Albena Dinkova-kostova

Biography

Albena T. Dinkova-Kostova obtained her PhD in Biochemistry from Washington State University.  Her doctoral work was on the purification and characterization of enzymes of the phenylpropanoid pathway. During that time she became intrigued by the fact that phenylpropanoids, some of which (podophyllotoxin and the semi-synthetic etoposide and tenoposide) are used in cancer chemotherapy; others (nordihydroguaiaretic acid) are potent antioxidants, are also inducers of anticarcinogenic enzymes. She joined the laboratory of Paul Talalay (Johns Hopkins University) where she became interested in chemoprevention by chemical and dietary induction of cytoprotective proteins.   In 2007 Albena joined the Medical Research Institute, University of Dundee, Scotland as a Lecturer and Research Councils UK Academic Fellow.  Her work on the mechanism of induction of cytoprotective proteins (through the Keap1/Nrf2 pathway) and the chemistry of inducers has been published in Biochemistry, Cancer Prevention Research, Chemical Research in Toxicology, Chemistry & Biology, Journal of Biological Chemistry, Journal of Medicinal Chemistry,  Methods of Enzymology, and the Proceedings of the National Academy of Sciences USA. It has been highlighted in commentaries and attracted more than 5000 citations.  She is the recipient of the 2011 Arthur C. Neish Young Investigator Award of the Phytochemical Society of North America.

Research Interest

The steady increase in the number of new cancer cases diagnosed each year and the modest success in cancer treatment highlight the urgent need for the development of strategies for prevention.  It is important to understand that the disease cancer is the process of carcinogenesis itself that begins many years, often decades, before any clinical symptoms become apparent.  Protection against cancer in animal models can be accomplished by induction of the Keap1/Nrf2 pathway which controls the gene expression of numerous enzymes (e.g., glutathione S-transferases, epoxide hydrolase, quinone reductase 1, heme oxygenase 1) that catalyze versatile reactions collectively leading to detoxification of electrophiles and oxidants.  The expression of Nrf2-dependent genes can be elevated by a wide variety of pharmacological agents termed “inducers”, some of which are present in the human diet.  Inducers react with specific cysteine residues of the sensor protein Keap1, thereby allowing transcription factor Nrf2 to translocate to the nucleus and activate transcription.  The discrete events in the regulation of the Keap1/Nrf2 pathway and the mechanism of action of Nrf2 inducers are a major objective of our research.  We are also investigating the regulation of the heat shock response, another cellular cytoprotective pathway, and the ability of small molecules which can inhibit Hsp90 to interfere with cancer cell proliferation. In addition to biochemical studies in various in vitro and cellular systems, we also employ in vivo models with a focus on models of UV radiation-induced skin carcinogenesis.  The knowledge obtained from these models will allow the design of clinical trials to determine the effectiveness of Nrf2 inducers in preventing the development of skin cancers in high-risk populations, such as solid organ transplant recipients who are at nearly 100-fold increased risk for skin cancer development compared to the general population.