Currently the research in the laboratory of genetics consists of cancer genetics, inflammation, and cell and gene therapy:
Cancer Genetics: Using viral vectors we have generated mouse models of human glioblastoma multiforme (GBM), non-small cell lung cancer, and prostate cancer. In these models, activation of oncogenes or inactivation of suppressor genes is carried out in a few cells, in immune competent mice, which mimic the human tumors faithfully. We now believe that GBMs are so lethal because the transduced differentiated cells undergo conversion to pluripotent stem cells, which can continue to replicate. Thus as few as ten cells can lead to formation of GBMs. These novel models led us to the discovery of transdifferentiation of GBM cells to blood vessels.
More recently, we have also uncovered that the primary function of the suppressor gene BRCA1 is to keep the integrity of heterochromatin. In BRCA1 mutants, the satellite DNAs are transcribed leading to genomic instability and cancer.
Inflammation: In mouse models of lung cancer, suppression of inflammatory gene products can slow the progression of disease. We have identified the specific sets of target genes involved in this suppression.
We are also interested in studying the molecular mechanisms of how glucocorticoids suppress inflammation. Towards that goal we have recently made the intriguing observation that steroid suppression of inflammatory genes induced by NFkB is dependent on p53. We are also interested in studying the role of inflammation in diabetes and Alzheimer’s Disease.
Cell and Gene Therapy: We have designed unique viral vectors capable of generating iPS cells from a wide variety of normal and diseased somatic tissues. We are generating protocols to convert iPS cells into hematopoietic stem cells, and hepatocytes to correct a variety of genetic and acquired diseases. We are also trying to understand the basic mechanisms of pluripotency and differentiation.