Andrew McMahon is a USC Provost Professor and holder of the inaugural W. M. Keck Professorship of Stem Cell Biology and Regenerative Medicine. In addition, he chairs the newly created Department of Stem Cell Biology and Regenerative Medicine at the USC Keck School of Medicine and holds an appointment in the Department of Biological Sciences in the USC Dornsife College of Letters, Arts, and Sciences. McMahon and his team study the mechanisms underlying the assembly, repair, and regeneration of critical organ systems in the developing mammalian embryo.
Focusing on two major mammalian organ systems, the central nervous system and the kidney, McMahon and his team study precursor cells that guide stem cell development in order to identify factors that control the generation of particular structures. McMahon’s research provides new information about normal and abnormal development, as well as repair systems operating in the adult body, in order to enable approaches to repair and replacement of human tissues and organs.
Working with large data sets in the range of 10 to 30 gigabytes, McMahon’s lab employs HPCC resources for bioinformatics analysis of next-generation sequencing data, including experiments to monitor protein-DNA interactions using ChIP-seq, a sequencing method combining chromatin immunoprecipitation (ChIP) with massively parallel sequencing. Determining how proteins and DNA interact to regulate gene expression is critical to understanding numerous disease states and biological processes. McMahon also uses quantitation of gene expression levels via RNA-seq—a high-throughput, next-generation DNA sequencing technology—as well as through the alignment of short sequence reads, detection of enriched regions, de novo motif discovery, motif mapping, and measuring transcripts. The group also collaborates with computational scientists in the USC Dornsife College to search for new biological activities encoded within the RNA of repairing cells.
McMahon’s findings in the area of mammalian signaling factors led to the founding of the start-up company Ontogeny (later Curis) in 1994, and ultimately, through the licensing of small molecules identified in screens at Curis, the development of a novel anti-cancer drug by Genentech, Vismodegib, the first FDA-approved hedgehog pathway inhibitor. Vismodegib was developed to fight basal-cell carcinoma, a type of skin cancer, and is also undergoing clinical trials for the treatment of metastatic colorectal cancer, small-cell lung cancer, advanced stomach cancer, pancreatic cancer, medulloblastoma, and chondrosarcoma.
McMahon serves as director of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, which investigates the biological mechanisms that control stem cell behavior in order to provide a platform for translating basic research into practical applications, such as drug therapies. McMahon also leads a new cross-USC initiative, USC Stem Cell, which aims to maximize the potential of research and translation in this area across the university, with a shared focus on regenerative medicine. In this capacity, McMahon also collaborates with teams from other regional institutes to develop novel platforms in imaging, bioengineering, and nanotechnology for application to stem cell research.
McMahon is an elected fellow of the American Association for the Advancement of Science, the American Academy of Arts; Sciences, and The Royal Society (London), as well as an elected associate member of the European Molecular Biology Organization. Major funders for his work include the California Institute for Regenerative Medicine, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Institute of Neurological Disorders and Stroke.
ABOVE: Kidney progenitor/stem cells (green) cluster around the tips of the branching ureteric network (red) in the developing kidney.