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Yueming Li, Ph.D.

Head, Laboratory of Biochemistry and Molecular Pharmacology, Memorial Sloan Kettering Cancer Center

Dr. Yueming Li is a Member and Professor of Chemical Biology at Memorial Sloan Kettering Cancer Center and Professor of Pharmacology and Neuroscience at Weill Graduate School of Medical Sciences of Cornell University.  Dr. Li received his Ph.D. degree from the University of California, Berkeley, and subsequently conducted postdoctoral research at Harvard Medical School.  In 1997, Dr. Li joined Merck Research Laboratories where he worked on elucidating the reaction mechanism of β- and γ-secretase, as well as developing protease inhibitors for the treatment of Alzheimer’s disease.  In 2002, he became a faculty member of Memorial Sloan Kettering Cancer Center.  The main interests of Dr. Li’s laboratory are to elucidate the mechanism of γ-secretase-dependent Notch signaling and amyloid precursor protein (APP) processing under physiological and pathological conditions and to develop target-based therapies.  His work in γ-secretase assays, identification and reconstitution of γ-secretase, the regulation of γ-secretase and inhibitor development and the mechanism of action of γ-secretase modulators has significantly advanced our understanding of the molecular pathogenesis of Alzheimer’s disease and therapeutic development. Dr. Li is a recipient of the Zenith Fellows Award from the Alzheimer’s Association, a recipient of the MetLife Foundation 2013 Awards for Medical Research in Alzheimer’s disease, and was elected as an AAAS Fellow of the American Association for the Advancement of Science.

To learn more, visit the Yueming Li Lab website and their social media page.

Related Research:

The Role of Interferon-Induced Transmembrane Protein 3 (IFITM3) and Gamma-Secretase in Microglia Yueming Li 2023-12-21 The Role of Interferon-Induced Transmembrane Protein 3 (IFITM3) and Gamma-Secretase in Microglia Yueming Li 2022-02-15 Biochemical Mapping of the GSM Binding Site of Novel Pyridazine-Derived Small Molecule Gamma-Secretase Modulators Steven L. Wagner Yueming Li 2018-08-09 Discovery of Alzheimer’s Disease Blood Biomarkers Using Phage Display Technology Yueming Li 2014-01-27

Funded Research

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

Project Description Researchers Funding
The Role of Interferon-Induced Transmembrane Protein 3 (IFITM3) and Gamma-Secretase in Microglia 2023

$230,000
The Role of Interferon-Induced Transmembrane Protein 3 (IFITM3) and Gamma-Secretase in Microglia 2021, 2022

$345,00
Biochemical Mapping of the GSM Binding Site of Novel Pyridazine-Derived Small Molecule Gamma-Secretase Modulators 2017 and 2019

$600,000
Discovery of Alzheimer’s Disease Blood Biomarkers Using Phage Display Technology 2013, 2015

$200,000

Selected Publications

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

Wong, E., Malviya, M., Jain, T., Liao, G. P., Kehs, Z., Chang, J. C., Studer, L., Scheinberg, D. A., & Li, Y. M. HuM195 and its single-chain variable fragment increase Aβ phagocytosis in microglia via elimination of CD33 inhibitory signaling, Molecular Psychiatry, February 21, 2024, Read More

Zhang, X., Hoey, R. J., Lin, G., Koide, A., Leung, B., Ahn, K., Dolios, G., Paduch, M., Ikeuchi, T., Wang, R., Li, Y. M., Koide, S., & Sisodia, S. S. Identification of a tetratricopeptide repeat-like domain in the nicastrin subunit of gamma-secrtase using synthetic antibodies, Proceedings of the National Academy of Sciences of the United States of America, May 14, 2012, Read More

Zhang, X., Sullivan, E., Scimeca, M., Wu, X., Li, Y. M., & Sisodia, S. S. Evidence that the “Lid” domain of nicastrin is not essential for regulating secretase activity, Journal of Biological Chemistry, February 17, 2016, Read More

Nie, P., Vartak, A., & Li, Y. M. γ-Secretase Inhibitors and Modulators: Mechanistic Insights Into the Function and Regulation of γ-Secretase, Seminars in Cell & Developmental Biology, April 2, 2020, Read More

Frost, G. R., Longo, V., Li, T., Jonas, L. A., Judenhofer, M., Cherry, S., Koutcher, J., Lekaye, C., Zanzonico, P., & Li, Y. M. Hybrid PET/MRI Enables High-Spatial Resolution, Quantitative Imaging of Amyloid Plaques in an Alzheimer’s Disease Mouse Model, Scientific Reports, June 25, 2020, Read More

Frost, G. R., Jonas, L. A., & Li, Y. M. Friend, Foe or Both? Immune Activity in Alzheimer’s Disease, Frontiers in Aging Neuroscience, December 10, 2019, Read More

Mekala, S., Nelson, G., & Li, Y. M. Recent developments of small molecule γ-secretase modulators for Alzheimer’s disease, RSC Medicinal Chemistry, August 27, 2020, Read More

Frost, G. R., Wong, E., & Li, Y. M. Versatility of presenilin 1, Proceedings of the National Academy of Sciences of the United States of America, June 23, 2017, Read More

Jonas, L. A., Jain, T., & Li, Y. M. Functional insight into LOAD-associated microglial response genes, Open Biology, January 26, 2022, Read More

Frost, G. R., & Li, Y. M. The role of astrocytes in amyloid production and Alzheimer’s disease, Open Biology, December 13, 2017, Read More

Wong, E., Frost, G. R., & Li, Y. M. γ-Secretase Modulatory Proteins: The Guiding Hand Behind the Running Scissors, Frontiers in Aging Neuroscience, December 2, 2020, Read More

Liu, C., Nikain, C., & Li, Y. M. γ-Secretase fanning the fire of innate immunity, Biochemical Society Transactions, August 31, 2023, Read More

Wagner, S. L., Zhang, C., Cheng, S., Nguyen, P., Zhang, X., Rynearson, K. D., Wang, R., Li, Y., Sisodia, S. S., Mobley, W. C., & Tanzi, R. E. Soluble gamma-secretase modulators slectively inhibit the production of the 42 amino-acid amyloid beta peptide variant and augment the production of multiple carboxy-truncated amyloid beta species, Biochemistry, January 22, 2014, Read More

Zhang, X., Hoey, R., Koide, A., Dolios, G., Paduch, M., Nguyen, P., Wu, X., Li, Y., Wagner, S. L., Wang, R., Koide, S., & Sisodia, S. S. A synthetic antibody fragment targeting nicastrin affects assembly and trafficking of gamma-secretase, Journal of Biological Chemistry, October 28, 2014, Read More

Barros, M., Houlihan, W. J., Paresi, C. J., Brendel, M., Rynearson, K. D., Lee, C. W., Prikhodko, O., Cregger, C., Chang, G., Wagner, S. L., Gilchrist, M. L., & Li, Y. M. Gamma-Secretase Partitioning Into Lipid Bilayers Remodels Membrane Microdomains After Direct Insertion, Langmuir, May 20, 2020, Read More

Ahn, K., Shelton, C. C., Tian, Y., Zhang, X., Gilchrist, M. L., Sisodia, S. S., & Li, Y. M. Activation and intrinsic gamma-secretase activity of presenilin 1, Proceedings of the National Academy of Sciences of the United States of America, November 29, 2010, Read More

Hur, J. Y., Frost, G. R., Wu, X., Crump, C., Pan, S. J., Wong, E., … Vassar, R., … Greengard, P., ... Li, Y. M. The innate immunity protein IFITM3 modulates γ-secretase in Alzheimer’s disease, Nature, September 2, 2020, Read More

Kleffman, K., Levinson, G., Rose, I., Blumenberg, L. M., … Li, Y. M., … Liddelow, S.A., … Hernando, E. Melanoma-Secreted Amyloid Beta Suppresses Neuroinflammation and Promotes Brain Metastasis, Cancer Discovery, May 2, 2022, Read More

Luo, J. E., & Li, Y. M. Turning the tide on Alzheimer’s disease: modulation of γ-secretase., Cell & Bioscience, January 4, 2022, Read More

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