Daniel J. Noonan, Ph.D.
Assistant Professor

Department of Biochemistry

Phone:
(859) 257-7498

Fax:
(859) 323-1037

e-mail:
dnoonan@ukcc.uky.edu

Peroxisomes are subcellular organelles that are involved in a variety of metabolic processes. The proliferation of and the activities within peroxisomes appear to be directly effected by a variety of chemicals including antihyperlipidemic drugs and rodent hepatocarcinogens. My group has isolated and is characterizing a small family of intracellular receptors ( peroxisome proliferator-activated receptors: PPAR) that can be activated by peroxisome proliferators. Once activated these receptors function as transcription factors and appear to be intimately involved in the regulation of fat breakdown, synthesis and storage. Furthermore, abnormal regulation of one of these receptors (PPARa ) has been directly implicated in the development of rodent liver cancer. We have recently linked activation of this receptor to another member of the steroid receptor superfamily of genes (farnesoid X-activated receptor: FXR), and this linkage provides for a provocative hypothetical mechanism for PPAR-associated rodent hepatocarcinogenesis (see references below). A major direction of the research in my laboratory is in establishing the validity of this hypothesis. A variety of "state of the art" molecular biology techniques are being used to identify and characterize genes regulated by these receptors. It is hoped that this information will elucidate a basic mechanism by which conditions such as obesity, and xenobiotics such as environmental toxins, might create and promote the development of cancer.

Research Publications/Presentations

O’Brien ML, SM Rangwala, KW Henry, C Weinberger, DC Crick, CJ Waechter, DR Feller and DJ Noonan. Convergence of three steroid receptor pathways in mediation of nongenotoxic hepatocarcinogenesis. Carcinogenesis 17:185-190, 1996.

Forman, BM, E Goode, AE Oro, D Bradley, T Perlmann, T Burka, T McMorris, C Kozak, WW Lamph, DJ Noonan, RM Evans, and C Weinberger. A nuclear receptor identifying a signaling pathway for farnesol metabolites, Cell 81:687-693, 1995.

Henry, K, ML O’Brien, W Clevenger, L Jow and DJ Noonan. Peroxisome Proliferator-Activated Receptor Response Specificities As Defined in Yeast and Mammalian Cell Transcription Assays. Toxcol. Appl. Pharmacol. 132:317-324, 1995.

Espandiari P, VA Thomas, HP Glauert, O’Brien, DJ Noonan and LW Robertson. The herbicide dicamba (2-methoxy-3, 6-dichlorobenzoic acid) is a peroxisome proliferator in rats. Fundam. Appl. Toxicol. 26:85-90, 1995.

Rangwalla S, ML O’Brien, V Tortorella, F Loiodice, D Noonan and DR Feller. Stereoselective effects of chiral clofibric acid analogs on rat peroxisome proliferator-activated receptor a (rPPARa ) activation and peroxisomal fatty acid b -oxidation. Chirality (in press) 1996.

Noonan DJ and ML O’Brien. (1996) A Hypothetical Mechanism for Fat Induced Rodent Hepatocarcinogenesis. In: Dietary Fat and Cancer: Genetic and Molecular Interactions. ed. JP Cohn. Plenum Press (in press) 1996.