Publication Date

2019-12-10

Availability

Embargoed

Embargo Period

2021-12-09

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Molecular Cell and Developmental Biology (Medicine)

Date of Defense

2019-10-30

First Committee Member

Juan Dominguez-Bendala

Second Committee Member

Nevis L. Fregien

Third Committee Member

Claudia de Oliveira Rodrigues

Fourth Committee Member

Ernesto Bernal Mizrachi

Abstract

Glucose homeostasis is maintained and tightly regulated via production of key hormones that control the uptake and metabolism of glucose. β-cells, which secrete insulin, are the subject of autoimmune destruction in type 1 diabetes. From a developmental standpoint, Bone Morphogenetic Protein receptors (BMPRs) have a key role in multiple cell processes, including proliferation and differentiation. Targeting these receptors to identify and induce the proliferation of progenitor cells could have therapeutic applications. Previous studies have shown the conversion of the exocrine compartment of the pancreas to form insulin-producing cells. In this context, we have identified a cell residing in the pancreatic ducts that is positive for Activin Receptor Like Kinase 3 (ALK3, a BMPR) and Pancreatic Duodenal Homeobox 1 protein (PDX1) but negative for carbonic anhydrase II (CAII), which is a mature ductal marker. We hypothesize that these ALK3+/PDX1+/CAII- cells that reside in pancreatic ducts are responsive to Bone Morphogenetic Protein 7 (BMP7) stimulation. My goal is to allow for the stimulation of these cells in vivo, inducing their proliferation and later differentiation into endocrine (particularly insulin+) cells. This research will contribute towards a better understanding of regenerative processes in the pancreas.

Keywords

Pancreas; Pancreatic Progenitors; Pancreatic Stem cells; BMP-7; ALK3; BMPR1A

Available for download on Thursday, December 09, 2021

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