Dr. Jonathan S. Bogan |
|
Yale University School of Medicine Internal Medicine Endocrinology Assistant Professor Yale University School of Medicine Cell Biology Assistant Professor |
Mailing AddressYale University School of Medicine Section of Endocrinology P.O. Box 208020 Department of Medicine New Haven, Connecticut 06520-8020United States | Contact Information |
Qualifications
M.D., Harvard University, Genetics, 1992.
B.S., Yale University, Electrical Engineering, 1986.
Expertise and Research Interests
Our work focuses on the molecular mechanisms by which insulin regulates glucose uptake and utilization in fat and muscle. The GLUT4 glucose transporter is expressed almost exclusively in these tissues, and the number and activity of these transporters at the cell surface controls the rate of glucose uptake. Insulin acts within minutes to redistribute GLUT4 glucose transporters from an intracellular location to the cell surface, thereby enhancing glucose uptake in a highly regulated manner. This action of insulin is defective in individuals with type 2 diabetes or pre-diabetic (insulin-resistant) physiology. Thus, a detailed knowledge of how insulin controls GLUT4 trafficking is essential to a full understanding of the defects underlying type 2 diabetes.
Control of GLUT4 trafficking is also of significant interest as a fundamental problem in cell biology. Unlike proteins that recycle constitutively at the plasma membrane, GLUT4 is efficiently retained within cells in the absence of insulin. The mechanisms for this retention are unclear, and GLUT4 appears to be targeted to a post-endosomal compartment that remains poorly defined. The major effect of insulin is to mobilize this pool of retained GLUT4 to the plasma membrane. Similar mechanisms may control other transporters that recycle at the plasma membrane in a homonally regulated manner.
We developed a novel and efficient functional strategy to identify proteins through which insulin regulates GLUT4 trafficking. This method relies on flow cytometry to enrich for cells stably expressing particular proteins, within an adipocyte cDNA library, that alter the proportion of GLUT4 at the plasma membrane. Using this technique we identified at least one novel protein, TUG, that controls GLUT4 trafficking, and linking hormonal regulation of GLUT4 to the action of ubiquitin-like proteins. Current work focuses on elucidating the detailed mechanism by which this protein functions. Additional projects will examine the role of this protein in organism-level physiology.
Control of GLUT4 trafficking is also of significant interest as a fundamental problem in cell biology. Unlike proteins that recycle constitutively at the plasma membrane, GLUT4 is efficiently retained within cells in the absence of insulin. The mechanisms for this retention are unclear, and GLUT4 appears to be targeted to a post-endosomal compartment that remains poorly defined. The major effect of insulin is to mobilize this pool of retained GLUT4 to the plasma membrane. Similar mechanisms may control other transporters that recycle at the plasma membrane in a homonally regulated manner.
We developed a novel and efficient functional strategy to identify proteins through which insulin regulates GLUT4 trafficking. This method relies on flow cytometry to enrich for cells stably expressing particular proteins, within an adipocyte cDNA library, that alter the proportion of GLUT4 at the plasma membrane. Using this technique we identified at least one novel protein, TUG, that controls GLUT4 trafficking, and linking hormonal regulation of GLUT4 to the action of ubiquitin-like proteins. Current work focuses on elucidating the detailed mechanism by which this protein functions. Additional projects will examine the role of this protein in organism-level physiology.
Other Expertise
I wish to be contacted by interested students (medical, graduate, or undergraduate) and postdoctorals as a potential research advisor.
Keywords
COS Keywords:
Cell Biology, Confocal Microscopy, Diabetes, Digestive Diseases and Disorders, Digestive System, Electrical Engineering or Electronics, Endocrinology, Flow Cytometry, Fluorescence, Genetics, Higher Education, Insulin, Internal Medicine, Kidney (Renal) Functions, Kidney Disease, Laboratory Animal Science, Medical Education, Membranes, Metabolism, Microscopy, Signal Transduction, Urology.Additional Terms:
Adipocyte, Biological Signal Transduction, Cell Membrane, Confocal Scanning Microscopy, Fluorescence Microscopy, Glucose Transporter, Hormone Regulation Control Mechanism, Insulin, Insulin Receptor, Laboratory Mouse, Receptor Binding, Secretion, Vesicle Vacuole.Memberships
American Association for the Advancement of Science
American College of Physicians
American Diabetes Association
American Society for Biochemistry and Molecular Biology
American Society for Cell Biology
Massachusetts Medical Society
Honors and Awards
2006, Distinguished Young Scholar in Medical Research,
W. M. Keck Foundation
1993, Research Award for Clinical Trainees,
NIH Office of Education
1992, M.D. degree summa cum laude,
1992, Leon Resnick Memorial Prize for excellence and accomplishment in research,
Harvard Medical School
1986, B.S. degree cum laude,
1986, Jim Clarke Prize for excellence in Electrical Engineering,
Yale College
1986, Sigma Xi
Previous Positions
2001-2002, Assistant Professor,
Harvard University,
Medical School,
Medicine,
Diabetes Unit, Massachusetts General Hospital
1998-2001, Instructor,
Harvard University,
Medical School,
Medicine,
Diabetes Unit, Massachusetts General Hospital
1994-1998, Clinical and Research Fellow,
Massachusetts General Hospital,
Harvard Medical School,
Endocrine Division
1992-1994, Intern and Resident,
Massachusetts General Hospital,
Medicine
Patents
TUG, a regulator of GLUT4 trafficking,
Patent Number: pending,
2003,
Institution-owned,
United States.
Method of Measuring Plasma Membrane Targeting of GLUT4,
Patent Number: 6632924,
2003,
Institution-owned,
United States.
Expression cloning method,
Patent Number: pending,
2002,
Institution-owned,
United States.
Method of Measuring Plasma Membrane Targeting of GLUT4,
Patent Number: 6303373,
2001,
Institution-owned,
United States.
Funding Received
- American Diabetes Association: Career Development Award, Jul 2000 to Jun 2004.
- Chestnut Hill Charitable Foundation: New Investigator Award, Jul 2000 to Jun 2002.
- National Institutes of Health (NIH): Physician Scientist Award, Jul 1995 to Jun 2000.
- National Institutes of Health (NIH): Functional cloning of proteins used in GLUT4 trafficking, Jan 2000 to Dec 2003.
- National Institutes of Health (NIH): Insulin stimulated ubiquitin-like modification, 2007 to 2012.
- W. M. Keck Foundation: Distinguished Young Scholar in Medical Research, 2006 to 2011.
- National Institutes of Health (NIH): Proteomic characterization of insulin signaling targets, 2005 to 2007.
- American Diabetes Association (ADA): Regulation of glucose transporter trafficking, 2005 to 2007.
- HHMI-Yale Center for Human Genetics and Genomics: New Faculty Start-up Grant, 2004 to 2005.
Publications
- Yu, C., Cresswell, J., Löffler, M.G., Bogan, J.S. (2007) The Glucose Transporter 4-regulating Protein TUG Is Essential for Highly Insulin-responsive Glucose Uptake in 3T3-L1 Adipocytes, Journal of Biological Chemistry, 282 (10), 7710-22
- Tettamanzi, M.C., Yu, C., Bogan, J.S., Hodsdon, M.E. (2006) Solution structure and backbone dynamics of an N-terminal ubiquitin-like domain in the GLUT4-regulating protein, TUG, Protein Science, 15 (3), 498-508
- Hug C, Wang J, Ahmad NS, Bogan JS, Tsao TS, Lodish HF, T-cadherin is a receptor for hexameric and high-molecular-weight forms of
Acrp30/adiponectin, Proceedings of the National Academy of Sciences of the United States of America., 101(28), 10308-13, July 2004
- Bogan JS, Hendon N, McKee AE, Tsao TS, Lodish HF, Functional cloning of TUG as a regulator of GLUT4 glucose transporter
trafficking, Nature, 425(6959), 727-33, October 2003
- Bogan JS, McKee AE, Lodish HF, Insulin-responsive compartments containing GLUT4 in 3T3-L1 and CHO cells:
regulation by amino acid concentrations, Molecular and Cellular Biology, 21(14), 4785-806, July 2001
- Liu X, Constantinescu SN, Sun Y, Bogan JS, Hirsch D, Weinberg RA, Lodish HF, Generation of mammalian cells stably expressing multiple genes at
predetermined levels, Analytical Biochemistry, 280(1), 20-8, April 2000
- Bogan JS, Lodish HF, Two compartments for insulin-stimulated exocytosis in 3T3-L1 adipocytes
defined by endogenous ACRP30 and GLUT4, Journal of Cell Biology, 146(3), 609-20, August 1999
- Katznelson L, Bogan JS, Trob JR, Schoenfeld DA, Hedley-Whyte ET, Hsu DW, Zervas NT, Swearingen B, Sleeper M, Klibanski A, Biochemical assessment of Cushing's disease in patients with corticotroph
macroadenomas, Journal of Clinical Endocrinology and Metabolism, 83(5), 1619-23, May 1998
- Bogan JS, Page DC, Ovary? Testis?--A mammalian dilemma, Cell, 76(4), 603-7, February 1994
- Behlke MA, Bogan JS, Beer-Romero P, Page DC, Evidence that the SRY protein is encoded by a single exon on the human Y
chromosome, Genomics, 17(3), 736-9, September 1993
- Vollrath D, Foote S, Hilton A, Brown LG, Beer-Romero P, Bogan JS, Page DC, The human Y chromosome: a 43-interval map based on naturally occurring
deletions, Science, 258(5079), 52-9, October 1992
- Cantrell MA, Bogan JS, Simpson E, Bicknell JN, Goulmy E, Chandler P, Pagon RA, Walker DC, Thuline HC, Graham JM Jr, et al., Deletion mapping of H-Y antigen to the long arm of the human Y chromosome, Genomics, 13(4), 1255-60, August 1992
- Bogan, J.S., and Jue T., A Computer-Controlled Attenuator for Indirect Detection Experiments, Journal of Magnetic Resonance, 70, 140-143, 1986
Profile Details
Last Updated: 4/19/2007
COS Expertise ID #531359
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