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    Zhengyu Ma, PhD

    Research Scientist

    Nemours Children's Hospital, Delaware 1600 Rockland Road Wilmington, DE 19803

    Biography

    Education M.D. – Qingdao Medical College, Shandong, China M.S. – Chinese Academy of Medical Sciences, Beijing, China Ph.D. – University of Pennsylvania, Philadelphia, Pennsylvania Postdoctoral – The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania Research Interest: Dr. Zhengyu (Mark) Ma is a Research Scientist at Nemours Children's Health, Delaware, and the Head of the T Cell Immunology Lab. The Lab focuses on the development of immunotherapies for cancer and immune-related diseases. For cancer, Dr. Ma works on both cancer-targeting T cells including chimeric antigen receptor (CAR) T cells and immune checkpoint blockade antibodies. These two areas witnessed major breakthroughs in recent years with multiple therapies recently approved by FDA. CAR T cells are generated through genetic modification of patents' T cells to express CARs that recognize antigens on cancer cells. CAR T cells have been highly effective in treating B cell leukemia and lymphoma, but the success has not been translated to treating solid tumors. Dr. Ma is developing novel T cell-based immunotherapies for solid tumors by taking advantage of T cells' ability to attack solid organs through alloreactivity, which is the mechanism underlying organ transplant rejection. Dr. Ma is also active in identifying novel targets for immune checkpoint blockade antibodies. T cells express immune checkpoint receptors that deliver inhibitory signals upon engaging immune checkpoint ligands expressed on normal tissues. Immune checkpoints are critical for tuning down immune responses after elimination of pathogens to prevent out-of-control inflammation or autoimmune diseases. Cancer cells often highjack this mechanism to evade immune attack. Immune checkpoint blockage antibodies liberate T cells from the inhibition and have demonstrated strong efficacy but only for certain solid tumors in some patients. Most antibodies target the receptor PD-1 or its ligand PD-L1. Dr. Ma's lab aims to identify additional targets to enhance the efficacy of this approach. Finally, Dr. Ma is working on developing CAR T cells that target B cells that produce IgE, the key mediator of allergic responses, to treat severe allergic diseases such as severe allergic asthma and food allergies.

    Medical/Dental School

    • MBBS - Qingdao University Medical College, Laboratory Medicine
    • MS - Chinese Academy of Medical Sciences & Peking Union Medical College, Biochemistry
    • PhD - University of Pennsylvania, Immunology, 2016

    • Directing T cell alloreactivity against solid tumors through tumor antigen dependent TCR expression; The Journal of Immunology; (2022).

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    • Targeting IgE-producing blood cancers using EMPD-specific chimeric antigen receptor T cells; Regular and Young Investigator Award Abstracts; (2022).

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    • The Nemours Foundation, assignee. Adoptive T-cell therapy using EMPD-specific chimeric antigen receptors for treating IgE-mediated allergic diseases; Unknown Source; (2022).

    • Tumor-activated alloreactive and xenoreactive T cells and their use in immunotherapy against cancer. USA patent application ; Unknown Source; (2020).

    • The Nemours Foundation, assignee. Adoptive T-cell therapy using FcεRI-based chimeric antigen receptors for treating IgE-mediated allergic diseases. ; Unknown Source; (2019).

    • Chimeric Antigen Receptors Based on Low Affinity Mutants of FcεRI Re-direct T Cell Specificity to Cells Expressing Membrane IgE; Frontiers in Immunology; (2018).

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    • REDD1 Is Essential for Optimal T Cell Proliferation and Survival; PLOS ONE; (2015).

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    • Chimeric antigen receptors based on low affinity mutants of FcεRI re-direct T cell specificity to cells expressing membrane IgE (HYP5P.321); The Journal of Immunology; (2015).

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    • The impact of Nucleofection® on the activation state of primary human CD4 T cells; Journal of Immunological Methods; (2014).

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    • TCR Triggering by pMHC Ligands Tethered on Surfaces via Poly(Ethylene Glycol) Depends on Polymer Length; PLoS ONE; (2014).

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    • Strength of PD-1 signaling differentially affects T-cell effector functions; Proceedings of the National Academy of Sciences; (2013).

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    • Mechanical Force in T Cell Receptor Signal Initiation; Frontiers in Immunology; (2012).

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    • Improved method of preparation of supported planar lipid bilayers as artificial membranes for antigen presentation; Microscopy Research and Technique; (2011).

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    • T cell receptor triggering by force; Trends in Immunology; (2010).

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    • Surface-Anchored Monomeric Agonist pMHCs Alone Trigger TCR with High Sensitivity; PLoS Biology; (2008).

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    • The receptor deformation model of TCR triggering; The FASEB Journal; (2008).

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    • Complement Receptor 3 Ligation of Dendritic Cells Suppresses Their Stimulatory Capacity; The Journal of Immunology; (2007).

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    • Effective gene suppression using small interfering RNA in hard-to-transfect human T cells; Journal of Immunological Methods; (2006).

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    • Ligation of CD28 by Its Natural Ligand CD86 in the Absence of TCR Stimulation Induces Lipid Raft Polarization in Human CD4 T Cells; The Journal of Immunology; (2005).

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    • Embryonic and hematopoietic stem cells express a novel SH2–containing inositol 5′-phosphatase isoform that partners with the Grb2 adapter protein; Blood; (2001).

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