Basic Science Research

Andrew Leiter, MD, PhD

Dr. Leiter is an internationally recognized expert on the differentiation of endocrine cells in the pancreas and gastrointestinal tract.  He is also researching ways to develop better animal models of gastrointestinal and pancreatic neuroendocrine tumors for understanding how they arise.

His research relies heavily on transgenic mice as a model to examine developmental biology in the GI tract.  The major areas currently under investigation in the Leiter Laboratory include: 1. Identification of precursor cells that give rise to endocrine precursor cells in the GI tract.  2.  Elucidation of the role of the Wnt, Rb and Notch signaling pathways in regulating cell fate specification in the GI tract.  3. Characterization of the cells from which human carcinoid tumors originate.  4. Analysis of the mechanism that the basic helix loop helix transcription factor, NeuroDi activates gut hormone expression in cells as they terminally differentiate.

Recent work includes:

Ratineau C, Ronco A, Leiter AB. (2000) “Role of the amino-terminal domain of simian virus 40 early region in inducing tumors in secretin-expressing cells in transgenic mice.” Gastroenterology 119, 1305-1311.

Ratineau C, Petry MW, Mutoh H,  Leiter AB. (2002) “Cyclin D1 represses the basic helix-loop-helix transcription factor, BETA2/NeuroD.” J Biol Chem 277, 8847-8853.

Schonhoff SE, Giel-Moloney M, Leiter AB. (2004) “Neurogenin 3-expressing progenitor cells in the gastrointestinal tract differentiate into both endocrine and non-endocrine cell types.” Dev Biol 270, 443-454.

Schonhoff SE,  Baggio L, Ratineau C, Ray SK, Lindner J, Magnuson MA, Drucker DJ, Leiter AB. (2005) “Energy homeostasis and gastrointestinal endocrine differentiation do not require the anorectic hormone, peptide YY.”  Mol Cell Biol. 25, 4189-4199.

Itkin-Ansari P, Marcora E, Geron I, Tyrberg B, Demeterco C, Hao E, Padilla C,  Ratineau C, Leiter A, Lee JE, Levine F.  “NeuroD1 in the endocrine pancreas: localization and activity as an activator and repressor.” (2005) Dev. Dynamics. 233, 946-953.

Wang Y, Giel-Moloney M, Rindi G, Leiter AB. (2007) “Early enteroendocrine progenitor cells develop tumors in response to Wnt  signals but do not require the Wnt pathway for differentiation.” Proc Natl Acad Sci U S A. 104, 11328-11333.

Ray SK, Leiter AB. (2007) “The Basic Helix-Loop-Helix Transcription Factor NeuroD1 Facilitates Interaction of Sp1 with the Secretin Gene Enhancer.” Mol Cell Biol. 27, 7839-7847.

Wang Y, Ray SK, Hinds PW, Leiter AB. (2007) “The retinoblastoma protein, RB, is required for gastrointestinal endocrine cells to exit the cell cycle, but not for hormone expression.” Dev Biol 311, 478-486.