Biochemistry

Department of Biochemistry

Departmental Focus

The members of the Department of Biochemistry study the biochemical events that regulate cell growth and differentiation and that are associated with transformation when genes are altered. One common theme with the department is the signal transduction pathways and mechanisms that regulate the life or death of cells through control of apoptosis, particularly hematopoietic cells. Several groups work on members of the Bcl-2 family of proteins that function to either protect cells from apoptosis or are responsible for inducing apoptosis. For example, studies have demonstrated an essential role for the mitochondrial protein, Mcl-1, in survival from apoptosis of a variety of cells including all lineages of hematopoietic cells. Current studies are focused on how the protein is regulated, particularly by cytokines, and how it functions to protect cells from the onset of apoptosis. Another group has focused on the mitochondrial protein Hax1, which is a distant member of the Bcl-2 family of proteins. Loss of Hax1 results in increased apoptosis and concomitant loss of both hematopoietic cells and neurons. In children, others have shown that loss of Hax1 is responsible for one form of congenital neutropenia due to increased apoptosis of granulocytes. Recent studies, collaborative between departmental groups, have shown that the critical function of Hax1 in the mitochondria is to form a complex with a mitochondrial protease termed Parl on the inner mitochondrial membrane. In the complex, Hax1 is responsible for binding to another mitochondrial protease termed HtrA2 in a manner in which Parl can cleave a region of HtrA2 to allow it to become an active protease in the inter mitochondrial membrane space. The studies further identified a potential substrate for HtrA2; namely, the Bcl-2 family member Bax which is responsible for causing mitochondrial damage and subsequent activation of the apoptotic pathways. Studies among the groups are further focusing on establishing the mechanisms by which cells regulate both for and against apoptosis.


Contact Us

Biochemistry
MS 340, Room D4007D
St. Jude Children's Research Hospital
262 Danny Thomas Place
Memphis, TN 38105-3678

Phone: (901) 595-3420
FAX: (901) 525-8025


Faculty

Michael M. Meagher, PhD  Recombinant protein expression, purification and scale-up

Leta K. Nutt, PhD  Metabolic regulation of cancer cell death

Janet F. Partridge, PhD  Chromosome segregation, heterochromatin assembly

Gerard P. Zambetti, PhD  p53 function in tumor suppression & tumorigenesis