Dr. Simone Brixius-Anderko

Uuniversity of Pittsburgh
School of Pharmacy

Friday, March 8, 2024
12:00 Noon
Room 120 – Meyerhoff Chemistry Building
Host: Dr. Aaron Smith

“Of HEMEs and HETEs: Targeting fatty acid metabolizing enzymes for lung cancer treatment”

Lung cancer is the leading cause for cancer-related deaths worldwide with limited treatment options. Thus, new orthogonal treatment options are urgently needed. The cytochrome P450 4F11 (CYP4F11) is heavily upregulated in lung cancer patients. CYP4F11 catalyzes the w-hydroxylation of arachidonic acid yielding 20-hydroxyeicosatetraenoic acid (20-HETE). 20-HETE is a potent lipid mediator and regulates blood pressure and angiogenesis in healthy individuals. In cancer, 20-HETE signaling leads to cell proliferation and migration and tumor angiogenesis. The Brixius lab has recently shown that a transient knockdown of CYP4F11 in lung cancer cell lines dramatically attenuates cell proliferation and migration, thus, demonstrating the high potential of CYP4F11 as drug target. We use a combination of cell biology, biochemistry, and X-ray protein crystallography to reveal structure and function of CYP4F11 and accelerate its use as lung cancer drug target for transformative therapeutics.