Professor, Emeritus; Vice Chair, Pharmacology and Toxicology
Areas of Interest
Drug metabolism, phase 2 conjugation, sulfation, bile acid amidation, sulfotransferase
Biography
Graduated from University of South Florida in 1975 with a BA in Biology and the earned a MA in Zoology in 1978. In 1980 started the PhD program in Pharmacology at the University of Iowa under the mentorship of Thomas Tephly, MD/PhD. My dissertation research involved purification and characterization of three UDP-glucuronosyltransferases from rat liver. After graduation in 1984, I did an ACS post-doctoral fellowship with Dr Charles Kasper at the mcArdle Laboratory for Cancer Research at the Unv. of Madison-Wisconsin investigating the structure and regulation of the epoxide hydrolase gene.
In 1986 I accepted an Assistant Professor position in the Dept of Pharmacology at the Univ of Rochester. At Rochester I started a research program in the human cytosolic sulfotransferases in 1986 that has been funded by NIH ever since. Our laboratory has been been active in the molecular and biochemical characterization of the SULTs from human and laboratory species for over 30 years. In this period we have published over 125 research articles about the SULTs. In 1991 I accepted a position as an Associate Professor of Pharmacology at UAB and subsequently promoted to Professor with tenure.
Our laboratory has also investigated the molecular biology and biochemistry of the enzymes in bile acid amidation and the role of dimethylcyclosiloxanes in breast implants in the induction of cytochromes P450. Currently, lab laboratory is investigating the neuronal function of a highly conserved orphan SULT-like enzyme (SULT4A1) specifically localized in neurons in vertebrate brain. Our laboratory initially cloned this gene in 2000 and are characterizing it function in zebrafish, mouse and human brain.
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Research Interests
My research interests are focused on the characterization of the human cytosolic sulfotransferases and their role in endogenous and xenobiotic metabolism. Our lab has made many contributions to understanding the biochemistry and molecular biology of all members of the human SULT family and has been continuously funded by NIH in this area since 1986. We have published over 125 articles involving the SULTs.
Currently, we are investigating the regulation and function of a novel orphan member of the SULT gene family that my laboratory initially cloned and expressed in 2000. This isoform termed SULT4A1 is structurally related to the SULTs although no enzymatic activity has been identified. SULT4A1 is highly conserved throughout vertebrates and is selectively expressed in neurons in the brain. As shown SULT4A1 is partially associated with endoplasmic reticulum in cultured mouse neurons, a localization not seen with any other “cytosolic” SULTs.
Deletion of the SULT4A1 gene in mice results in visible tremor about post-natal day 7-8 with developing rigor, absence seizures, and failure to thrive with pups dying about weaning. This indicates a vital neural function for the SULT4A1 gene in vertebrates and suggests an association with 22q13 terminal deletion autistic syndromes.
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Selected Publications
Falany CN, and Tephly TR. Separation, purification and characterization of three isoforms of UDP-glucuronyltransferase from rat liver microsomes. Arch. Biochem. Biophys. 227: 248-258, 1983
Falany CN, McQuiddy P, and Kasper CB. Structure and organization of the gene for rat liver microsomal epoxide hydrolase. J. Biol. Chem. 262: 5924-5930, 1987.
Falany CN, Vazquez ME, and Kalb JM. Purification and characterization of human liver dehydroepiandrosterone sulfotransferase. Biochem. J. 260: 641-646, 1989.
Hirshey SJ, Dooley TP, Reardon IM, Heinrikson, and Falany CN. Sequence analysis, in vitro translation and expression of the cDNA for rat liver minoxidil sulfotransferase. Mol. Pharmacol. 42:257-264, 1992.
Wilborn TW, Comer KA, Dooley TP, Reardon IM, Heinrikson RL and Falany CN. Sequence Analysis and Expression of the cDNA for the Phenol Sulfating Form of Human Liver Phenol Sulfotransferase. Mol. Pharmacol. 263:70-77, 1993.
Falany CN, Xie X, Wang J, Ferrer J, and Falany JL. Molecular Cloning and Expression of Novel Sulfotransferase-Like cDNAs From Human and Rat Brain. Biochem. J.346:857-64, 2000.
He D, Wilborn TA, Li L and Falany CN. Repression of CFTR Activity in Human MMNK-1 Cholangiocytes Induces Sulfotranserase 1E1 Expression in Co-Cultured HepG2 Hepatocytes. Biochim. Biophys. Acta 1783 2391-2397, 2008.
Styles NA, Shonsey EM, Falany JL, Guidry AL, Barnes S and Falany CN. Carboxy-terminal mutations of bile acid CoA:N-acyltransferase alter activity and substrate specificity. J Lipid Research 57: 1133-43, 2016.
Crittenden F, Thomas HR, Parant JM and Falany CN. Activity Suppression Behavior Phenotype in SULT4A1 Frameshift Mutant Zebrafish, Drug Metab Disp 43:1037-1045, 2015.
Tibbs ZE and Falany CN. Dimeric human sulfotransferase 1B1 displays cofactor-dependent subunit communication. Pharmacol Res Perspect. 3, e00147, 2015.
Education
Ph.D., University of Iowa
Postdoctoral Fellowships
Postdoctoral Fellow, Univ of Wisconsin-Madison
Contact
Office Location
Volker Hall 151
Phone
205-934-9848
Email
cfalany@uab.edu