My laboratory focuses on mechanisms of cell death
in the immune system. Normally, cells require signals
from cytokines in their microenvironment to prevent
their spontaneous cell death. When lymphocytes are
deprived access to cytokines they undergo cellular
atrophy and become metabolically depressed prior to
their commitment to apoptosis via the pro-apoptotic
Bcl-2 proteins. If atrophy is prevented, however,
cell death can be attenuated, indicating that changes
in cell physiology contribute to the apoptotic sensitivity.
In contrast to the loss of metabolism that occurs
upon cytokine withdrawal, increased cellular metabolism
has been associated with cancer and may promote cancer
cell survival and growth. Understanding how cytokines
regulate cellular physiology and how alterations in
cell metabolism can affect cell growth and death are,
therefore, critical aspects in our understanding of
a wide variety of diseases, including cancer, autoimmunity,
immunodeficiency and degenerative diseases. To address
this issue my laboratory takes the dual approach of
analyzing cytokine signal transduction pathways that
regulate lymphocyte metabolism and to identify mechanisms
that regulate apoptosis by Bcl-2 family of proteins.
