Eugene Valkov, D.Phil.
- Center for Cancer Research
- National Cancer Institute
- Building 560, Room 11-83C
- Frederick, MD 21702
- +1 (301) 846-1823
- eugene.valkov@nih.gov
RESEARCH SUMMARY
What determines the fate of mRNA at the end of the gene expression pathway? Our approach to exploring this question involves studying reconstituted systems through biochemistry and structural analysis. This strategy allows us to formulate detailed models of the interactions and mechanisms involved. We have developed methods for the recombinant production and biochemical characterization of numerous human factors and complexes crucial to regulating mRNA. Our tools include high-resolution imaging by cryo-EM and computational approaches using machine learning, complemented by thorough biochemical validation of interfaces and biophysical measurements of affinity, stoichiometry, and kinetics of interactions. While our research focuses on fundamental biological phenomena, which are key to all eukaryotic life, we have begun applying our expertise and unique tools towards assisting the development of the next generation of RNA-based therapeutics for cancer treatment.
Areas of Expertise
Eugene Valkov, D.Phil.
Research
The scientific goal of the laboratory is to study the events that determine the molecular ‘fate’ of mRNA in the cytoplasm. We focus on the mechanisms that regulate the removal of structures that protect mRNA from degradation: the poly(A) tail at the 3′-end, in a process known as deadenylation, and the 7-methylguanylate cap at the 5′-end, or decapping. We wish to understand what determines the specificity of these processes and their integration with other stages of the gene expression pathway.
Our principal approach to studying these molecular events is to reconstitute the relevant regulatory macromolecular complexes from highly purified recombinant components and to study them in vitro. To this end, we employ biochemical assays and biophysical approaches to study the interactions between the components using the instrumentation and facilities available at the Biophysical Resource, part of the Center for Structural Biology. To gain a deeper appreciation of the molecular mechanism, we extensively collaborate with our colleagues at the Center for Structural Biology to determine high-resolution cryoEM structures by single-particle analysis using the data collected on the Titan Krios and Talos Arctica microscopes. Among our recent achievements is the reconstitution of the complete human CCR4-NOT deadenylation complex and the entire network of principal human decapping factors. These unique biochemical tools and reagents enable us to study the 5′-to-3′ mRNA decay pathway with unprecedented precision and control.
To relate biochemical and structural insights to function, we test our derived hypotheses directly in human cells; for example, by complementing different variants in cell lines where the expression of individual molecular factors has been knocked out by CRISPR gene editing. This approach has proved very powerful in validating and mapping interactions in vivo. We use high-throughput short-read sequencing with bioinformatic analysis to survey cellular transcriptome and translatome dynamics. We also employ long-read direct RNA sequencing approaches to study mRNA metabolism using Oxford Nanopore instruments available at the RNA Biology Laboratory. A long-standing goal of the laboratory is to achieve sufficient understanding to rebuild entire functionally-relevant regulatory processes of mRNA decay in a test tube. Such a platform offers a unique toolkit to optimize mRNA-based therapeutics for stability and expression and to introduce new design features to target cancer more effectively.
Relevance to Cancer
Dysregulation of posttranscriptional control contributes to autoimmune disease, neurodegeneration, and especially toward oncogenic transformation. Our research is focused on the fundamental biological discovery, which is vital for progress in addressing urgent challenges of age-related diseases. Improved mechanistic understanding of the turnover and translation of mRNA holds enormous potential to provide immediate new vantage points for therapeutic intervention in tumor progression and metastasis.
Publications
Biography
Eugene Valkov, D.Phil.
Eugene received his bachelor's degree in molecular biology from the University of Portsmouth in the UK, graduating with first-class honors. He then pursued a doctoral degree in molecular biophysics at the University of Oxford. After completing a postdoctoral fellowship in Australia, Eugene returned to the UK to conduct his principal postdoctoral research at the MRC Laboratory of Molecular Biology in Cambridge. There, he studied the molecular mechanisms of mRNA export while working with Murray Stewart and also collaborated with Lori Passmore on structural studies of mRNA decay machinery. In 2014, Eugene joined the Max Planck Institute in Tübingen, Germany, as a staff scientist to work with Elisa Izaurralde. Three years later, in 2017, he was promoted to group leader at the same institute. In 2019, he was recruited as a Stadtman Investigator at the NCI's newly established RNA Biology Laboratory.
Job Vacancies
Who we are
- A basic research laboratory seeking to address outstanding mechanistic questions in RNA biology.
- Part of the NIH Intramural Program, a unique research environment supported by stable, generous core funding.
Among the 250 basic and clinical research labs comprising the Center for Cancer Research, the research division of the National Cancer Institute.
What we offer
- A lab culture that promotes research excellence in a diverse and supportive research team.
- US citizens and permanent residents are recruited via the Cancer Research Training Award (CRTA).
- International applicants are recruited via the NIH Visiting Fellow Program.
- Compensation is the same for CRTA and Visiting Fellows. The CRTA Manual provides all information on stipends and benefits.
- For out-of-state or international trainees, we offer help with moving expenses up to $3,000.
- Collaboration opportunities with leading academic groups and partners in the pharmaceutical/biotech industry.
- Free or subsidized access to world-class core research facilities and instrumentation, such as the Titan Krios G4 cryo-EM.
- Interaction opportunities with exceptional basic scientists and clinicians at the NIH.
- Opportunities to present your work and network at the NIH and international conferences.
- Strong focus on individual mentoring, developing research expertise, acquiring transferable skills, and career development.
Professional assistance and support with J1 or H1 visa applications for international scientists at the Division of International Services.
- Further information about training at the NIH and associated benefits.
Looking to join us?
At the postbaccalaureate level, you will have:
- An excellent GPA in biochemistry, molecular biology, chemistry, or a related science major.
- Enthusiasm for research and science.
- Willingness to learn.
- Demonstrated ability to work in a team.
- Strong organizational skills.
- Some experience in a research lab can be beneficial but not essential.
At the postdoctoral level, you will have:
- An open, sharing approach to research and enthusiasm for team science.
- Desire to make cool discoveries and tackle fundamental questions in RNA biology.
Willingness to think outside the box and step out of your comfort zone.
- A Ph.D. in biochemistry, structural biology, or molecular biology.
First/co-first-author publication or a preprint.
To inquire about opportunities, please email eugene.valkov@nih.gov and include your CV, contact details for 2-3 referees, and a one-page statement describing your research experience and why you want to join the lab.
We also welcome inquiries from prospective graduate students seeking a rotation spot in the NIH Graduate Partnerships Program.
If you are an undergraduate or a high school student, consider joining us via the Summer Internship Program in Biomedical Research.
Team
News
02/2024 - Deadenylation kinetics study with Narry Kim is published in Nature Structural & Molecular Biology.
02/2024 - Tanner joined the lab as a postdoc.
12/2023 - Eugene gave an invited talk at SickKids Hospital in Toronto.
10/2023 - Deadenylation: Methods and Protocols, co-edited by Eugene and Aaron Goldstrohm, is published with chapters by Yevgen and Filip.
09/2023 - Filip was awarded a Postdoctoral Fellowship from the German Research Foundation (DFG) as part of the Walter Benjamin program.
08/2023 - Keiko left the lab to continue her undergraduate studies at the University of Maryland.
08/2023 - Annie and Claire joined the lab as postbacs.
08/2023 - The NIGMS funded our collaborative R01 grant with Aaron Goldstrohm on human Pumilio proteins. The NCI/CCR provided supplementary funding for our requested resources via a unique mechanism that seeks to promote intramural/extramural collaboration.
07/2023 - Cryo-EM structures of NOT1/10/11 complexes are published in Communications Biology.
07/2023 - Jade joined the lab as a postbac and part of the NCI Intramural Continuing Umbrella of Research Experiences (iCURE) program.
06/2023 - Keiko joined the lab as a summer intern.
05/2023 - Filip's study of RBP-directed deadenylation is published in Nucleic Acids Research — part of this work Filip carried out at the NCI.
04/2023 - Leah accepted an offer to join Jan Lowe's lab at the MRC Laboratory of Molecular Biology as a Ph.D. student.
03/2023 - Eugene gave an invited talk at the University of California at Riverside.
03/2023 - Yevgen was among the two students recognized this year with the Center for Cancer Research Outstanding Ph.D. Student Award.
03/2023 - Khadija left the lab to return to her family in Morocco.
12/2022 - Adrianna left to pursue a medical degree at the University of Queensland, Australia.
12/2022 - Yevgen defended his Ph.D. thesis virtually at the University of Tuebingen, Germany, with an overall distinction of Magna Cum Laude.
12/2022 - Eugene gave an invited lecture at the Ohio State University, Columbus, Ohio.
12/2022 - The Current Opinion in Structural Biology collection on Protein Nucleic Acid Interactions (2022), where Eugene served as a Guest Editor, is published.
10/2022 - Eugene gave an invited lecture at Moderna headquarters in Boston, Massachusetts.
07/2022 - Adrianna obtained a Cancer Research Training Award (CRTA) from the NCI Intramural Continuing Umbrella of Research Experiences (iCURE) program.
06/2022 - Eugene gave an invited talk and chaired a session at The Post-transcriptional Control of Gene Expression Conference on RNA Decay in Jupiter, Florida.
06/2022 - Eugene joined the Editorial Board of the Journal of Structural Biology and Journal of Structural Biology: X.
04/2022 - Josh accepted an offer to join the Ph.D. program at Harvard University. After rotating through the program, he joined Jeeyun Chung's lab in the Department of Molecular & Cellular Biology.
02/2022 - Eugene successfully presented the lab's research accomplishments to the NCI/CCR leadership during the Interim Tenure-Track Review.
11/2021 - Wataru was awarded a Postdoctoral Fellowship from the Japanese Society for the Promotion of Science as part of the Kaitoku-NIH program to support his research.
Alumni
Lab Life
Lab retreat at Greenbrier State Park, Maryland, in the spring of 2022.
Lab outing to Brewer's Alley in downtown Frederick to celebrate Yevgen's thesis defense.
Yevgen was very pleased with his Ph.D. hat after the successful defense of his doctoral thesis.
Eugene is part of a sizeable delegation of the NIH intramural community at the annual RNA Society conference in Boulder, Colorado, in June 2022.
Eugene at the FASEB conference on the Post-transcriptional Control of Gene Expression: Mechanisms of RNA Decay in Jupiter, Florida (June 2022).
Late-night discussions at the FASEB meeting in Florida
A 'condensate' of RNA biologists swimming during one of the break sessions at FASEB
Yevgen outside the Moderna headquarters in Boston during a collaborative visit.
Cherry blossom outside our building on Campus in early March 2023.
The fall on campus produces some stunning colors among the trees.
Eugene is giving a talk at UC Riverside in March 2023.