We are looking for postdocs (fresh graduates) and research assistants in 2018. Candidates with excellent track record in cancer biology and expertise in mouse experiments are encouraged to apply
Our research is focused on questions related to cancer therapeutics. Cancer is a complex disease and the malignant phenotype involves extensively rewired pathways for growth advantage and survival due to multiple genetic and epigenetic changes. The complexity of alterations in cancer presents a daunting problem with respect to treatment: the malignant process involves multiple aberrant compensatory signaling routes that bypass the inhibition of individual. In addition, cancer is a genetic moving target capable of mutating into resistant or more aggressive forms. Thus, a key to successful therapy is to identify the critical nodes in the oncogeneic network and to target them to reverse cancer phenotypes by inducing apoptosis, senescence and differentiation. In order to generate this system failure in cancer, the most effective approach is probably through the combinational application of a relatively small number of drugs through system perturbation.
We are leveraging various technologies to understand the fundamental questions concerning cancer cell death and survival. Integrating functional genomics, chemical combinations and molecular biology, we are exploring systems biology approach to identify key elements that are critical to a relevant biological phenotype, to identify synthetic lethal gene-gene interactions and to develop novel strategies for cancer therapy.
Damage Response, Cell Cycle Checkpoint and Apoptosis:The majority of therapeutic agents cause DNA damage response, leading to activation of cell cycle checkpoint or apoptosis. Understanding the signals and mechanisms leading to apoptosis or resistance to apoptosis may allow the development of better regimens for the treatment of cancer. Using both genomics mapping and chemical screening approaches, as well as in collaboration with our technology group, we are interested in identifying the key gene modules that are associated with anticancer drug response and deciphering molecular mechanisms of activity of their products as potential targets for therapeutic modulation (J Bio Chem., 2004, Cancer Res. 2005, Cell, 2006, Cancer Res. 2007, J Bio Chem., 2009).
Novel Therapeutic Approaches Targeting Cancer Epigenetic Processes:My laboratory is also interested in pharmacologic modulation of epigenetic processes in cancer. In particular, we are studying the oncogenic Polycomb-mediated gene silencing activity in cancer and its interplay with histone deacetylation and DNA methylation. We are also developing novel chemical approaches that target histone modifications such as histone methylation and deacetylation, leading to interventions of key cancer pathways and efficient apoptosis induction. We have discovered DZNep and its anlogous as a new class of chromatin modifiing compound that have therapeutic potential (PNAS, 2005; J Bio Chem., 2006, Genes & Devel., 2007, Cancer Cell, 2008, Genes & Devel., 2009, Cell Death and Differentiation, 2009)