The gradual loss of insulin-producing beta cells of the endocrine pancreas is common to all forms of diabetes. Elucidating transcriptional complexes that increase our understanding of underlying mechanisms governing pancreatic beta-cell development and function is critical for the development of novel therapeutics that will improve beta-cell function. Loss- and gain-of-function mouse studies have demonstrated critical roles of transcription factors in regulating the establishment and function of beta cells. Preliminary data from our lab and others suggest Lhx1, a LIM-homeodomain transcription factor, is expressed and functions in the developing and adult pancreas. Over the next three years, I propose to investigate in detail the role of Lhx1 in regulating beta-cell development and function using beta cell lines as well as a newly developed conditional knockout model. I hypothesize that Lhx1 is a regulator of endocrine cell development and function.
In Aim 1, I will characterize Lhx1 expression at specific developmental and postnatal stages.
In Aim 2, I will determine Lhx1 gene regulatory mechanisms in beta cells.
In Aim 3, I will characterize the effects of Lhx1 ablation in the developing and adult pancreas using pancreas-specific cre/lox knockout approaches.

Public Health Relevance

Hyperglycemia results from beta cell loss, which if left untreated, leads to frank diabetes and serious secondary health complications. Diabetes Mellitus is a metabolic disorder characterized by either the gradual or absolute loss of insulin-producing pancreatic beta cells. Investigation of transcription factors and co- regulators that govern genes critical to beta cell development and function could lead to beta cell replacement therapies and identify novel drugs that will improve beta cell function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31DK111181-01A1
Application #
9261209
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Rivers, Robert C
Project Start
2017-07-01
Project End
2021-06-30
Budget Start
2017-07-01
Budget End
2018-06-30
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294