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Singh Lab

Adhesion Signaling and Cancer Therapeutics

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Investigator / Contact Person Mahendra Singh

Research

1. I discovered a novel protein HEPL, also known as CASS4 as the 4th member of the CAS protein family. In this work, I demonstrated a direct interaction between CASS4 and FAK and how this interaction between these two signaling proteins regulates cellular adhesion and metastatic behavior of cancer cells. My long-term goal is to parse out the regulatory role of CASS4 in the metastasis pathways in the context of other CAS proteins, by developing various model systems including animal model for deregulated CASS4 expression.


2. I, along with others, helped establish NEDD9 as a cancer cell-intrinsic protein that contributes to mammary tumor development in the MMTV-PyMT mouse model. My study provides the first in vivo evidence of a role for NEDD9 in breast cancer progression, and suggests that NEDD9 expression may provide a biomarker for tumor aggressiveness.


3. I demonstrated that constitutive absence of an adapter protein NEDD9/HEF1 in a genetic mouse model of mammary tumors induced defects in cell cycle associated with reduced function of Aurora Kinase A and a more aggressive tumor phenotype. The absence of NEDD9 also caused a persistent deficiency in Src activation and influences the susceptibility of mammary cancer cells to dasatinib, a drug targeting Src kinase which demonstrates the potential of NEDD9 as a biomarker for clinical response.


4. I identified a novel polymorphic variant of apolipoprotein B as a genetic predisposing factor associated with gallbladder cancer (GBC) and provided one of the first evidences as to how a single nucleotide polymorphic variant (not a mutant) increases the risk for developing GBC which is the commonest malignancy of the biliary tract worldwide in individuals. I also reported mutation of K-ras oncogene in about one third patients with GBC, first report of its kind from India where GBC is 3rd most common gastrointestinal malignancy.