Christopher Wheeler, PhD
Research Scientist, Neurosurgery
|Maxine Dunitz Neurosurgical Institute|
|Associate Professor, Neurosurgery|
T cell-mediated protection and pathogenesis in age-related disease. Identify relevant cellular and molecular processes impacted by age in T cells, and test their contribution to disease courses by developing novel animal models and/or therapeutic clinical trials for age-related neurological diseases. Seek to elucidate the molecular nature of such T cell contribution to identify novel targets for immunotherapy against the most malignant brain tumors (glioblastoma multiforme), as well as against conditions such as Parkinson's and Alzheimer's disease.
Developed the functional definition of a heterodimeric CD8, a coreceptor on effector T cells, and defined the critical contribution of cells expressing this molecule to age-dependent clinical outcome in glioblastoma multiforme. Played a leadership role in developing the first successful program to treat glioblastoma multiforme patients with dendritic cell vaccination, including first determining that glioblastoma clinical outcomes improve in proportion to vaccine-induced immune responses, and determining that such responses sensitize brain tumors to chemotherapy. Clinical program is a leader in the brain tumor vaccine field.
Current investigations include:
T cell homing and function in normal and diseased brain. Immune models of neurodegeneration. Coreceptor glycosylation and self antigen responsiveness in aging T cells.
- Wheeler CJ, von Hoegen P, Parnes JR: An immunological role for the CD8 beta-chain. Nature, 357(6375): 247-9, 1992
- Wheeler CJ, Das A, Liu G, Yu JS, Black KL: Clinical responsiveness of glioblastoma multiforme to chemotherapy after vaccination. Clin. Cancer Res., 10(16): 5316-26, 2004
- Prins RM, Incardona F, Lau R, Lee P, Claus S, Zhang W, Black KL, Wheeler CJ: Characterization of defective CD4-CD8- T cells in murine tumors generated independent of antigen specificity. J. Immunol., 172(3): 1602-11, 2004
- Wheeler CJ, Black KL, Liu G, Mazer M, Zhang XX, Pepkowitz S, Goldfinger D, Ng H, Irvin D, Yu JS: Vaccination elicits correlated immune and clinical responses in glioblastoma multiforme patients. Cancer Res., 68(14): 5955-64, 2008
- Wheeler CJ, Maloney D, Fogel S, Goodenow RS: Microconversion between murine H-2 genes integrated into yeast. Nature, 347(6289): 192-4, 1990
- Wheeler CJ, Chen JY, Potter TA, Parnes JR: Mechanisms of CD8beta-mediated T cell response enhancement: interaction with MHC class I/beta2-microglobulin and functional coupling to TCR/CD3. J. Immunol., 160(9): 4199-207, 1998