Venezia by PVII

Austin J. Cooney, Ph.D.

Assistant Professor of Molecular and Cellular Biology
Baylor College of Medicine
acooney@bcm.tmc.edu

Regulation of Differentiation, Development and Homeostatic Processes by Members of the Nuclear Super Family of Ligand-Activated Transcription Factors

My primary research interest is the regulation of differentiation, development and homeostatic processes by members of the nuclear super family of ligand-activated transcription factors.  The primary nuclear receptors of interest are the orphan receptors, which have no known ligands/hormones and only poorly understood physiological functions.  One such orphan nuclear receptor of particular interest in HNF4 (Hepatic Nuclear Factor4).  This orphan receptor is expressed in the liver, intestine and pancreatic ¥ cells suggesting that it is involved in the regulation of metabolic processes.  In addition, mutations in the human HNF4 gene have been associated with Maturity Onset Diabetes of the Young (MODY1), a type of non-insulin-dependent diabetes mellitus.  This implicates HNF4 in the regulation of glucose homeostasis.

HNF4 has been studied by targeted mouse genetics; however, knockout of the HNF4 gene leads to embryonic lethality, showing that it plays an important non-redundant role in embryonic lethality.  Embryonic lethality, however, prevents the study of the role of this orphan receptor in the adult.  To overcome this problem, studies are planned to inactivate the HNF4 gene in the adult using the Cre/Lox system.  This type of strategy allows systematic inactivation of the HNF4 gene in the liver, intestine and pancreatic ¥ cells and will permit studies of the physiological role of this receptor in maintaining glucose homeostasis and the regulation of metabolism.

Representative publications:

Cooney AJ.  Use of DNA polymerase to create cohesive termini in PCR products.  Biotechniques 1997; 24:30-34.

Agoulnik IY, Cho Y, Niederberer C, Kieback DG, and Cooney AJ.  Cloning, expression analysis and chromosomal localization of the human nuclear receptor gene GCNF. FEBS Lett 1998; 424:73-78.

Cooney AJ, Hummelke GC, Herman T, Chen F, and Jackson KJ.  Germ Cell Nuclear Factor a response element-specific repressor of transcription.  Biochem Biophys Res Commun 1998; 245:94-100.

Hummelke GC, Meistrich M and Cooney AJ.  The mouse protamine genes are candidate targets for the novel orphan nuclear receptor, Germ Cell Nuclear Factor.  Mol Repro Dev 1998; 50:396-405.

Cooney AJ, Tsai SY and Tsai M-J.  In vitro transcription and characterization of transcription.  In: Transcription Factors: A Practical Approach.  Latchman (ed), IRL Press, Oxford 1999, 63-96.

Cooney AJ.  Germ Cell Nuclear Factor: an orphan receptor in search of a function. Am Zoologist 1999 (in press)