Introduction

Our group is interested in establishing the long-term outcomes in women treated for breast cancer and the molecular correlates of these outcomes. We have been the recipient of two 10-year philanthropic grants that have enabled such long-term un-interrupted activity. We have established a state-of-the-art molecular diagnostics lab with a full range of molecular platforms including Next-Gen-Sequencing.

We have assembled a cohort of 460 women with confirmed breast cancer who were recruited at first presentation between 2008 and 2013. These women have been followed-up over the past 7 years. Our loss to follow-up rate of 2% is unmatched outside the clinical-trial setting for such a large number over such a long period. The complete clinical history along with formalin fixed tumor specimens as well as matched blood specimens for most of the patients in the cohort have been archived at the St. John’s Research Institute. The median follow-up as of September 2016 has reached 66 months.

Our research is focused on the investigation of structure function correlation of physiologically important protein molecules and their relation to disease. We are interested in various medical conditions such as hemoglobinopathies, thalassemia, iron deficient anemia, multiple sclerosis, neurodegenerative disorders and depression. The major biophysical techniques used by the group include absorption and emission spectroscopy and mass spectrometry. To screen the clinically important biomarker in the biological fluid, we use mass spectrometry based proteomics. In addition, we are also involved in the discovery of diagnostic tools using mass spectrometry. The group collaborates with Indian Institute of Science in Bioinformatics and Molecular Modeling research.

Our group is involved in understanding the Pediatric Kidney Diseases Nephrotic Syndrome, Acute Kidney Injury. Chronic Kidney Disease and Congenital Anomalies of Kidney and Urinary tract. Our interest is to understand the fundamental genetic mechanisms, molecular and immunological factors involved in the development of kidney disease. For this purpose, we are using various high throughput techniques such as Next-Generation Sequencing, MAGPIX-based multi-analyte detection, flow cytometry analysis of immune cells, immortalized podocyte cell based assays, immunofluorescent assays, etc., to understand the disease progression, identify biomarkers and molecular signatures for prognosis, diagnosis and patient stratification. Out ultimate aim is to translate the research data for clinical setting.

Patterning of developing embryos requires signaling via different molecules in spacio-temporally regulated manner. Hedgehog is one such highly conserved signaling protein required for embryonic patterning and is also hyper-activated in several cancers. Mechanism of Hedgehog release, transport and reception to activate different target genes for tissue patterning and cancer progression involves intricate processes at molecular and cellular levels. Several evidences including our previous work suggest that Hedgehog proteins are secreted on exovesicles. We find that Hedgehog proteins are secreted on at least two types of exovesicles with distinct proteins and miRNAs. Apart from exovesicles, there are other reported extracellular forms of Hedgehog proteins. However, currently the need for secretion of Hedgehog in different extracellular forms remains unclear.

Our group is interested in probing the basic biology of exovesicular release of Hedgehog and miRNA packaging. We are also seeking clarity on the physiological implications of the associated proteins and miRNAs on Shh function during tissue patterning as well as in diseases such as cancer where exovesicles-mediated tumor-stroma interactions have critical implications for tumor progression or regression.