Rakesh K. Srivastava
University of Kansas
Rakesh K. Srivastava is a Professor in Cancer Research and KBA Eminent Scholar in University of Guelph,Canada.
Cancer biology, angiogenesis, metastasis, transgenic animals, stem cells, biomarkers, transcription factors, drug discovery and development The main focus of my laboratory is to examine the molecular mechanisms of apoptosis, angiogenesis and metastasis, and develop novel drugs for the treatment and prevention of various cancers. We have used biochemical, molecular and transgenic animal approaches to identify novel death receptor agonists. These small molecules bind to death receptors and induce apoptosis in cancer cells, while sparing normal cells. Inhibition of survival pathways have been shown to enhance the therapeutic potential of death receptor agonists. We are examining the molecular mechanisms and preclinical potential of natural products and dietary agents such as resveratrol, curcumin, EGCG, sulforaphane, and diallyl trisulphide for the prevention of various cancers. These compounds appear to enhance the therapeutic potential of death receptor agonists. Furthermore, these agents sensitize those cancer cells that are resistant to chemotherapy and radiotherapy alone. Thus, the use of chemopreventive agents may enhance the therapeutic potential of anticancer drugs, irradiation and death receptor agonists. Chromatin modification has emerged as a new fundamental mechanism for gene transcriptional activity and has been associated with many cellular processes like proliferation, growth, apoptosis, and differentiation. It is increasingly recognized that epigenetic modifications constitute important regulatory mechanisms for the pathogenesis of malignant transformations. The role of epigenetics in diagnosis and treatment is likely to increase as mechanisms leading to the transcriptional silencing of genes involved in human cancers are revealed. Drugs that inhibit methylation are used both as a research tool to assess reactivation of genes silenced in cancer by hypermethylation and in the treatment of malignancies. In addition, the molecular mechanisms by which histone deacetylase inhibitors induce changes in gene expression are being examined. Furthermore, the clinical potentials of HDAC inhibitors and death receptor agonists are being evaluated in several models of human cancer. Recent breakthroughs in stem cell biology, especially the development of induced pluripotent stem cell technique, have generated tremendous enthusiasm and efforts to explore the therapeutic potential of stem cells in human diseases. Progress in stem cell research and the identification of potential stem cells provides hope for the use of stem cells in regenerative medicine, treatment and prevention. The goal is to use adult or tissue-restricted stem cells as a possible approach for the treatment of cancer. We are using small molecules to target specific signaling pathways and/or mechanisms in manipulating cell fate and function. These small molecules are starting to play increasingly important roles in both elucidating the fundamental biology of stem cells and facilitating the development of therapeutic approaches. Such approaches could involve cell replacement therapies using homogenous functional cells produced under chemically defined conditions in vitro and the development of small-molecule based drugs for the treatment of human diseases.