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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Network
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Understanding The Role Of Kindlin-1 loss In The Development Of Squamous Cell Carcinoma (University of Edinburgh lead)
1/10/20 → 30/09/23
Project: Research
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A randomized controlled trial of SFX-01 to improve clinical outcomes in COVID-19 patients (STAR-COVID)
Chalmers, J. & Dinkova-Kostova, A.
1/08/20 → 30/09/22
Project: Research
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Institutional Strategic Support Fund (2016)
Cantrell, D., Dinkova-Kostova, A., Kang, L., Murray, P. & Pearson, E.
1/10/16 → 31/05/23
Project: Research
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Detection of thermal shift in cellular Keap1 by protein-protein interaction inhibitors using immunoblot- and fluorescence microplate-based assays
Dayalan Naidu, S., Dikovskaya, D., Moore, T. W. & Dinkova-Kostova, A., 17 Jun 2022, In: STAR Protocols. 3, 2, 17 p., 101265.Research output: Contribution to journal › Article › peer-review
Open AccessFile2 Downloads (Pure) -
Nrf2 activation reprograms macrophage intermediary metabolism and suppresses the type I interferon response
Ryan, D. G., Knatko, E. V., Casey, A. M., Hukelmann, J., Dayalan Naidu, S., Brenes, A. J., Ekkunagul, T., Baker, C., Higgins, M., Tronci, L., Nikitopolou, E., Honda, T., Hartley, R. C., O'Neill, L. A. J., Frezza, C., Lamond, A. I., Abramov, A. Y., Arthur, J. S. C., Cantrell, D. A., Murphy, M. P. & 1 others, , 18 Feb 2022, In: iScience. 25, 2, 21 p., 103827.Research output: Contribution to journal › Article › peer-review
Open AccessFile14 Downloads (Pure) -
Phenyl Bis-Sulfonamide Keap1-Nrf2 Protein-Protein Interaction Inhibitors with an Alternative Binding Mode
Georgakopoulos, N., Talapatra, S., Dikovskaya, D., Dayalan Naidu, S., Higgins, M., Gatliff, J., Ayhan, A., Nikoloudaki, R., Schaap, M., Valko, K., Javid, F., Dinkova-Kostova, A. T., Kozielski, F. & Wells, G., 12 May 2022, (E-pub ahead of print) In: Journal of Medicinal Chemistry. 19 p.Research output: Contribution to journal › Article › peer-review
Open Access -
Pirin, an Nrf2-regulated protein, is overexpressed in human colorectal tumors
Zhang, Y., Knatko, E. V., Higgins, M., Dayalan Naidu, S., Smith, G., Honda, T., de la Vega, L. & Dinkova-Kostova, A. T., 28 Jan 2022, In: Antioxidants . 11, 2, 15 p., 262.Research output: Contribution to journal › Article › peer-review
Open AccessFile12 Downloads (Pure) -
The isoquinoline PRL-295 increases the thermostability of Keap1 and disrupts its interaction with Nrf2
Dayalan Naidu, S., Suzuki, T., Dikovskaya, D., Knatko, E. V., Higgins, M., Sato, M., Novak, M., Villegas, J. A., Moore, T. W., Yamamoto, M. & Dinkova-Kostova, A., 21 Jan 2022, In: iScience. 25, 1, 19 p., 103703.Research output: Contribution to journal › Article › peer-review
Open AccessFile1 Citation (Scopus)14 Downloads (Pure)
Activities
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Breaking the vicious cycle of oxidative stress – inflammation – cell death by reversible cysteine modifications of Keap1
Albena Dinkova-Kostova (Speaker)
2021Activity: Talk or presentation types › Invited talk
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20th Biennial Meeting of Society for Free Radical Research International
Albena Dinkova-Kostova (Participant)
17 Mar 2021Activity: Participating in or organising an event types › Participation in conference
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23rd International Conference on Oxidative Stress Reduction, Redox Homeostasis & Antioxidants
Albena Dinkova-Kostova (Participant)
15 Oct 2021Activity: Participating in or organising an event types › Participation in conference
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Keap1/Nrf2 as a druggable target
Albena Dinkova-Kostova (Speaker)
2021Activity: Talk or presentation types › Invited talk
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Discovery Days 2018
Jonathan Urch (Organiser), Pete Downes (Chair), John Rowan (Presenter), Sally Ibbotson (Presenter), Glyn Bengough (Presenter), Mary Modeen (Presenter), Karl Leydecker (Chair), Graham Fagen (Presenter), Nikki Doig (Presenter), Faisel Khan (Presenter), Lynn Kilbride (Presenter), Albena Dinkova-Kostova (Presenter), Kevin Grant (Presenter), Wendy Moncur (Presenter), Jacqueline Eccles (Presenter), Thomas McConnachie (Presenter), Kurt Mills (Presenter), Wendy Alexander (Chair), Mark Smith (Presenter), Judith Sixsmith (Presenter), Chris Murray (Presenter), Jennifer Woof (Presenter), Graham Pullin (Presenter), Daniel Cook (Presenter) & Andrew Cook (Presenter)
11 Jan 2018 → 12 Jan 2018Activity: Other activity types › Public engagement and outreach - public lecture/debate/seminar
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