Harvard Catalyst Profiles

Trained as both a physician and a basic research scientist, Yuyu Song has a primary interest in research projects related to adult-onset neurodegenerative diseases, with a focus on Amyotrophic Lateral Sclerosis (ALS) and Alzheimer’s Disease (AD). This interest was first stimulated by her clinical experiences and eventually led to graduate work that explored topics related to both normal neural development and neurodegeneration including: 1) specializations of the neuronal cytoskeleton that are essential for normal neuronal structure and function; and 2) molecular mechanisms underlying adult-onset neurodegenerative diseases. This includes AD, ALS, Huntington’s Disease (HD), Parkinson’s Disease (PD), and HIV neuropathy. Inspired by the possibility of conducting translational neuroscience research, Dr. Song obtained postdoctoral training at Boston Children’s Hospital/Harvard Medical School, where she studied childhood neurological diseases caused by tubulin mutations. This work explored the puzzle of selective vulnerability of neurons in various neuromotor disorders and led her to Dr. Arthur Horwich’s laboratory at HHMI/Yale School of Medicine. There she examined the molecular mechanism of ALS via three areas that might provide insights into the puzzle: 1) protein misfolding/quality control and molecular chaperones; 2) axonal transport deficits and altered motor protein behavior; and 3) synaptic dysfunction and aberrant Ca2+ influx. Her work revealed signaling pathways that connect these three aspects of disease pathology, and that may also involve the innate immune response and neuroinflammation. As the intertwined and multifactorial pathogenesis of these diseases emerged and suggested potential therapeutic approaches, Dr. Song joined the Laboratory of Systems Pharmacology at the Harvard Medical School. Here she aims to develop new drugs and/or repurpose and modify existing ones, that target the signaling pathway components and neuronal cytoskeletal disruptions observed in neurodegenerative diseases.