Research in the Drucker lab is focused on understanding the biology of the glucagon-like peptides. Specific projects include physiological analyses of GLP-1 and GLP-2 action, understanding the biology of glucagon action, and elucidation of the functional control of both GLP-1 and GLP-2 action through studies of their respective receptors.
Students and research fellows utilize a combination of techniques that involve cell culture, gene microarray and proteomic experiments, studies of signal transduction, cell proliferation and apoptosis, with a major emphasis on generation and phenotypic analysis of transgenic or knockout mice. The lab employees rodent models to delineate novel concepts of glucagon-like peptide action with a focus on potential therapeutic relevance to diabetes and intestinal disease.
Glucagon-like peptide-1
The lab maintains an active research interest in studying multiple aspects of GLP-1 action, including the GLP-1-regulated control of glucose homeostasis, and the role of GLP-1 signaling in the central nervous system. These studies employ cell lines, normal rodents, transgenic mice that over-express GLP-1 analogues, and mice with disrupted GLP-1 receptor signaling. The lab is also interested in studying the biology of exendin-4 action using studies of GLP-1 receptor -/- mice and cell and murine models. The lab uses a combination of approaches to delineate the physiological actions of GLP-1 including analyses of Glp1r-/- mice to understand the importance of GLP-1 for glucoregulation, islet growth, and apoptosis. The lab is also interested in the role of GLP-1 in the cardiovascular system and in the CNS. We are also carrying out studies to rescue GLP-1 receptor function in specific murine tissues via a transgenic approach in vivo. The importance of dipeptidyl peptidase-4 (DPP-4) for the control of incretin action is also an important focus of research investigation.
Glucagon-like peptide-2
The lab is using mouse genetics and both gain and loss of function experiments to understand the role of GLP-2 in vivo.
Current projects include studies of the regulation of GLP-2 receptor expression and GLP-2 receptor signaling, and studies of both gain and loss of GLP-2 receptor signaling in vitro and in vivo. The lab employs rodent models of intestinal disease to identify potential therapeutic actions of GLP-2 in vivo. A major focus of the lab is to understand GLP-2 action via studies of GLP-2 receptor signaling in vitro, and by analysis of the downstream targets of GLP-2 in vivo.
Glucagon
The lab continues to focus on studies directed at understanding the physiology of glucagon action and wherever possible uses mouse models to complement data obtained from cell-based studies in vitro. More recent studies are focused on analysis of tissue-specific control of glucagon receptor action using genetically engineered mice, as exemplified by Gcgr-/- mice..
Dipeptidyl peptidase-4 (DPP-4)
Given the importance of this key peptidase in the control of both GLP-1 and GLP-2 degradation, and its role as a key drug target for diabetes therapeutics, the laboratory is interested in the biology of DPP-4, and its importance in the control of multiple metabolic functions. Similarly, the laboratory also studies the biology of the related incretin GIP, and the PGDP oxyntomodulin.
For an overview of recent work, see Drucker Lab Publications