This laboratory takes an molecular immunologic approach
to problems of tumor pathology, with research directed
at understanding mechanisms of cancer development
as well as potential immunologic approaches to cancer
therapy. For example, we recently developed a genetically
modified allogeneic cellular vaccine directed against
a tumor-associated variant of the epidermal growth
factor receptor (EGFRvIII) which is effective in mice
against EGFRvIII-bearing tumors in both tumor protection
and treatment protocols. However, many immunotherapy
protocols which work in mice do not work well in human
cancer patients. These differences may be related
to changes in immune competence that occur with aging
of human cancer patients or to effects of tumors on
the immune system. T lymphocytes are thought to be
primarily responsible for anti-tumor cellular immune
responses. T cells mature in the thymus which is absolutely
necessary for initial development of a functional
T cell repertoire. However, the thymus has been observed
to atrophy with age, which may affect immune competence
when the pre-existing peripheral pool of T cells is
depleted, as occurs in patients with malignancies
requiring high dose chemotherapy or with HIV infection.
Our current studies aim to identify mechanisms regulating
the initiation and progression of thymic involution,
which will allow development of novel interventions
for immune reconstitution in these patients. In collaboration
with the Duke University Specialized Program of Research
Excellence (SPORE) in breast cancer, we are also investigating
structure-function relationships of the breast cancer
susceptibility gene product BRCA2.
