Castle, J. David

J. David Castle

J. David Castle

Primary Appointment

Professor, Cell Biology

Education

  • BA, Biology, Carleton College, Northfield, MN
  • PhD, Cell Biology, Rockefeller University, New York, NY
  • Postdoc, Cell Biology, Yale Univ. Sch. of Med., New Haven, CT
  • Postdoc, Biophysical Chemistry, Univ. of California, Berkeley, CA

Contact Information

Jordan Hall, 3-111
Charlottesville, VA 22908
Telephone: 434-924-1786
Email: jdc4r@virginia.edu
Website: http://www.faculty.virginia.edu/castlelab/home.php

Research Interests

Regulation of Membrane Recycling and Protein Secretion

Research Description

The longstanding interest of my laboratory is on the regulation of membrane trafficking in the secretory and endocytic pathways. A new direction that is a major focus of our research concerns cholesterol regulation in insulin’s secretory pathway. Following upon collaborative studies (Sturek et al, 2010) that were conducted with Lynn Hedrick’s laboratory (now located at La Jolla Institute of Allergy and Immunology), we are examining how ATP binding cassette proteins ABCG1 and ABCA1 and other proteins that control intracellular cholesterol distribution collaborate to regulate the formation and function of insulin storage granules. It is now appreciated that phospholipid and cholesterol dynamics play major roles in regulating membrane trafficking during both secretion and endocytosis. This area is relatively underexplored even though there is growing appreciation that cholesterol dysregulation is a component of a broad spectrum of diseases - metabolic, neurodegenerative, and cancer. In our particular case, the ABC transporters being studied are significant to type-2 diabetes as their expression is altered in disease models and is required for endocrine pancreatic actions of selected antidiabetic drugs.

We also maintain an interest in the function of Secretory Carrier Membrane Proteins (SCAMPs), a family of proteins that were discovered in my laboratory. Our work has been focused along two lines: 1) deciphering the complementary roles of SCAMPs 1 and 2 in exo-endocytic coupling during secretion by neuroendocrine cells including those derived from adrenal medulla and endocrine pancreatic islets; and 2) analysis of the function of SCAMP3 in regulating endocytic sorting of epidermal growth factor receptor (EGFR).

Selected Publications