Our Science – Luo Website
Ji Luo, Ph.D.
Research in the Luo lab aims to understand the genetic mechanisms underlying oncogenesis and to identify new therapeutic approaches for cancer treatment. In particular, we are interested in understanding the biology of cancer driven by the Ras oncogene and identifying new therapeutic approaches to treat tumors with Ras mutations.
Synthetic lethal analysis of the KRAS oncogene:
Using isogenic cell lines that contain either wildtype or mutant KRAS alleles, we carried out a genome-wide RNAi screen to identify synthetic lethal interactions with mutant KRAS. This screen yielded a number of candidate genes whose knockdown selectively impaired the viability of KRAS mutant cells. In particular, we have identified genes that are involved in mitotic progression, protein stability control and RNA metabolism that show synthetic lethal interactions with mutant KRAS. Our current effort is focused on elucidating the molecular mechanisms by which these genes support Ras-driven oncogenesis.
Exploring non-oncogene addiction for cancer therapy:
Our RNAi analysis of Ras synthetic lethality indicates that most of the Ras synthetic lethal genes are not mutated in cancer. Thus in addition to 'oncogene addiction', cancer cells also exhibit addiction to a broad network of 'non-oncogenes' that act to alleviate oncogenic stress and enable cancer cell survival. Drugs that explore 'non-oncogene addiction' should provide a new avenue to target cancer cells. We are actively engaged in studying bioactive molecules and developing small-molecule inhibitors that target genes involved in non-oncogene addiction to assess their potentials in cancer therapy.
Genetic Dissection of Cancer using RNAi:
The rapid development in RNAi technology is transforming genetic analysis in human cancer. We are developing new RNAi approaches to enable gene replacement and genotype toggle switches in human cell lines to address basic problems concerning the mechanisms of oncogene addiction and tumor suppression. We are also developing new gene expression and RNAi vectors that allow the introduction of complex genetic alternations in cells to better model the genetic complexities seen in human cancer. In particular, we aim to develop isogenic cell lines with different combinations of oncogenic lesions to study how they differ in malignant phenotype, gene expression, signal transduction and sensitivity to targeted therapies.
To inquire about potential job openings in the lab, please e-mail a cover letter and CV to Dr Ji Luo.
This page was last updated on 6/7/2013.