Subhash Sinha, Ph.D.

Assistant Professor of Research Neuroscience, Weill Cornell Medicine

Dr. Sinha’s research focuses on the development of natural and non-natural products as tools and potential treatments for neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Accumulation of misfolded peptides and proteins, such as amyloid-β peptide and hyperphosphorylated tau protein in Alzheimer’s and α-synuclein in Parkinson’s, are likely causative to these diseases, and compounds reducing the levels of misfolded peptides and proteins are highly desirable.

In recent years, Dr. Sinha has focused on compounds that reduce amyloid-β production through shifting the amyloid precursor protein (APP) metabolism from the amyloidogenic to the non-amyloidogenic pathway. Some of these compounds also induce autophagy, such as the related Brc-Abl kinase inhibitor nilotinib, but do so independent of kinase inhibition. Nilotinib is currently undergoing clinical trials for treatment of Parkinson’s disease. The other class of compounds are CK1γ2 autophosphorylation inhibitors that mediate autophagy through increasing PS1 Ser-367 phosphorylation. Sinha and his team are collaborating with Paul Greengard’s lab, which has recently identified PS1 Ser-367 phosphorylation as playing a key role in amyloid-β production through mediating autophagic degradation of its precursor, the APP β-CTF.

Dr. Sinha and his colleagues are also developing a DNA-encoded library that can be used to screen various targets of interest, including phosphorylation-related enzymes and receptors, relevant for central nervous system diseases. There are vast opportunities in these areas for the understanding of enzyme functions and drug development. Similarly, they are exploring the possibility of selective and effective treatment of central nervous system disorders using G protein-coupled receptors.

Funded Research

These projects were made possible from Cure Alzheimer's Fund support.

Selected Publications

These published papers resulted from Cure Alzheimer’s Fund support.

Bustos, V. H., Sunkari, Y. K., Sinha, A., Pulina, M., Bispo, A., Hopkins, M., Lam, A., Kriegsman, S. F., Mui, E., Chang, E., Jedlicki, A., Rosenthal, H., Flajolet, M., & Sinha, S. C. Rational Development of a Small-Molecule Activator of CK1γ2 That Decreases C99 and Beta-Amyloid Levels, ASC Chemical Biology, December 11, 2023, Read More

Huang, Y., Liu, B., Sinha, S. C., Amin, S., & Gan, L. Mechanism and therapeutic potential of targeting cGAS-STING signaling in neurological disorders, Molecular Neurodegeneration, November 8, 2023, Read More

Udeochu, J. C., Amin, S., … Tsai, L. H., Subhash, S. C., & Gan, L. Tau activation of microglial cGAS–IFN reduces MEF2C-mediated cognitive resilience, Nature Neuroscience, April 24, 2023, Read More