, a bio/informatics shared resource is still "open for business" - Visit the CDS website
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 an entirely new class of oncogenes: those
that govern 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.
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.
- Sandra Zinkel
Assistant Professor of Medicine
2220 Pierce Ave.
Nashville, TN 37232
No contact person provided
MeSH terms are retrieved from PubMed records. Learn more.
Key: MeSH Term KeywordAmino Acid Motifs apoptosis BCL-2 family BID biochemistry cancer Caspase 8 Caspase 9 cell cycle Cell Differentiation Cell Survival Chromatin DNA DNA-Binding Proteins DNA damage response DNA repair Encephalitis, Viral fas Receptor Fibroblasts knockout leukemia Leukemia, Myelomonocytic, Chronic Liver mass spectrometry Models, Biological Molecular Sequence Data mouse Myeloid Progenitor Cells Myeloproliferative Disorders phosphorylation Promoter Regions, Genetic proteomics Recombinant Proteins signal transduction S Phase stem cells