Nathan Singh, M.D., M.S.

Assistant Professor
Internal Medicine
Oncology

Immunology Program
Cancer Biology Program

  • 643 Southwest Tower

  • nathan.singh@wustl.edu

  • https://sites.wustl.edu/nathansinghlab

  • @nathansinghlab1

  • CAR T cell therapy, immunotherapy for cancer, T cell signaling, T cell dysfunction, lineage decisions

  • Understanding how synthetic antigen receptors direct T cell function and dysfunction in the treatment of blood cancers

Research Abstract:

Chimeric antigen receptors, or CARs, are synthetic proteins that can re-direct T cells to robustly target and kill cancer cells. Early clinical trials revealed impressive results in the treatment of B cell leukemia and lymphoma, representing a breakthrough in the treatment of these diseases with historically poor outcomes. Despite promising early results, long-term follow-up has revealed that many patients will not respond to these therapies, and that many who do respond will ultimately relapse.

Using a variety of classical and novel techniques, we aim to understand how CARs in some cases drive effective T cell function against cancer, and in others lead to the development of T cell dysfunction that prevents successful anti-cancer activity. From basic receptor biochemistry and signaling to epigenetic imprinting, we aim to develop a blueprint of how these synthetic receptors direct T cell molecular programming. Using knowledge of these essential pathways, we hope to use novel genome engineering techniques to overcome detrimental cellular circuitry to develop enhanced, "intelligent" cellular therapies for cancer that are more effective, more durable and yield more long-term remissions for patients with blood cancers.

Selected Publications:

Singh N., Lee, Y.G., Shestova, O., Ravikumar, P., Hayer, K., Hong, S.J., Lu, X., Pajarillo, R., Agarwal, S., Kuramitsu, S., Orlando, E., Mueller, K., Good, C.R., Berger, S.L., Shalem, O., Weitzman, M.D., Frey, N.V., Maude, S.L., Grupp, S.A., June, C.H., Gill, S. and Ruella, M. Impaired death receptor signaling in leukemia causes antigen-independent resistance by inducing CAR T cell dysfunction”. Cancer Discovery, 2020, In press.

Singh, N., Orlando, E., Xu, J., Xu, J., Binder Z., Collins, M.A., O’Rourke, D.M. and Melenhorst, J.J. Mechanisms of resistance to CAR T cell therapies. Seminars in Cancer Biology, 2019, In Press.

Singh, N., Hofmann, T.J., Gershenson, Z., Levine, B.L., Grupp, S.A., Teachey, D.T. and Barrett, D.M. Monocyte lineage-derived IL-6 does not not affect chimeric antigen receptor T-cell function. Cytotherapy, 2017 Jul;19(7):867-880.

Singh, N., Perazzeli, J., Grupp, S.A. and Barrett, D.M. Early memory phenotypes drive T cell proliferation in patients with pediatric malignancies. Science Translational Medicine, 2016 Jan6;8(320):320ra3.

Last Updated: 1/14/2020 1:10:28 PM

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