Andrew McMahon, PhD
Frank B. Baird, Jr. Professor of Science
Department of Molecular and Cellular Biology, Faculty of Arts and SciencesHarvard Stem Cell Institute
Department of Stem Cell and Regenerative Biology
Developmental and Regenerative Biology
Investigating the molecular and cellular mechanisms regulating development, repair and regeneration of neural, bone and kidney tissues.
The long-term goal of the McMahon lab is to understand the mechanisms that underlie assembly, repair and regeneration of critical organ systems. The knowledge base will provide an informed, logic-based platform for translating basic research into practical applications in the area of regenerative medicine.
Current Research Interests
Much of our work has centered about the instructive roles of critical signaling factors discovered in our laboratory, principally members of the Wnt and Hedgehog families. As examples, Sonic hedgehog (Shh) is critical for the specification of a broad array of neural progenitor sub-types, several of intense biomedical interest such as motor and dopaminergic neurons. The Shh pathway also underlies a number of cancers and has emerged as target-of-opportunity pursued by a large number of companies. By identifying regulatory processes at the DNA level, we are unraveling the codes for specification of neural cell types and through small molecule screens, new factors to manipulate pathway activity. In the kidney, Wnt signals induce nephron stem/progenitor cells to commit to nephron formation. We are defining the mechanisms that balance commitment and renewal of stem/progenitor types in development, and the injury and repair responses operating in the adult. Two biosynthetic cell types, chondrocytes and osteoblasts, synthesize cartilage and bone to generate and maintain the mammalian skeleton. Each arises from a common progenitor that activates a distinct regulatory program in response to specific BMP, Hedgehog and Wnt signals. This system provides an excellent model to explore the mechanisms that control cell fate specification in the context of two cell types central to regenerative medicine.
Dr. McMahon uses molecular, cellular, and genetic approaches to study the growth, patterning and differentiation of mammalian progenitor cell populations. The Hedgehog pathway is one of the key regulators of development in many organisms, and is involved in cell-cell signaling. The Wnt signaling pathway is also well known for its role in embryogenesis and development. The McMahon lab uses various tools including genetic strategies. The lab has broad knowledge of development, cell signaling and gene regulatory processes.