study can be readily adapted for another.  As an example, the 12-color assay developed as a means of assessing HIV-specific cellular responses in vaccine recipients as well as HIV-infected patients, serves as the framework for assessment of polyfunctional reactivities against CMV and other human viral pathogens.