August 27, 2009
Craig Lee, PharmD, PhD, an assistant professor at the UNC Eshelman School of Pharmacy, has received a grant from the National Institutes of Health for a study that could lead to more treatment options for inflammation.
The grant, worth up to $1.55 million over five years, will fund research investigating the role of a family of enzymes called cytochromes P450 — CYP for short — in the regulation of inflammatory responses in the liver and other tissues.
“Inflammation plays an integral role in the development of numerous diseases and conditions, such as cardiovascular disease, asthma, cancer, and septic shock,” says Lee, a faculty member in the Division of Pharmacotherapy and Experimental Therapeutics. “Finding new ways to inhibit inflammation will open up substantial therapeutic possibilities for these diseases.”
Inflammation is controlled by signaling molecules called eicosanoids, which are metabolized by various enzyme pathways. Some existing anti-inflammatory therapies, such as aspirins and other NSAIDs, were derived from studies of the cyclooxygenase pathway that produces the prostaglandin class of eicosanoids. However, these therapies do not work for everyone.
Lee believes that studying the CYP pathways, which produce a parallel class of eicosanoids, could reveal new ways to inhibit inflammation. His project will use genetic and pharmacological approaches to study the role of CYP-mediated eicosanoid metabolism in regulating inflammation in mice, as well as the underlying mechanisms.
The study will focus on two CYP pathways — CYP epoxygenase and CYP ω-hydroxylase. CYP epoxygenases produce EETs, an eicosanoid that inhibits inflammation, while CYP ω-hydroxylases produce 20-HETE, an eicosanoid that causes inflammation.
“We believe that by obtaining higher levels of EETs and lower levels of 20-HETE, we can inhibit inflammation in the liver and elsewhere in the body, which can potentially be a new way to treat diseases where inflammation is important,” Lee says.
Lee says this can be accomplished in three ways: stimulating the CYP epoxygenase pathway to boost EET production, inhibiting EET clearance to retain more EETs, and inhibiting the CYP ω-hydroxylase pathway to lower the production of 20-HETE.
“We also believe that combining these approaches may have the greatest anti-inflammatory effect,” he says.
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