Projects per year
Personal profile
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 is focused on the mechanism of induction of cytoprotective proteins through the Keap1/Nrf2 pathway, and the chemistry of inducers. Her publications have been highlighted in commentaries and attracted more than 10000 citations. She is the recipient of the 2011 Arthur C. Neish Young Investigator Award of the Phytochemical Society of North America.
Research
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. However, the Keap1/Nrf2 pathway is often upregulated in established tumors, where it contributes to cancer cell survival, metabolic adaptation, chemo- and radioresistance.
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 cutaneous squamous cell carcinoma and colorectal cancer. The knowledge obtained from these models will allow the design of clinical trials to determine the effectiveness of Nrf2 modulators for cancer prevention and treatment in high-risk populations.
Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
Education/Academic qualification
Master of Science, Sofia University St. Kliment Ohridski
Doctor of Philosophy, Washington State University Pullman
External positions
Adjunct Associate Professor, Johns Hopkins University
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Collaborations and top research areas from the last five years
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Advances and challenges in therapeutic targeting of NRF2
Dinkova-Kostova, A. T. & Copple, I. M., Mar 2023, In: Trends in Pharmacological Sciences. 44, 3, p. 137-149 13 p.Research output: Contribution to journal › Review article › peer-review
Open AccessFile23 Citations (Scopus)55 Downloads (Pure) -
Chronic hyperglycaemia increases the vulnerability of the hippocampus to oxidative damage induced during post-hypoglycaemic hyperglycaemia in a mouse model of chemically-induced type 1 diabetes
McNeilly, A. D., Gallagher, J. R., Evans, M. L., de Galan, B. E., Pedersen-Bjergaard, U., Thorens, B., Dinkova-Kostova, A. T., Huang, J-T., Ashford, M. L. J., McCrimmon, R. J. & Hypo-RESOLVE Consortium, Jul 2023, In: Diabetologia. 66, p. 1340–1352 13 p.Research output: Contribution to journal › Article › peer-review
Open AccessFile3 Citations (Scopus)6 Downloads (Pure) -
Inhibition of GSK3 enhances NRF2 stability and nuclear localisation in pancreatic beta cells
Patibandla, C., Van Aalten, L., Dinkova-Kostova, A., Honda, T., McNeilly, A., Hayes, J., Cantley, J. & Sutherland, C., Apr 2023, In: Diabetic Medicine. 40, p. 48 1 p.Research output: Contribution to journal › Meeting abstract › peer-review
Open Access -
Introduction to Special Issue on “Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases”
Cuadrado, A., Dinkova-Kostova, A. T. & Mann, G. E., 1 Feb 2023, In: Free Radical Biology and Medicine. 195, p. 258-260 3 p.Research output: Contribution to journal › Editorial › peer-review
Open AccessFile64 Downloads (Pure) -
NOX4-derived ROS are neuroprotective by balancing intracellular calcium stores
Gola, L., Bierhansl, L., Csatári, J., Schroeter, C. B., Korn, L., Narayanan, V., Cerina, M., Abdolahi, S., Speicher, A., Hermann, A. M., König, S., Dinkova-Kostova, A. T., Shekh-Ahmad, T., Meuth, S. G., Wiendl, H., Gorji, A., Pawlowski, M. & Kovac, S., 21 Apr 2023, In: Cellular and Molecular Life Sciences. 80, 5, 18 p., 127.Research output: Contribution to journal › Article › peer-review
Open AccessFile3 Downloads (Pure)
Prizes
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Global Highly Cited Researchers List 2022
Dinkova-Kostova, Albena (Recipient), 1 Dec 2022
Prize: Other distinction
Activities
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The role of Nrf2 for mitochondrial adaptation in inflammatory macrophages
Albena Dinkova-Kostova (Speaker)
24 Aug 2022Activity: Talk or presentation types › Invited talk
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Targeting KEAP1 with electrophiles and KEAP1-NRF2 protein-protein interaction inhibitors for disease prevention and treatment
Albena Dinkova-Kostova (Speaker)
21 Mar 2022Activity: Talk or presentation types › Invited talk
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Keap1/Nrf2 as a druggable target
Albena Dinkova-Kostova (Speaker)
15 Oct 2022Activity: Talk or presentation types › Invited talk
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The anti-inflammatory activity of transcription factor Nrf2
Albena Dinkova-Kostova (Speaker)
10 Jan 2022Activity: Talk or presentation types › Invited talk
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Nrf2 – Keap1 System
Albena Dinkova-Kostova (Speaker)
21 Sept 2022Activity: Talk or presentation types › Invited talk