Current therapeutic options for the majority of advanced cancers remain inadequate, highlighting the need for discovery of new anticancer agents directed against novel targets. The department's mission is to investigate the effectiveness of cancer chemotherapeutic agents in order to develop novel molecular-targeted cancer therapies. We study drug mechanisms in DNA damage and repair, signal transduction and DNA synthesis. In addition, we seek to understand mechanisms of drug resistance. Understanding these mechanisms allows us to design more effective drugs.
We continue to expand our clinical research in pharmacokinetic, pharmacodynamic and, more recently, pharmacogenomics studies of investigational drugs, which enable us to obtain a clear picture of how these drugs impact the patient. The department aims to bridge the gap between the development of promising new drugs and their application in the clinic.
Precise regulation of cellular signaling is important for cell growth and proliferation, cell metabolism and apoptosis; dysregulation of cell signaling can lead to the development of cancer. Cancer therapeutics targets theses alterations in intracellular and intercellular signaling. In our department, we study Cancer metabolism, Signal transduction and Epigenetics, and Tumorigenesis and progression.
Understanding how cancer advances by altering cell metabolism. Tumorigenesis is often associated with altered nucleotide metabolism, characterized by dysregulated Ribonucleotide Reductase (RR), and altered carbohydrate metabolism, characterized by increased glucose uptake and elevated lactic acid production under aerobic conditions. Notably, it was recently reported that RRM2B, the small subunit of RR, serves a crucial role in maintaining chromosomal stability and preventing chronic inflammation-associated tumorigenesis. We are also focused on understanding the autophagy regulatory mechanisms and biological functions in cancer. Autophagy is cell catabolic process in response to stress. Special emphases are focused on the involvement of ROS and oxidative stress from mitochondria to induce autophagy.
Understanding how cancer cells survive against therapeutics by altering cell signaling. Original DNA damage & Repair, add Ub and SUMO.
Understanding how cancer progresses by promoting cell survival. We are investigating how changes in androgen receptor (AR) signaling cause prostate tumorigenesis as well as progression from androgen-sensitive to castration-resistant prostate cancer. In conjunction, we are developing drugs that inhibit AR signaling by novel mechanisms.
Once target molecules are identified and promising drug candidates are selected, it is crucial to understand the clinical pharmacology of the compounds, that is, how they behave in actual patients. Key research areas within Clinical Pharmacology include pharmacokinetics (the study of drug disposition), pharmacodynamics (drug effects) and pharmacogenomics - the study of genetically inherited determinants of drug response and toxicity.
Molecular pharmacology department uses sophisticated techniques such as computer modeling to identify novel therapeutic targets, e.g., receptors, in cancer. This enables our researchers to design new compounds as well as screen leading drug candidates, such as natural products, from our drug screening program that fit the mechanism of action dictated by the specified molecular target. This process is called target validation.
Translational research involves conducting pre-clinical studies on experimental drug therapies and post-clinical analyses on clinical samples. Laboratory-based investigations examine at the molecular level the mechanisms of action and resistance of anticancer agents, including both novel and traditional chemotherapeutic drugs, immunotherapeutics and combinations of anticancer agents and antibodies. The lab helps to facilitate communication between scientists and clinicians studying molecular genetic responses of cells to potential therapeutic compounds, as well as to identify and/or develop biomarkers for targeted therapy.
