In my laboratory, we pursue two interlocking areas of investigation: the basic biology of stem cell programming and reprogramming, as well as the application of the resulting technologies to studies of the neuromuscular system and the diseases that affect it.
A fundamental understanding of how a cell's identity is determined during differentiation and how it can in turn be manipulated experimentally is a central goal of developmental biology, one with substantial ramifications for biomedicine. We study both the differentiation of embryonic stem cells into the neural lineage and the reprogramming of commonly available differentiated cell types, such as fibroblasts, into either pluripotent stem cells or cells of therapeutic interest, such as spinal motor neurons. To study differentiation and dedifferentiation, we employ a variety of approaches, including stem cell differentiation, nuclear transfer, and defined reprogramming strategies using known transcriptional regulators and novel small-molecule compounds.
A number of devastating diseases, including amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), specifically affect the neuromuscular system. Little is known concerning the molecular pathology underlying these conditions, partly because it has been impossible to access significant quantities of the disease-affected cell, the spinal motor neuron. With recent advances in stem cell and reprogramming biology, we can now produce billions of spinal motor neurons with control and diseased genotypes. We use this new resource to design in vitro disease models for both mechanistic studies and for the discovery of novel small-molecule therapeutics.
This work is supported in part by grants from the National Institutes of Health, Project A.L.S., and the New York Stem Cell Foundation.
As of May 30, 2012