David C. Usher, Ph.D.

Teaching

*Course web site available through MyCourses

Research Interests

Our lab is interested in cholesterol homeostasis in adipocytes (fat cells). The regulation of cholesterol plays a major role in the production of fat droplets in these cells, where it is an essential component of the lipid droplets surface. Thus cholesterol may directly regulate the size of the adipocyte, which is an important factor in obesity. The focus our lab is on the control of cholesterol efflux and the control triglyceride synthesis by a purported transcription factor, SPOT14, which is itself indirectly sensitive to cholesterol levels.

We discovered that Apolipoprotein C-I (apoC-I) is highly up-regulated during the differentiation of both human and mouse adipocytes and that it is controlled by LXR, a transcription factor which is sensitive to a product of cholesterol synthesis. It is controlled in a manner which is similar to apolipoprotein E and the cholesterol transporter ABCA1. This suggests that apoC-I is involved in cholesterol efflux. In addition a second cholesterol transporter, ABCG1, was discovered to be synthesized by mouse but not human adipocytes upon differentiation. Our research is trying to determine the individual roles played by apoC-I, apoE, ABCA1 and ABCG1 in cholesterol efflux from adipocytes.

We are also investigating the function of SPOT14 in adipocytes. Like the cholesterol efflux genes, SPOT14 synthesis is sensitive to control by LXR. However, some of its purported liver target genes are not sensitive to SPOT14 regulation in adipocytes. In addition SPOT14 regulation of the purported genes is different in human and mouse adipocyte cell lines. We are in the process of determining which genes in the metabolism of glucose to triglycerides are regulated by SPOT14 in adipocytes.

Current Projects

  • Determining the role of apoC-I in cholesterol efflux. This project involves determining the fate of the apoC-I synthesized by adipocytes, which class of HDL has affinity for the secreted protein, and whether apoC-I itself interacts with either ABCA1 or ABCG1.
  • Determining factors which regulate apoC-I synthesis. This project involves the production of various promoter/reporter constructs and their stimulation or suppression by various factors.
  • Identifying genes which are sensitive to regulation by SPOT14 and then identifying elements in their promoters which are responsible for this regulation.

Research Group

  • William Cain, Ph.D. - Assistant Professor (Ph.D., University of Delaware). Catabolism of Lp(a).
  • Marysol Lavander, B.S. - Graduate Student (B.S., University of Delaware). The role of SPOT14 in the regulation of triglyceride production.
  • Aivi Nguyen - Undergraduate. The role of cholesterol efflux in adipocytes.

Selected Publications

Professor
Associate Chairperson

Phone: (302) 831-6685

Fax: (302) 831-2281

Email: dusher@udel.edu

Office: 223 McKinly Lab

Address:
Department of Biological Sciences
Wolf Hall
University of Delaware
Newark, DE 19716

Education

  • B.S. - University of California, Irvine
  • Ph.D. - University of Iowa
  • Postdoctoral - University of Illinois Medical Center