Cure Alzheimer's Fund Cure Alzheimer's Fund

Subhash Sinha, Ph.D.

Associate Professor of Research in 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.

Related Research:

Sex-biased Toll-Like Receptor 7 (TLR7) Signaling in Demyelination and its Inhibition by Small Molecules Li Gan Subhash Sinha 2024-11-23 Identification and Development of CD33 Inhibitors and Pre-RNA Splicing Modulators Subhash Sinha 2023-10-25 Development of Human cGAS Inhibitors to treat Alzheimer’s Disease Li Gan Subhash Sinha 2022-02-11 Identification of CD33 Antagonists Subhash Sinha 2021-01-05 The Development of DNA-Encoded Libraries to Discover Therapeutically Valuable Low Molecular Weight Compounds for Alzheimer’s Disease Marc Flajolet Subhash Sinha 2019-01-10

Funded Research

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

Project Description Researchers Funding
Sex-biased Toll-Like Receptor 7 (TLR7) Signaling in Demyelination and its Inhibition by Small Molecules 2024

$402,500

Identification and Development of CD33 Inhibitors and Pre-RNA Splicing Modulators 2023, 2024

$402,500
Development of Human cGAS Inhibitors to treat Alzheimer’s Disease 2021-2023

$750,000
Identification of CD33 Antagonists 2020, 2022

$345,000
The Development of DNA-Encoded Libraries to Discover Therapeutically Valuable Low Molecular Weight Compounds for Alzheimer’s Disease 2018

$172,500

Selected Publications

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

Carling, G. K., Fan, L., Foxe, N. R., Norman, K., Wong, M. Y., Zhu, D., Corona, C., Razzoli, A., Yu, F., Yarahmady, A., Ye, P., Chen, H., Huang, Y., Amin, S., Sereda, R., Lopez-Lee, C., Zacharioudakis, E., Chen, X., Xu, J., Cheng, F., … Gan, L. Alzheimer’s disease-linked risk alleles elevate microglial cGAS-associated senescence and neurodegeneration in a tauopathy model, Neuron, September 24, 2024, Read More

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

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