Anil Shanker Phd Email Address

Professor and Coordinator, Cancer Immunotherapy

Meharry Medical College, founded in 1876, is the nation's largest, private, independent historically black academic health center dedicated solely to educating minority and other health professionals. True to its heritage, it is a United Methodist Church affiliated institution. The College is particularly well known for its uniquely nurturing, highly effective educational programs; emerging preeminence in health disparities research; culturally sensitive, evidence-based health services and significant contribution to the diversity of the nation's health professions workforce. Diverse Issues in Higher Education's ranking of institutions annually lists Meharry as a leading national educator of African Americans with M.D. and D.D.S. degrees and Ph.D. degrees in the biomedical sciences.

We focus on understanding molecular and genetic basis underlying functional crosstalk between T lymphocytes and natural killer (NK) cells in various patho-physiolological conditions. Our pioneering work in solid tumor models showed that activated CD8 T cells provide a necessary “help” to dormant intratumoral NK cells in eliciting their effector function to cause complete regression of tumor, including antigen-deficient tumor escape variants (J Immunol 2007; Immunology 2010). Altered phosphorylation of multiple signaling proteins during CD8 T–NK interaction suggests a cellular remodeling allowing acquisition of T cell central-memory and NK cell effector/regulatory phenotypes. In breast cancer patients also, molecular signatures associated with NK cell activation predicts relapse-free survival (J Transl Med 2013). Our translational efforts are thus directed at optimizing adoptive T cell/NK cell therapy by various strategies, including the proteasome inhibitor bortezomib, Notch ligands, and neurotransmitters in breast, kidney and lung cancers. We find that bortezomib treatment in mice bearing solid tumors provides host survival benefit by amplifying tumor cell caspase-8 activation (JNCI 2008), enhancing CD8 T cell effector molecules via increased Notch-NFkB crosstalk (Oncotarget 2015) and improving FasL-mediated tumor cell lysis following adoptive cell transfers (Cancer Res 2015). In collaboration with Drs David Carbone and Mikhail Dikov, we show that Notch-1 activation in CD8 T cells by Delta-like Notch ligand DLL1 cluster enhances their anti-tumor function and memory in EGFR-resistant inducible lung cancer models (Cancer Res 2011 & 2015). Using various intravital imaging tools in mouse models, our current studies are digging deeper into lymphocyte processes that could help us identify immunogenetic signatures to provide insights on novel combinatorial immune strategies, which are lymphocyte-stimulatory and capable of overcoming cancer-associated immunosuppression.