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Subhash Sinha, Ph.D.

Associate Professor of Research in Neuroscience, Weill Cornell Medicine

Dr. Subhash Sinha serves as an Associate Professor of Research in Neuroscience at Weill Cornell Medicine, where he leads pioneering efforts in the discovery and development of small-molecule drugs to combat neurodegenerative diseases, notably Alzheimer’s and Parkinson’s. His research encompasses the identification of promising chemical compounds and the evaluation of their potential therapeutic effects, which can further elucidate underlying disease mechanisms. Dr. Sinha has identified compounds that modulate the metabolism of amyloid precursor protein (APP) to favor non-amyloidogenic pathways, thereby reducing amyloid-β production. These compounds also induce autophagy, promoting the clearance of toxic protein aggregates. Notably, his research has highlighted the potential of certain Bcr-Abl kinase inhibitors, like nilotinib, which are currently undergoing clinical trials for Parkinson’s disease.

Dr. Sinha actively collaborates with esteemed colleagues, including Drs. Li Gan, Anna Orr, and Adam Orr at Weill Cornell Medicine, as well as Drs. Rudolph E. Tanzi and Ana Griciuc at Massachusetts General Hospital and Harvard University. In these partnerships, he works to discover novel compounds that modulate microglial functions, the brain’s resident immune cells, by targeting key molecules involved in neuroinflammation, such as cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING), Toll-like receptor 7 (TLR7), mitochondrial reactive oxygen species (mtROS) production by Complex III, and CD33. They have already identified some potent inhibitors of these targets using high throughput screening and hit-to-lead discovery. Through these endeavors, Dr. Sinha strives to translate his findings into effective clinical treatments, ultimately improving the quality of life for individuals affected by neurodegenerative diseases.

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.

Alarcón-Espósito, J., Nagiri, R. K., Gan, L., & Sinha, S. C. Identification and development of cGAS inhibitors and their uses to treat Alzheimer’s disease, NeuroTherapeutics, January 31, 2025, Read More

Lopez-Lee, C., Kodama, L., Fan, L., Zhu, D., Zhu, J., Wong, M. Y., Ye, P., Norman, K., Foxe, N. R., Ijaz, L., Yu, F., Chen, H., Carling, G. K., Torres, E. R., Kim, R. D., Dubal, D. B., Liddelow, S. A., Sinha, S. C., Luo, W., & Gan, L. Tlr7 drives sex differences in age- and Alzheimer’s disease-related demyelination, Science, November 29, 2024, Read More

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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