Research
  • Mitochondria-to-nucleus communication and its role in breast and other cancers
  • Global response to oxidative stress and its role in breast an other cancers
  • Genetics mechanisms of mitochondria-mediated-nuclear genome instability
  • Oxidative damage and its repair in the nucleus and the mitochondria
With the exception of peripheral red blood cells, mitochondria are present in all eukaroytic cells in varying numbers, from hundreds to thousands. Mitochondria perform multiple cellular function and are the major source of cellular energy and of reactive oxygen species (ROS). It is estimated that human cells produce up to 10 million ROS/mitochondrion/day. In mitochondria, the ROS are formed by the univalent reduction of molecular oxygen that is mediated by reactive compounds such as semi-ubiquinone, which are involved in electron transport chain. ROS cause oxidative stress, mutations, and promote tumor formation and progression. The growth promoting effects of oxidative stress in cancer is due to oxidative stress responsive signal transduction. Oxidative stress is also implicated in aging, and many diseases including heart, lung and neurodegenerative diseases.

The long-term goal of our laboratory is to understand the mechanisms of mitochondria mediated oxidative stress, genomic instability and its role in cancer. Currently, research in the laboratory is focused on identifying pathway(s) that protect cells from mitochondrial oxidative stress and genomic instability of both the mitochondrial and nuclear genomes. We are also conducting experiments to identify genes that are involved in monitoring the functional state of mitochondria and transducing signals from dysfunctional mitochondria to the nucleus (Mitochondria-to-Nucleus communication). These studies employ the unicellular eukaryote Saccharomyces cerevisiae yeast, mouse, and mammalian cell culture model systems to study these processes. Environmental carcinogens, pharmacological and chemotherapeutic agents are used to induce oxidative stress and genomic instability. Our approach uses both molecular and genetic methods in concert: molecular assays are used to detect and characterize genes of interest and in vivo function of the proteins is assessed by genetic analysis. In addition to understanding basic mechanisms, we have taken a multidisciplinary translational approach to identify molecular markers of oxidative stress involved in detection, diagnosis and treatment of cancer and other oxidative stress related diseases.

Described below are the ongoing projects in my laboratory
  1. Genetics of mitochondria-to-nucleus communication in human breast epithelial cells and its role in breast cancer: We have determined the global gene expression profile in response to loss of mitochondrial function in breast epithelial cells. This project investigates the role of identified genes in primary breast cancer.
  2. Genetics of mitochondria-to-nucleus communication in yeast cells: This project investigates the genes and mechanisms involved in monitoring the functional state of mitochondria, the major site of ROS production. We have used cDNA microarray to determine the global gene expression profile in response to loss of mitochondrial function and are currently investigating the pathways that protect cells from mitochondria-mediated nuclear mutator phenotype.
  3. Global response to oxidative stress in Saccharomyces cerevisiae: We have determined the in vivo genetic targets of superoxide induced oxidative stress. We are now investigating the global mechanisms of adaptation to oxidative stress that leads to genomic instability. This project uses genetic and biochemical approaches to identify pathways involved in oxidative DNA damage and repair in the mitochondria and in the nucleus of yeast S. cerevisiae.
  4. Genetic instability in human epithelial cells: Investigates the mechanisms of spontaneous or induced (by carcinogens and cancer therapeutic agents) mitochondrial and nuclear genome mutagenesis in human breast epithelial cell culture model. This project uses genetic and biochemical approaches to define the mechanisms involved in oxidative DNA damage and repair in the mitochondria and in the nucleus of mammary epithelial cells.