Nupur P.

Summary of my research Interests: Many a genetically complex diseases such as cancers have ineffective chemotherapeutic treatment options. Decades of research has gone into determining the cause of each different type of cancer, and develop therapies to effectively treat them. However, it is well recognized that diets rich in green leafy vegetables and hence diet derived phyto-nutrients influence disease development. I am interested in developing a preventive strategy to minimize cancer occurrence. I think that a knowledge based useful dietary regimens for enhancing the efficacy of current therapies will better outcomes for patients.

To address these concerns my lab currently focuses on autophagic cell death, a highly regulated PCD pathway, regulated by kinase mammalian target of rapamycin (mTOR; also known as FRAP1), mediated by complex intracellular membrane/vesicle reorganization and lysosomal activity. It can either be involved in the turnover of long-lived proteins and whole organelles in a generalized manner or can specifically target distinct organelles (mitochondria, endoplasmic reticulum) imposed by limiting metabolites. Although autophagy mostly allows cells to adapt to stress, massive autophagy can also kill cells. Various phytonutrients affect autophagy and apoptosis in cell culture cancer model such as ovarian cancer. To determine the contribution of each of these mechanisms by which cruciferous vegetables might be utilized to decrease ovarian cancer risk and used as ligands that enhance the efficacy of current day therapies.

The genetic variation in cell lines are often unknown confounding applicability of results: Our preliminary analysis of the EOC and prostate cancer (PCa) cell lines (GST variants unknown), treated with SFN in a time course of varying SFN doses showed 1) varying sensitivity of cells to SFN close to physiologic concentration ( ≤ 10 µM/L); 2) varying induction of key autophagy marker mRNA and proteins; and 3) differences in HDAC inhibition timing and extents. Further we determined that beclin-1, an autophagy essential protein, may be a key molecule targeted by SFN with si-RNA screen. As GST SNPs in EOC may create metabolic deficits, it is reasonable to investigate whether the interaction of known GST SNPs alter SFN mediated HDAC inhibition and PCD signatures to impact cell survival in vitro. If successful we will inform future studies aimed at developing personalized diets to enhance the health of women who might reliably benefit from an individualized dietary strategy to help prevent disease and prolong health through dietary intervention.

Our overall working hypothesis is that genetic variation (e.g.in SFN metabolizing GST genes) may affect SFN mediated HDAC inhibition leading to measurable PCD signatures in benign and cancer cells. We further hypothesize that SFN induced beclin-1 is the key molecular basis of PCDII induction, and communication between PCDI and II through PI3K-Akt-mTOR pathway.