Molecular mechanisms to regulate apoptotic pathways in normal and malignant cells.
B.S., Indiana University
Ph.D., Yale University
M.D., University of Chicago
My lab is interested in understanding the mechanisms by which normal and malignant cells regulate programmed cell death or apoptosis following DNA damage. Multicellular organisms have devised a tightly regulated, genetically programmed mechanism of cell suicide to maintain homeostasis and to prevent propagation of genetically damaged cells. The discovery of the BCL-2 family of genes uncovered the underlying genetic mechanism of this regulation, as well as a class of oncogenes that governs cell death rather than cell proliferation.
Current studies focus on the pro-death BCL-2 family member BID. The deletion of BID in mice prolongs the lives of myeloid cells culminating in the development of a fatal disorder resembling the human disease chronic myelomonocytic leukemia (CMML). Our recent work has shown an additional role for BID in preserving genomic integrity that is distinct from its pro-apoptotic role. Following DNA damage, BID is phosphorylated by the DNA damage kinase ATM and plays a role in cell cycle checkpoint control. Cells initiate a complex series of responses subsequent to DNA damage including activation of cell cycle checkpoints, promoting DNA repair, or activating apoptosis. BID, with its dual function in apoptosis and the DNA damage response, is well situated to serve as a mediator in determining cell fate following DNA damage.
An additional focus of the lab is on the role of the Bcl-2 family of proteins in hematopoietic differentiation and stem cell function.
The projects in my lab use hematopoietic cell culture systems, mouse models, immunofluorescence, as well as apoptosis, cell cycle checkpoint and DNA repair assays to understand the signals and protein interactions that direct BID to assume an apoptotic or cell cycle checkpoint/DNA repair role following treatment with agents inducing DNA damage. An additional focus is to dissect the mechanism of Bcl-2 family members in mouse models of leukemia. Our studies provide new insights into the interplay between apoptosis and cell cycle checkpoint/DNA repair responses following DNA damage, and their role in myeloid homeostasis and leukemogenesis.
Postdoctoral Positions Available
I have an opening for a highly motivated post-doctoral fellow with a strong record of productivity. My laboratory studies the role of BCL-2 family members in cell cycle control, DNA repair and apoptosis following DNA damage (Zinkel et al., Cell 122:579-591(2005). Zinkel et al., Genes & Dev. 17:229-239 (2003).) We utilize molecular, cellular and biochemical approaches as well as mouse models to investigate the role of the pro-apoptotic family member BID in the DNA damage response and leukemogenesis.
Interested applicants should send a cover letter along with a curriculum vita and the names of three to five references to: email@example.com.