Our laboratory is broadly interested in the mechanisms underlying changes in the nervous system as a result of aging or disease, as well as the interactions between the nervous system and the rest of the body that mediate health versus disease. Studies involve a variety of in vivo, in vitro, and in silico approaches to generate insights into the complex molecular pathways underlying different disease states with a goal of identifying novel therapeutic avenues. Current efforts in the lab include studies of the aging brain, CNS disorders (including neuromuscular and neurodegenerative) and skeletal muscle disorders.
Lee Rubin, Ph.D.
- Professor of Stem Cell and Regenerative Biology
- Co-director, Harvard Stem Cell Institute Nervous System Disease Program
- Executive Committee Member
Harvard Stem Cell Institute
Lee Rubin investigates the key molecular mediators of different neurodegenerative diseases, with the ultimate goal of finding effective preclinical therapeutic candidates. His research group discovered that a circulating protein, GDF11, has the ability to reverse some of the changes in the CNS associated with aging. They are actively exploring the therapeutic implications of these observations.
The Rubin group takes advantage of their ability to produce large numbers of patient-derived induced pluripotent stem (iPS) cell lines and of effective means of deriving large numbers of differentiated neurons from them. They have set up an array of techniques that allow them to identify early cellular and physiological changes in neurons as they become diseased. For example, they have identified new targets for the treatment of the motor neuron disorders Spinal Muscular Atrophy (SMA) and Amyotrophic Lateral Sclerosis (ALS). They are also studying Autism Spectrum Disorders, Parkinson’s disease and Alzheimer’s disease.
Dr. Rubin received his Ph.D. in Neuroscience from The Rockefeller University and completed postdoctoral fellowships in Pharmacology from Harvard Medical School and in Neurobiology from Stanford University School of Medicine. He has a broad experience in both academia and industry, particularly in the realms of cell-based assays and drug discovery. Prior to coming to Harvard, Rubin was Chief Scientific Officer of Curis, Inc., a Cambridge-based biotechnology company, where his group identified the first small molecule regulators of the hedgehog signaling pathway. One of their antagonists was developed by Genentech and is now (as Erivedge) approved as the first oral treatment for metastatic basal cell carcinoma.
Skeletal MuscleNeuromuscular disorders, such as Spinal Muscular Atrophy (SMA), often comprise a skeletal muscle defect in addition to the problems in the nervous system. SMA patients present with widespread muscle atrophy and weakness. Skeletal muscle tissue is known to regenerate rather well, a capability that is attributed to the activity of satellite cells, the resident skeletal muscle stem cell. We are carrying out studies to evaluate whether or not defects in satellite cells may contribute to neuromuscular diseases. Our research combines the use of SMA patient-derived iPSCs, genetic mouse models, and phenotypic drug screening methods.
Small Molecule Screening AssaysWe have established an extensive range of complex, image-based assays to probe the properties of stem cells and cells derived from them. We use automated, high-content screening imagers, associated robotic equipment, and selected small molecule libraries and combine this high throughput approach with detailed molecular studies to further our understanding of the mechanisms of disease and determine which compounds are most likely to be of therapeutic value.