Heather

M

Lamb

,

PhD

BCL-2 family members are regulators of programmed cell death and appear to have causal roles in several human cancers. The activities of BCL-2 proteins during the final minutes in a cell’s life are the focus of intense effort to understand the underlying molecular details. However, the functions of BCL-2 proteins in healthy cells are seldom investigated, despite increasing evidence that they have distinct “day jobs” that are crucial for normal cellular processes. For example, we have shown that the pro-survival BCL-2 family member, BCL-xL, regulates mitochondrial morphology, homeostasis, and synaptic activity in neurons, which we believe may influence the initial steps in neurodegeneration. The molecular mechanism underlying this function is unknown, but is suggested to be a more evolutionarily conserved function of BCL-2 proteins compared to their roles in regulating programmed cell death.



Cellular BCL-2 homologues are also predicted to alter membrane curvature, and our laboratory has demonstrated that BCL-xL and the related pro-death family member, Bax, can directly promote positive curvature of synthetic liposome membranes. During my postdoctoral training in Dr. J. Marie Hardwick’s laboratory, I developed a novel cell-based assay for examining the membrane shaping properties of BCL-2 proteins using the endoplasmic reticulum as a model membrane. By defining the curvature-promoting properties of BCL-2 family members in the ER, I provide further evidence that support the hypothesis that BCL-xL and Bax influence mitochondrial dynamics by directly manipulating lipid membranes. Other current efforts relate to understanding novel functions of the BCL-2 family members, BID and BCL2L12.



Beyond my research efforts, I have initiated an effort to organize the non-tenure track (NTT) faculty within our department with the objectives of: 1) Building a community of colleagues that fosters collaboration, exchange of resources and expertise, and camaraderie; 2) Enhance professional and research goals through the development of a peer mentoring system, writing accountability groups, and opportunities for NTT faculty to present their research; 3) Work with administration at the department and school level to better outline pathways to promotion (within the NTT track), as well as develop a formal recognition system for teaching and mentoring efforts in the laboratory; and 4) Expand our network to include NTT faculty members from other basic science departments across SPH and SOM.