Patricia Brubaker, PhD.
Dr. Brubaker Contact Information:
Phone: (416) 978-2593 (office)
Phone 2: (416) 978-1954 (lab)
Fax: (416) 978-4373
Email: p.brubaker@utoronto.ca
Webpage: EDRG
Canada Research Chair
Address: Department of Physiology, Medical Sciences Building, Rm. 3366, University of Toronto, 1 King's College Circle, Toronto, ON Canada M5S 1A8

ACADEMIC STATUS
Departmental Status: Full Professor and Associate Chair, Academic

Primary/Cross-appointments: Medicine

Degrees: Ph.D 1982

Affiliations: Canada Research Chair in Vascular and Metabolic Biology

Courses Taught: PSL304H and PSL305H

RESEARCH
Research Division: Endocrine and Diabetes Platform

Research Interests: Tissue-specific synthesis, secretion and biological activities of intestinal and pancreatic endocrine hormones, with a particular focus on the proglucagon-derived peptides, glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2).

Keywords: Intestine/ Pancreas/ Brain/ Peptide Hormones/ Growth Factors/ Diabetes/ Intestinal disease

Detailed Description: The major interest of my laboratory is the factors that determine tissue-specific synthesis, secretion and bioactivities of regulatory peptides. In particular, we have focussed on a family of peptides that are produced in the intestine, pancreas and brain, the proglucagon-derived peptides that are encoded by the proglucagon gene.

Proglucagon encodes the sequence of at least 9 distinct peptides, including glucagon, and the glucagon-like peptides, GLP-1 and GLP-2. The physiological role of pancreatic glucagon as a stimulator of hepatic glucose production has been known for over 70 years. In contrast, the biological functions of the intestinal proglucagon-derived peptides, GLP-1 and GLP-2, have only been elucidated over the past two decades.

In 1987, it was first established that GLP-1 is a potent stimulator of glucose-dependent insulin secretion. Since then, GLP-1 has also been demonstrated to inhibit glucagon release, gastric emptying and appetite. Furthermore, more recent studies have shown that GLP-1 induces pancreatic beta-cell growth, suggesting that it may play a role in the regeneration of pancreatic islets. Because of its pleiotrophic effects to reduce blood sugar levels, GLP-1 receptor agonists and GLP-1 degradation inhibitors have recently been approved as novel treatments for patients with Type II diabetes.

The function of GLP-2 as a stimulator of intestinal growth and function was first demonstrated by Drucker and Brubaker in 1996. The importance of this peptide to intestinal health in both physiology and disease has now been so convincingly demonstrated that FDA approval is currently pending for the use of a long-acting GLP-2 analog in patients with Short Bowel Syndrome; phase II trials for patients with Crohn’s disease are also underway.

As a model for studies on the tissue-specific production of regulatory peptides, the proglucagon-derived peptides represent a novel and physiologically important family of hormones. My laboratory utilizes a wide-variety of approaches to investigate the synthesis, secretion and biological activities of these peptides, including in vitro primary and tumour cell cultures, normal and genetically-manipulated animal models, immunohistochemistry, high performance liquid chromatography, western blot, RT-PCR and real-time PCR.

METHODS USED
Cell and tissue cultures: pancreas cells, intestinal cells.

Procedures: Adenovirus, HPLC, gene expression analysis, glucose clamp, immunohistochemistry, immunocytochemistry, intestinal perfusions, ITT, OGTT, qRT-PCR, RIA, RT-PCR, siRNA, vagotomy, western blot.

EQUIPMENT USED
Blotting apparatus, culture hood, culture incubators, deconvolution fluorescence microscope, departmental beta and gamma counters, gel apparatus, HPLC, infusion apparatus, IVIS whole animal imager low- and high-speed centrifuge, plate reader (MSD), real-time/thermocycler.

SAMPLE PUBLICATIONS AND ABSTRACTS
Click on Link to PubMed

PRESENT TRAINEES
Jasleen Chahal
Charlotte Dong
Samantha Li
Dr. Manuel Gil-Lozano

PRESENT COLLABORATIONS
Within the Department of Physiology:
Steffen Bolz
Scott Heximer

Outside the Department of Physiology:
Khosrow Adeli, University of Toronto
Richard Bazinet, University of Toronto
Daniel Drucker, University of Toronto
Kevin Kain, University of Toronto
Marie-Christine Chaboissier, Nice, France
Martin Holzenberger, Paris, France
Rohit Kulkarni, Boston
P. Kay Lund, Chapel Hill
Jeff Miner, St. Louis
Chris Rhodes, Chicago
Sylvie Robine, Paris, France
Daniel Storm, Seattle