Photo of Irina  Bezsonova, Ph.D.

Irina Bezsonova, Ph.D.

Assistant Professor, Department of Molecular Biology and Biophysics
Academic Office Location:
Molecular Biology and Biophysics
UConn Health
263 Farmington Avenue
Farmington, CT 06030
Phone: 860-679-2769
Fax: 860-679-3408
Email: bezsonova@uchc.edu
Website(s):

Lab Website

Molecular Biology and Biochemistry Program

Education
DegreeInstitutionMajor
M.S.Moscow State University Bio-organic Chemistry
Ph.D.University of TorontoStructural Biology

Post-Graduate Training
TrainingInstitutionSpecialty
FellowshipInternational Soros Science Education ProgramOutstanding achievements in the study of science
M.S. Studies Institute of Bioorganic Chemistry RASMember, protein engineering group of Dr. A.A. Schulga in the NMR laboratory of Prof. A.S. Arseniev
FellowshipMoscow State UniversityOvchinnikov fellowship for outstanding graduate students in biochemistry
FellowshipCanadian Institutes of Health Research (CIHR) Training Program in Protein Folding
PostdoctoralStructural Genomics ConsortiumPost-doctoral studies in the laboratory of Dr. C.H. Arrowsmith

Awards
Name of Award/HonorAwarding Organization
Usp7 - a potential drug target for treatment of cancer.CT Department of Public Health, Biomedical Research Fund
Child Health Research AwardCharles H. Hood Foundation
Post-doctoral Fellowship Award (declined)CIHR - Canadian Institute of Health Research

MEDS5327.402011F: Logic of Modern Biology: Fall 2011

Name & DescriptionCategoryRoleTypeScopeStart YearEnd Year
UConn Health - American Association of University ProfessorsProfessional/Scientific Organizationmember of CBCUConn HealthUniversity20152016
American Society for Biochemistry and Molecular BiologyProfessional/Scientific OrganizationmemberExternalNational20132016
North Eastern Structure SymposiumWorkshop/ConferenceChairOtherRegional20132013
Molecular Biology and Biochemistry Graduate Admissions CommitteeOtherMemberUConn HealthUniversity20122012
American Heart AssociationProfessional/Scientific OrganizationmemberExternalNational20122013
American Association of Cancer ResearchProfessional/Scientific OrganizationmemberExternalNational20112012
PARTNERSHIP FOR EXCELLENCE IN STRUCTURAL BIOLOGYProfessional/Scientific OrganizationmemberOtherRegional20102016

Ubiquitination and Cancer:
The p53 signaling pathway is a complex multi-component network central to cancer biology. Over 50% of all tumors have mutated tumor suppressor p53. The primary focus of my reasearch is structural and biochemical characterization of proteins and protein complexes of p53 pathway, especially, proteins responsible for maintenance of an appropriate level of p53 in the cell such as E3 ubiquitin ligase Hdm2 and ubiquitin-specific protease USP7. We use structural biology tools, NMR spectroscopy and X-ray crystallography, in conjunction with other biophysical and biochemical methods to determine 3D structures of proteins and characterize their interactions with specific binding partners. Detailed knowledge of protein structure provides the basis for rational design of new drugs suitable for anti-cancer therapies.


Ubiquitination and Epigenetics:
Epigenetic marks work as molecular switches that regulate expression of our genes without altering the DNA sequence itself. It is through epigenetic marks that environmental factors like diet, stress and prenatal nutrition can make an imprint on genes that is passed from one generation to the next. These marks include modifications of histone tails (methylation, acetylation, phosphorylation, ubiquitination, etc) and DNA methylation. Ubiquitination of residue K119 of the histone H2A, for example, is a hallmark of stably repressed developmental genes in stem cells and inactive X-chromosome.


We study Polycomb Repressive Complexes PRC1 and PRC2 responsible for developmental gene suppression and maintenance of “stemness” of a cell. PRC2 and PRC1 are multi-protein enzymatic complexes that methylate histone H3 and ubiquitinate histone H2A resulting in stable gene silencing. We are interested in structural organization of these complexes and molecular mechanism of gene recognition and gene silencing by these multi-subunit repressors.

1. Role of ubiquitination in cancer:Ubiquitin Specific Protease 7 (USP7) is a major regulator of the level of Tumor Suppressor p53 in the cell. USP7 stabilizes p53 in response to cellular stresses such as DNA damage and oxidative stress leading to cell cycle arrest and apoptosis, thus preventing damaged genetic material from proliferating.


We use structural biology methods such as Nuclear Magnetic Resonance (NMR) spectroscopy and X-ray crystallography in conjunction with other biochemical and biophysical techniques to study molecular mechanisms underlying USP7 catalytic activity and specificity towards its substrates.


Detailed knowledge of protein structure will provide basis for rational design of new highly specific drugs suitable for anti-cancer therapies.


2. Ubiquitination as an epigenetic mark:


Epigenetic marks work as molecular switches that regulate expression of our genes without altering the DNA sequence itself. It is through epigenetic marks that environmental factors like diet, stress and prenatal nutrition can make an imprint on genes that is passed from one generation to the next. These marks include modifications of histone tails (methylation, acetylation, phosphorylation, ubiquitination, etc) and DNA methylation. Ubiquitination of residue K119 of the histone H2A, for example, is a hallmark of stably repressed developmental genes in stem cells and inactive X-chromosome.


We study Polycomb Repressive Complexes PRC1 and PRC2 responsible for developmental gene suppression and maintenance of “stemness” of a cell. PRC2 and PRC1 are multi-protein enzymatic complexes that methylate histone H3 and ubiquitinate histone H2A resulting in stable gene silencing. We are interested in structural organization of these complexes and molecular mechanism of gene recognition and gene silencing by these multi-subunit repressors.

Accepting students for Lab Rotations: Fall '17, Spring '18

Journal Articles

Title or AbstractTypeSponsor/EventDate/YearLocation
Structural characterization of the interaction between Ubiquitin Specific Protease 7 and Icp0 from HSV1 virusPoster12th North Eastern Structure Symposium2015UConn, Storrs, CT
Hijacked by a Virus: Structural Insights into Substrate Specificity of Ubiquitin Specific Protease 7 (USP7)TalkAuremen 15th Nuclear Magnetic Resonance Users Meeting2015Angra dos Reis, Rio de Janeiro, Brazil
Structural characterization of the interaction between Ubiquitin Specific Protease 7 and Icp0 from HSV1 virus.Poster56th Experimental NMR Conference2015Pacific Grove, CA
Structural insight into the mechanism of USP7 autoregulationPosterWesleyan University Molecular Biophysics Program2015Middletown, CT
Structural insight into the mechanism of USP7 auto-regulationPosterUConn Health, Molecular Biology and Biophysics2015Bristol, CT
Structural and functional characterization of C-terminal region of Ubiquitin-Specific Protease 7Poster54th Experimental Nuclear Magnetic Resonance Conference (ENC)2013Pacific Grove CA, USA
Solution NMR structure of Rev1 C-terminal domain and its complex with Pol(eta) peptidePoster The 9th Annual North Eastern Structure Symposium NESS 20122012Farmington, CT
Solution NMR structure of Rev1 C-terminal domain and its complex with Pol(eta) peptidePosterMMSB Retreat2012Farmington, CT
Ubiquitin-like Domains: from Cancer to EpigeneticsTalkInauguration of the 'Science without Borders' project2012Federal University of Rio de Janeiro, Brazil
Solution NMR structure of Rev1 C-terminal domain and its complex with Pol(eta) peptidePoster53rd Experimental Nuclear Magnetic Resonance Conference (ENC)2012Miami, FL, USA
NMR studies of interactions between mutagenic translesion synthesis DNA polymerases Rev1, pol(eta) and pol(zeta)Poster53rd Experimental Nuclear Magnetic Resonance Conference (ENC)2012Miami, FL, USA
NMR studies of interactions between mutagenic translesion synthesis DNA polymerases Rev1, pol(eta) and pol(zeta)PosterThe 9th Annual North Eastern Structure Symposium NESS 20122012Farmington, CT
Solution structure of PHD domain from human SHPRH and its interaction with methylated histonesPosterThe 9th Annual North Eastern Structure Symposium NESS 20122012Farmington, CT
USP7 C-terminal Region is a Potential Drug Target in Pediatric NeuroblastomaPosterThe 9th Annual North Eastern Structure Symposium NESS 20122012Farmington, CT
USP7 C-terminal Region is a Potential Drug Target in Pediatric NeuroblastomaPosterHood Foundation Scientific Poster Session and Dinner2012Boston, MA
NMR studies of Usp7 - regulator of p53 tumor suppressor and more...TalkMMSB retreat2011West Hartford, CT