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overview Dr. Anil Shanker leads the Laboratory of Lymphocyte Function in the Department of Biochemistry and Cancer Biology at Meharry Medical College School of Medicine. He is also a member of the Host-Tumor Interactions Research Program of Vanderbilt-Ingram Comprehensive Cancer Center (VICC) at Vanderbilt University. After completing his Master’s degree in Zoology/Cell Biology at the University of Delhi, Dr. Shanker obtained his PhD in tumor immunobiology from Banaras Hindu University, India in 1999. He performed his postdoctoral studies in tumor immunology at the CNRS/INSERM Center of Immunology (CIML), Marseille, France from 2000 to 2003, and at the National Cancer Institute, Frederick, Maryland from 2003 to 2008. He worked as Scientist I in the Cancer and Inflammation Program at the NCI from 2008 to 2010, before joining as faculty at Meharry Medical College. 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 Immunol 172:5069), our pioneering studies discovered a paradigm of CD8 T cell help for innate NK effector function in solid tumor microenvironments. Such a potentiated 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. Our efforts are also invested in building computational models that guide cell fate and lymphocyte functional crosstalk (Open Biol 6:160192; Front Immunol 10:1906). The laboratory provides a vibrant research environment for mentoring its undergrad, doctoral, postdoctoral and medical trainees from diverse backgrounds.
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