Georg Wondrak, PhD

Redox Drug Discovery Targeting Human Skin Cancer

 

My drug discovery research program examines the pathological role of reactive oxygen ('ROS') and reactive carbonyl species ('RCS') in skin carcinogenesis and aims at targeting these reactive intermediates using novel reactivity-based therapeutics for photo-chemoprevention and cancer chemotherapy. In contrast to structure-based approaches that target macromolecules by selective ligands, reactivity-based drug discovery uses chemical reactants such as small molecule catalytic antioxidants, redox cyclers, and carbonyl scavengers as therapeutics that target reactive chemical species involved in human pathology. Three synergistic research projects are currently pursued in the Wondrak laboratory:

 

I. Targeting Metabolic Control of Melanoma Cell Survival.
We are currently testing the hypothesis that the glycolytic control of melanoma cell survival is mediated by methylglyoxal (MG)-adducted heat shock protein 27 ('MG-Hsp27'), a novel therapeutic target amenable to small molecule modulation by specific MG-antagonists ['carbonyl scavengers'].

 

II. Targeting the Redox Achilles Heel of Melanoma.
We are aiming at drug discovery and target identification of experimental redox chemotherapeutics with anti-melanoma activity in vitro and in vivo ['prooxidant redox modulators'].

 

III. SPA-Inducers for Photo-chemoprevention of Skin Cancer.
We are aiming at the design of small molecule biological response inducers as pharmocological activators of the innate skin photo- adaptive response ('SPA'). ['Nrf2 activators' and 'heat shock response inducers'].