Dr. Nagendra NingarajAragen Lifesciences, USA
Title: KCNMA1vE22, a predictive biomarker of breast cancer metastasis to brain
Nearly 30% of women with breast cancer develop brain metastasis with greater risk of mortality. Early diagnosis of brain metastasis of systemic cancers is presently not available. A major impediment for effective treatment of brain metastasis is lack of validated brain specific metastatic biomarkers and difficulty in obtaining brain tumor biopsies from breast cancer spreads in the brain. Recent studies found biomarkers that specifically mediate breast cancer metastasis to brain. We and others have shown that KCNMA1 is overexpressed in breast cancers that metastasize to brain. Evidence indicates that alternative or aberrant pre-mRNA splicing resulting in protein isoforms with diverse functions occur during the development, progression, and metastasis of breast cancer. We identified a hitherto unknown KCNMA1 splice variant KCNMA1vE22, which has a deletion of 108 bp in exon 22. This variant seems to be expressed mostly in metastatic breast tumor cells and in breast cancer metastatic clinical samples. Our in vitro and in vivo findings suggest that the KCNMA1 and BKCa channel protein are overexpressed in breast cancer cells metastatic to brain. Perhaps the discovery and validation of brain specific metastasis associated KCNMA1 alternate splice variants may serve as a new tool for diagnosis, classification, and treatment of breast cancer patients with high risk of brain metastasis
Dr. Nagendra has held progressive leadership roles in pre-clinical and clinical oncology research and development. He worked at academic centers like-University of Kansas, Cedars-Sinai Medical Center, Mercer University Medical Center, Vanderbilt University Medical center, and Anderson Cancer Institute. He led research teams on brain tumor and breast cancer biology. He had extensively published in peer-reviewed journals and secured US, EU, and Japan patents. He directed the Human Tissue banking and biorepository and New Animal Facility. He worked in pharmaceutical companies such as Dr. Reddy’s Labs, Scintilla BioMarc, PPD/ Thermo Fisher Scientific with a focus on in vitro diagnostics, clinical pharmacology and toxicology, medicinal chemistry aspects of clinical drug development. He is presently a Global Senior Director of Scientific Affairs at Aragen Life sciences, USA.