Andrew McMahon

PIBBS MENTOR

WM Keck Provost Professor
Stem Cell Biology and Regenerative Medicine

Research Topics

* Organ assembly, maintenance, and repair * Stem cells and regenerative medicine

Research Overview

Our interests lie in understanding the developmental processes that build, maintain and repair our organ systems and to utilize the insights gained towards the treatment of disease. Our research focuses on three distinct structures: the kidney, central nervous system and boney skeleton.

The functional unit of the kidney is a long epithelial tube, the nephron. In man, around half a million nephrons make up a kidney. All are formed during fetal life through the controlled expansion and differentiation of a stem/progenitor population. Thereafter, repair of the existing nephrons is the only normal response to chronic and acute injury. We have identified the stem/progenitor cells and we are investigating the signaling factors and transcriptional circuitry that govern nephrogenesis. In addition, we are exploring in vitro approaches to nephron assembly. In the adult, we are using novel genetic systems to investigate damage responses and repair mechanisms. Our goal in this program is to develop therapeutic strategies to diagnose and treat kidney disease.

In the central nervous system, the morphogen Sonic hedgehog (Shh) induces critical neural and glial progenitors in the ventral brain and spinal cord. Shh acts at the top of hierarchy of regulatory factors whose actions lay the foundations of establishment of neural circuitry. We are investigating the mechanism that convert specific levels of Shh signal into distinct transcriptional programs and how cell specific neural programs determine specific neuronal fates through genetic approaches in the mouse, and in vitro stem cell models. Given the importance of Shh dependent cell types in a number of neurological pathologies, including Parkinson’s and Lou Gehrig’s diseases, these studies will enhance efforts to create disease models and to develop cell-based treatments.

The two major biosynthetic lineages for the hard skeleton are bone secreting osteoblasts and cartilage producing chondrocytes. These originate from several distinct tissue sources during development; each source produces a common osteochondroprogenitor that gives rise to chondrocytes and osteoblasts. Understanding how these cell types are specified will enable educated approaches to the restoration of defective tissue on skeletal injury or as a result of degenerative disease.