Sergey A. Kozmin Professor

Born Moscow, Russia, 1971.
Moscow State University, Diploma, 1993.
University of Chicago, Ph.D., 1998.
University of Pennsylvania, Postdoctoral Associate, 1998-2000.
University of Chicago, Professor, 2000-present.

Accolades

2008 Magomedov-Scherbinina Memorial Prize, University of Rochester.
2007 Novartis Chemistry Lectureship.
2006 SSOCJ Lectureship Award, Japan.
2005 National Science Foundation CAREER Award.
2005 GlaxoSmithKline Chemistry Scholar Award.
2004 Camille Dreyfus Teacher-Scholar Award.
2004 Amgen Young Investigator's Award.
2004 American Cancer Society Research Scholar.
2003 Alfred P. Sloan Fellow.
1997 Elizabeth R. Norton Prize for Excellence in Graduate.
1993 Diploma with Honors, Moscow State University.

OFFICE: 5735 S. Ellis Ave., SCL 328, Chicago, IL 60637

PHONE: (773)702-6886

FAX: (773)702-0805

E-MAIL: skozmin@uchicago.edu

WEB: http://kozmin-group.uchicago.edu/

CTCMLD: http://ctcmld.uchicago.edu/

RESEARCH INTERESTS:

Molecular Pharmacology

Cell-permeable small organic molecules are useful for dissecting complex metabolic and signaling networks. Such compounds function by modulating the protein activity directly, providing a complementary approach to the widely employed gene replacement and RNA interference strategies. While significant progress toward identification of compounds that regulate many cellular pathways has been made, developing potent and highly specific pharmacological probes remains an important and a highly challenging endeavor. We employ two complementary strategies en route to an arsenal of new pharmacological agents. The first approach relies on natural products as a rich source of pharmacological probes for basic and translational biomedical research. We develop efficient chemical syntheses of such rare compounds and elucidation of their mechanism of action. We have developed a number of natural product analogs that potently and specifically target cytoskeletal organization, eukaryotic protein synthesis and bacterial transcription. The second approach relies on generating and screening new chemical libraries that mimic the structural diversity of secondary metabolome. We are using this strategy to identify an arsenal of new small-molecule tools to study altered energy metabolism in cancer. Due to the increased dependency of tumor cells on glycolysis, and its likely role in promoting cell proliferation, survival and invasion, understanding of the nature of reprogrammed energy metabolism in cancer cells is of significant current interest. This study will help in identifying the underlying reasons for major alterations in energy producing pathways employed by rapidly proliferating cells and will test the possibility of targeting such cells selectively both in vitro and in vivo.

 

New Reaction Discovery

The identification of new reactions expands our knowledge of chemical reactivity and enables new synthetic applications. Accelerating the pace of this discovery process remains challenging. We have been developing highly effective and simple platforms for screening a large number of potential chemical reactions in order to discover and optimize previously unknown catalytic transformations, thereby revealing new chemical reactivity. We have initially used matrix-assisted laser desorption/ionization and time-of-flight mass spectrometry (MALDI–TOF–MS) to analyse chemical transformations on the surface of self-assembled monolayers of alkanethiolates on gold. Despite the high throughput of the primary reaction screen and its ability to detect products with unanticipated structures, subsequent translation of the initially identified interfacial reactions to preparative, solution-phase processes have often required substantial effort.  To address this problem, we developed a new reaction-discovery strategy that features not only excellent screening throughput, but also a highly efficient translation of the initial ‘hits’ into catalytic, synthetically useful transformations. The reactions are rapidly analysed in solution using label-assisted laser desorption/ionization and time-of-flight mass spectrometry (LA–LDI–TOF–MS). This simple and highly effective approach is based on the incorporation of a readily available polyaromatic tag into the structure of a reactant, thereby greatly facilitating the desorption/ionization process and enabling rapid and selective MS analysis of hundreds of chemical reactions in solution under matrix-free conditions with excellent efficiency. After validation of the concept by monitoring the course of several known transformations, the technology was used to evaluate the outcome of 696 different reactant combinations, and led to the discovery of two previously unknown benzannulations.

 

Selected References

Cabrera-Pardo, J.R.; Chai, D. I.; Liu, S.; Mrksich, M.; Kozmin, S.A. Label-Assisted Mass Spectrometry for Acceleration of Reaction Discovery and Optimization. Nature Chem. 20135, 423-427.

Montavon, T.J.; Li, J.; Cabrera-Pardo, J.R.; Mrksich, M.; Kozmin, S.A. Three Component Reaction Discovery Enabled by Mass Spectrometry of Self-Assembled Monolayers. Nature Chem. 20124, 45-51.

Cui, J.; Hao, J.; Ulanovskaya, O. A.; Dundas, J.; Liang, J.; Kozmin, S. A. Creation and Manipulation of Common Functional Groups En Route to a Skeletally Diverse Chemical Library. PNAS  201117, 6763-6768.

Pronin, S.V.; Martinez, A.; Kuznedelov, K.; Severinov, K.; Shuman, H.A.; Kozmin, S. A. Chemical Synthesis Enables Biochemical and Antibacterial Evaluation of Streptolydigin Antibiotics. J. Am. Chem. Soc. 2011133, 12172-12184. 

Ulanovskaya, O. A.; Cui, J.; Kron, S. J.; Kozmin, S. A. A Pairwise Chemical Genetic Screen Identifies New Inhibitors of Glucose Transport. Chem. Biol. 201118, 222-230.

Ulanovskaya, O. A.; Janjic, J.; Suzuki, M.; Sabharwal, S. S.; Schumacker, P. T.; Kron,S. J.; Kozmin, S. A. Synthesis enables identification of the cellular target of leucascandrolide A and neopeltolide. Nature Chem. Biol. 20084, 418-424. 

Statsuk, A. V.; Bai, R.; Baryza, J. L.; Verma, V. A.; Hamel, E.; Wender, P. A.; Kozmin, S. A. Actin is the Primary Cellular Receptor of Bistramide A. Nature Chem. Biol. 20051, 383-388.