2009 © Institute for Molecular Medicine Finland FIMM
Group Kuznetsov
Sergey Kuznetsov received his undergraduate degree from St-Petersburg State University in Russia in 1997. He went on to study evolutionary aspects of immunity and development in the model cnidarian Hydra in the laboratory of Prof. Thomas Bosch at the University of Kiel, Germany.
Upon receiving his Ph.D. in 2002, he began his postdoctoral training in the laboratory of Dr. Shyam Sharan in the Mouse Cancer Genetics Program (MCGP) at the National Cancer Institute, NIH, USA, where he worked on two DNA repair genes Rad51c and BRCA2. He generated a conditional knockout mouse model for Rad51c, which helped to reveal the role for Rad51c in Holliday Junction resolution during mouse meiosis. These mice have also been used to create the first spontaneous cancer model to study the role of Rad51 family genes in cancer. Finally, he also developed a comprehensive in vitro system using mouse embryonic stem cells to evaluate the breast cancer risk for any mutation in human BRCA2 gene.
Sergey Kuznetsov’s research team at FIMM investigates molecular mechanisms of cancer progression. The group aims to identify genes that are critical for development of particular tumor types – genes also known as “drivers” of tumor formation, and distinguish them from “passengers.” To achieve this goal, non-descriptive, functional assays are used. These include high throughput RNA interference (RNAi) screens in cancer cell lines, and forward and reverse genetics approaches in mice. The results are expected to lead to new therapeutic targets and strategies.
Several projects in the group are focused on breast cancer as one of the most common cancer types in women. On the one hand, these are groups of hereditary breast cancer tumors associated with germline mutations in genes such as BRCA1, BRCA2, or CHEK2. Although relatively minor in absolute numbers of affected cancer patients, these tumors are clearly defined by their mutational status in one of these genes. This feature can be used to selectively target mutant cancer cells without harming non-mutated normal tissues. In addition, one project attempts to develop a new in vivo approach that would allow to study any type of breast cancer experimentally. This approach may open unprecedented opportunities to study sporadic breast cancer subtypes for which no appropriate animal models have been developed.
The team also continues to study the Rad51c mouse model to answer the fundamental question of why mutations in ubiquitously expressed DNA repair genes lead to tumors of certain tissues but not others. Based on his late finding that mutations in Rad51c promote tumors in specialized sebaceous glands and suppress p53-specific tumor types, tissue-specific roles of Rad51c are investigated in epithelial tissues in mice. Understanding the mechanisms of tissue specificity in cancer may provide another strategy for treatment of certain cancer types.
Selected publications:
- Kuznetsov SG, Liu P, Sharan SK. Mouse embryonic stem cell-based functional assay to evaluate mutations in BRCA2. Nat Med. 2008 Aug;14(8):875-81.
- Li L, Biswas K, Habib LA, Kuznetsov SG, Hamel N, Kirchhoff T, Wong N, Armel S, Chong G, Narod SA, Claes K, Offit K, Robson ME, Stauffer S, Sharan SK, Foulkes WD. Functional redundancy of exon 12 of BRCA2 revealed by a comprehensive analysis of the c.6853A>G (p.I2285V) variant. Hum Mutat. 2009 Nov;30(11):1543-50
- Philip S, Swaminathan S, Kuznetsov SG, Kanugula S, Biswas K, Chang S, Loktionova NA, Haines DC, Kaldis P, Pegg AE, Sharan SK. Degradation of BRCA2 in alkyltransferase-mediated DNA repair and its clinical implications.Cancer Res. 2008 Dec 1;68(23):9973-81.
- Kuznetsov S, Pellegrini M, Shuda K, Fernandez-Capetillo O, Liu Y, Martin BK, Burkett S, Southon E, Pati D, Tessarollo L, West SC, Donovan PJ, Nussenzweig A, Sharan SK. RAD51C deficiency in mice results in early prophase I arrest in males and sister chromatid separation at metaphase II in females. J Cell Biol. 2007 Feb 26;176(5):581-92.
- Kuznetsov SG, Haines DC, Martin BK, Sharan SK. Loss of Rad51c leads to embryonic lethality and modulation of Trp53-dependent tumorigenesis in mice. Cancer Res. 2009 Feb 1;69(3):863-72
Group Members
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Open positions at the Kuznetsov's lab
One post-doctoral position is available immediately to investigate breast cancer progression mechanisms in a new mouse model
Qualifications for a post-doctoral candidate:
A Ph.D. in genetics, cell biology, or a closely related field is required. Extensive English communication skills and bench level experience with molecular and cell biological techniques and publications in top-tier journals are essential. A practical experience with mammary fat pad transplantation technique and (optional) experience with shRNAs will be strongly preferred. Recent graduates are encouraged to apply.
Job Type: Full time position
Compensation: Salary based on the University of Helsinki salary system
To apply for this position, please send a motivation letter, curriculum vitae, and the contact information for three professional referees including current and former supervisors as a single pdf file to Dr. Sergey Kuznetsov (Email: sergey.kuznetsov@helsinki.fi).
PhD student positions may be available for outstanding candidates.