Medical Student Research Fellowship for Summer 2007

Mentor: Jonathan Cohen
Department: Center for Human Nutrition
Room number: Y3-212
Mail Code: 9052
Phone number: 8-4774
E-mail: jonathan.cohen@utsouthwestern.edu
Project title: Mechanism of Action of PCSK9

Human subjects IRB approved project number (where applicable): NA

Animal subjects IRB approved project number (where applicable): NA

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects) BASIC

Brief Description of Project:

The goal of this project is to identify the sequences in PCSK9 that are required to promote degradation of the low density lipoprotein receptor (LDLR). We will use site directed mutagenesis to generate mutations in PCSK9 that alter specific amino acids in regions predicted to be required for function. The PCSK9 expression constructs will then be assayed for their ability to promote degradation of LDLRs in cultured cells.

Previous Research Activities or Publications with Medical Students:

Yang C, McDonald JG, Patel A, Zhang Y, Umetani M, Xu F, Westover EJ, Covey DF, Mangelsdorf DJ, Cohen JC, Hobbs HH. Sterol intermediates from cholesterol biosynthetic pathway as liver X receptor ligands. J Biol Chem. 2006 Sep 22;281(38):27816-26.

Moschetta A, Xu F, Hagey LR, van Berge-Henegouwen GP, van Erpecum KJ, Brouwers JF, Cohen JC, Bierman M, Hobbs HH, Steinbach JH, Hofmann AF. A phylogenetic survey of biliary lipids in vertebrates. J Lipid Res. 2005 Oct;46(10):2221-32.

Cohen J, Pertsemlidis A, Kotowski IK, Graham R, Garcia CK, Hobbs HH. Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat Genet. 2005 Feb;37(2):161-5.

Yu L, Gupta S, Xu F, Liverman AD, Moschetta A, Mangelsdorf DJ, Repa JJ, Hobbs HH, Cohen JC. Expression of ABCG5 and ABCG8 is required for regulation of biliary cholesterol secretion. J Biol Chem. 2005 Mar 11;280(10):8742-7.