My main research interest is the study of enzymes involved in drug metabolism, in particular enzymes from the cytochrome P450 (P450) superfamily of enzymes.
My current research work with Dr. Sharon Murphy is focused on characterizing the human P450 enzymes involved in the metabolism of nicotine, the addictive agent in tobacco.
Nicotine is extensively metabolized in vivo, primarily by the hepatic enzyme P450 2A6. However; P450 2A13 which is expressed in the respiratory tract might contribute to nicotine metabolism in the lung. Recently we discovered that P450 2A6 and P450 2A13 are inactivated during nicotine metabolism. In addition, we have evidence suggesting that nicotine can undergo sequential metabolism where nicotine enters the active site of the enzyme and undergoes multiple oxidations prior to being released. We are currently investigating the mechanism of inactivation of these two enzymes by nicotine as well as characterizing the sequential metabolism.
von Weymarn Linda B; Chun Jamie A; Knudsen Gabriel A; Hollenberg Paul F. Effects of eleven isothiocyanates on P450 2A6- and 2A13-catalyzed coumarin 7-hydroxylation. Chemical research in toxicology 2007;20(9):1252-9.
von Weymarn Linda B; Chun Jamie A; Hollenberg Paul F. Effects of benzyl and phenethyl isothiocyanate on P450s 2A6 and 2A13: potential for chemoprevention in smokers. Carcinogenesis 2006;27(4):782-90.
von Weymarn Linda B; Zhang Qing-Yu; Ding Xinxin; Hollenberg Paul F. Effects of 8-methoxypsoralen on cytochrome P450 2A13. Carcinogenesis 2005;26(3):621-9.