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Dr. Anil Shanker, PhD

Meharry Medical College

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Meharry Medical College

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The Shanker laboratory studies information processing and molecular circuitry underlying lymphocyte crosstalk. Using the TCR-transgenic mice specific to cancer-germline self-antigen P1A, akin to human MAGE antigens (J Immunol172:5069), our pioneering studies discovered a paradigm of CD8 T cell help for innate NK effector function in solid tumor microenvironments. This CD8 T–NK crosstalk enhances immunosurveillance against tumor development and prevents tumor escape (J Immunol 179:6377).  Our ongoing work has identified mitochondrial Ca2+ transport-mediated intermembranous interaction critical during CD8 T–NK cooperativity to elicit NK cell effector/regulatory and T cell memory functions. We also found that CD8 T cells preferentially use death ligands to clear metastasis of tumor cells expressing low-avidity antigens (Cancer Res 69:6615). These findings provide for novel immunotherapy approaches that we are exploring to prevent tumor development, escape and metastasis. In breast, kidney and inducible EGFR-mutant lung cancer mouse models, and patient samples in a multi-institutional collaboration, we are testing adoptive transfer protocols of CD8 T and NK cells in combination with engineered Notch ligand constructs (Cancer Res 71:6122, 75:4728; JITC 7:95), bortezomib, a proteasome inhibitor (J Immunol 180:163; JNCI 100:649; Cancer Res 75:5260), and neurotransmitter agonists. We are defining Notch-associated T cell immunoscore signature from animal models and NSCLC patients. Our efforts are also invested in building computational modelsthat guide cell fate and lymphocyte functional crosstalk (Open Biol 6:160192; Front Immunol 10:1906). The laboratory provides a vibrant research environment for mentoring undergrad, doctoral, postdoctoral and medical trainees from diverse backgrounds.

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