Research Interests:

Arylamine N-acetyltransferases (NAT1 and NAT2) are traditionally known as phase II metabolic enzymes and express a well-defined genetic polymorphism in humans that modifies drug and xenobiotic metabolism. Recently, novel and interesting roles of NATs have emerged. NAT1, for instance, is frequently upregulated in breast cancer, and we and others have shown that it contributes to breast cancer growth and migration. As for NAT2, recent genome wide association studies have reported that genetic variants within the NAT2 gene are tightly linked to insulin resistance and high serum lipid level in humans, suggesting a previously unrecognized yet important role of NAT2 in development of metabolic disorders. In addition, we have recently discovered that NAT2 is transcriptionally regulated by glucose and insulin, and its tissue expression pattern coincides with those involved in lipid and cholesterol homeostasis. My laboratory works closely with Dr. David W. Hein (Dept. Pharm Tox) who is a leading expert in NAT biology. Together, we are currently investigating the novel cellular roles of NATs plus more, and these include: 1) Role of NAT1 in the de novo pyrimidine biosynthesis and maintaining mitochondrial integrity in breast cancer; 2) Transcriptional regulation of NAT2 and the role of NAT2 in lipid and cholesterol synthesis and transport; and 3) Mechanism of the bladder cancer risk allele (rs1495741), located downstream of NAT2. We are also interested in studying toxicants that contribute to metabolic disorders. We have recently found that heterocyclic amines, commonly present in cooked meat, can directly induce insulin resistance and increase glucose production in hepatocytes, and this effect is dependent on NAT2-mediated metabolism. The finding implies that exposure to heterocyclic amines through consumption of cooked meat may increase the risk of developing insulin resistance and hyperglycemia.

Publications:

For a complete list, please visit:   http://www.researcherid.com/rid/G-7145-2011