Федеральное государственное бюджетное учреждение науки
Институт эволюционной физиологии и биохимии им. И.М. Сеченова
Российской академии наук (ИЭФБ РАН)

Igor M. Rouzine

Igor M. Rouzine

Igor M. Rouzine

Lead Scientist Immunogenetics

Sechenov Institute of Evolutionary Physiology and Biochemistry
Russian Academy of Sciences
44 prospekt Thorez, room 2305
Saint-Petersburg 194223 Russia

E-mail: igor.rouzine@iephb.ru,
ivan4995@gmail.com

Phone: +7 981 194 4938

What do we do: modeling the evolution and immunology of pathogenes

Pathogens evolve rapidly to circumvent drug treatments and immune surveillance, which dramatically impacts public health. Research and treatment are complicated by high genetic diversity of some viruses within and across infected individuals, as well as their complex evolutionary mechanisms, including selection, random genetic drift, and temporal variation in a host environment. Moreover, many pathogens have a large number of linked sites approximately 102 -103 for HIV and hepatitis C virus (HCV) that evolve simultaneously and inter-dependently through two different effects, «epistasis» due to interaction between proteins and signaling network, and co-inheritance linkage («clonal interference»). Our research is focused on developing mathematical tools that predict evolution of pathogens with strong linkage effects, including analytic and computational methods and estimators of evolutionary parameters from sequence data.

modeling the evolution and immunology of pathogenes

Motivation

The last decade has seen explosive progress in mathematical modeling of microbial populations and high-fidelity sequencing. Taking advantage of these developments, my team will address evolution of microbes (yeast, bacteria) and viruses (HIV, influenza, polio, CHIKV, Dengue, HCV). Launching from my previous mathematical and applied studies, we are applying existing methods and models to study the viral evolution under time-dependent conditions, develop new mathematical techniques and improve existing phylogenetic tools, and identify some key factors of HIV pathogenesis. Our multi-disciplinary team fuses the recent mathematical discoveries with multiple-scale modeling and software tools. We are especially interested in the evolutionary effects of epistasis, recombination, and the theory of phylogenetic relationships in the presence of selection and the other factors. The project is designed to create significant clinical impact by fostering research into novel classes of drugs to control viral adaptation rate and achieve viral containment. Our software will facilitate personalized medicine and vaccine design against the pathogens escaping treatment and immune responses. The results are published and diffused in higher education and public presentations.

An example of a recent work

High-fidelity detection method of epistasis from DNA sequence samples
Pedruzzi & Rouzine, PLOS Pathogens 2021


A. The computer model of asexual evolution includes the factors of random mutation, selection, epistasis, and random genetic drift. Pairwise haplotype frequencies are averaged over an ensemble of independent simulation runs (populations). The strength of interactions, UFEij0, is calculated. The indirect links and the residual stochastic linkage disequilibrium are excluded by using triple-site haplotype frequencies, UFEij0.

B. Pre-set epistatic network for 50 sites. Real epistatic links are shown by green lines. The resulting indirect links are red lines. Some examples of stochastic linkage bonds are shown by blue lines. C-D. The network of strong ( UFE > 0.5 ) candidate epistatic interactions predicted (C) from a single population and (D) after averaging over 200 populations.

E. Scatter plot of 3-locus haplotype min(UFEij0) shown against UFEij for the pairs identified in (D). Dashed sector (green): Predicted direct interactions.

F. Predicted network accurately recapitulates the pre-set epistatic network.

Parameters:

  • initial allele frequency 0.45,
  • mutation rate per genome Ub = 0.07,
  • fixed selection coefficient s = 0.1,
  • epistatic strength E = 0.75.

Biography

Before 1995, Igor Rouzine worked in Condensed Matter Theoretical Physics, where he published 27 papers. Then he moved to the theory of evolution, application to viruses, and immunology of pathogens. Combining the methods of theoretical physics, population genetics, and epidemiology, he models mathematically the evolution, dynamics, and immunology of viruses. The aim is to understand and predict, with a mathematical precision, the systemic interaction between factors shaping evolution and dynamics of a pathogen. The modeling-style, commonly referred to as «biology-driven» or «bottom-up» approach, is designed to answer the questions «Why», «How», and «How much», rather than merely describing data. PI worked on evolution and immunology of HIV, influenza virus, polio virus, vesicular stomatitis virus, and LCMV, and Plasmodium. The work was conducted in collaboration with virology and immunology laboratories in the USA (John Coffin at Tufts University, Boston, Leor Weinberger at the Gladstone Institute of Virology and Immunology, San Francisco, Raul Andino at UCSF, San Francisco, Rafi Ahmed at Georgia State University, Atlanta).

In 1999-2001, Igor published several papers, which detailed the basic mechanism of the rapid evolution of HIV in untreated patients and argued that it is due to the compensatory mutations of early CTL escape mutants, which prediction has been confirmed later. At the same time, he determined the relative role of stochastic effects and natural selection in HIV evolution. Later, he developed the first accurate theory of asexual evolution taking into account strong linkage effects existing between many evolving sites. Later, he showed that even rare recombination, which is the case for HIV, can accelerate evolution. His team then estimated the most important average parameters of HIV evolution, such as the average selection coefficient, the effective populations size, and the recombination rate.

Recently, Igor has proposed a model of primary HIV infection explaining the early formation of the latent HIV reservoir and proposing an evolutionary role for latency. He also investigated the stability and evolution of a virus in the presence of Defective Interference Particles and helped Leor Weinberger (Gladstone Institute) and Raul Andino (UCSF) to get NIH and DARPA grants on this topic . For all these tasks, Igor developed his own, custom-made mathematical approaches. In 2018, PI’s team published a paper explaining data on the evolution of influenza in the host population driven by immune response. They also developed a high-fidelity method of measuring the fitness landscape from viral sequence data, which is the most essential parameter for predicting viral adaptation.

Diplomas

1985 — M.S., Theor. Semicond. Physics, Electrical Engineering Institute, St. Petersburg, Russia

1988 — Ph.D., Theor. Semic. Physics, Ioffe Physico-Technical Institute, St. Petersburg, Russia

Academic appointments

2017-2021 — Group Leader, Sorbonne Université (Pierre et Marie Curie), Laboratory of Computational and Quantitative Biology, Paris

2015-2017 — Specialist, Microbiology, University of California, San Francisco

2012-2015 — Staff Scientist, The Gladstone Institute of Virology and Immunology, San Francisco

2007-2011 — Research Associate Professor, Department of Molecular Biology and Microbiology, Tufts University, Boston

2001-2007 — Research Assistant Professor, Department of Molecular Biology and Microbiology, Tufts University, Boston

1996-2000 — Research Associate, Department of Molecular Biology and Microbiology, Tufts University, Boston

1993-1995 — Postdoctoral (Research) Associate, Department of Physics, University of California, Los Angeles

1990-1993 — Postdoctoral (Research) Associate, Theoretical Physics Institute, University of Minnesota, Minneapolis

1985-1990 — Researcher, Theoretical Department, A.F. Ioffe Physical Technical Institute, St. Petersburg, Russia

Languages

  • English: fluent
  • Russian: native
  • French: advanced
  • German: intermediate
  • Italian: elementary

Visiting positions

May 2016 — Pekin University, Center for Quantitative Biology, Bejing, China.

Oct-Nov 2015 — UPMC, Laboratory of Computational and Quantitative Biology, UMR 7238
CNRS- UPM, Paris, France

Oct-Dec 2011 — University of Cologne, Department of Physics, Germany

Aug-Sep 2011 — The Gladstone Institute of Virology and Immunology, San Francisco

June-July, 2011 — University of California at San Diego, Department of Chemistry and Biochemistry, La Jolla, CA, USA

Feb 2011 — Workshop on Microbial Evolution, KITP, University of California at Barbara, CA, USA

Mar, Jun-Aug 1995 — Harvard University, Department of Physics, Boston, USA

Apr-May, 1995 — Leiden University, Department of Physics, Leiden, Netherlands

Research areas

  • Computational and theoretical biology
  • Dynamics and evolution of viruses
  • Semiconductor Physics

Associations and service

2021-2022 — Organization Committee «QLife WS Quantitative Viral Dynamics Across Scales, March 21-25, 2022»

2021-now  — Topic Editorial Board of Microorganisms

2018-2019 — Guest Editor of Pathogens

2006-2009 — Associate Editor of the Journal of Mathematical Analysis and Applications

2015-2017 — Member of the Society for Mathematical Biology

2013-2016 — Member of the American Mathematical Society

1990-1995 — Member of the American Physical Society

Teaching

2017-2019 — Instructor in Evolution Modeling for third-year students of Sorbonne-Polytech, Paris

2013  — Adjunct Professor in Astronomy for business majors, University of San Francisco

1995  — Lecturer in Electricity and Magnetism for CS and EE majors, University of California at Los Angeles

2018-2020 — Public lectures at la Fête de la Science, Sorbonne Université Campus Pierre et Marie Curie, Paris, https://www.sorbonne-universite.fr/les-lois-de-la-selection-naturelle

Reviewer for international journals

AIDS Research Retroviruses

American Naturalist

BMC Evolution

BMC Microbiology

Bulletin of Mathematical Biology

Cell

Critical Reviews of Microbiology

EMBO

Genetics

Genes

Evolutionary Applications

Frontiers of Immunology

Inter. Journal of Molecular Sciences

Journal of Statistical Mechanics

Journal of Virology

Lancet Microbe

Nucleic Acid Research

Pathogens

Proceed. of Nat. Acad. Sciences of USA

PLoS Computational Biology

PLoS Pathogens

PLoS Genetics

PLoS ONE

Physical Review Letters

Physical Review B

Theoretical Population Biology

Viruses

Reviewer for grants

2020:Vici grant proposal, Hague, Netherlands
2011:NIH research grant proposal (R01)
2012:NIH research grant proposal (R01)
2012:Vienna Research Group grant proposal for Young Investigators

Grants received

2017-2021:

ANR grant «Hosting high-level researchers», $600,000 direct expenses
Title: «The fusion of modeling and data analysis to study the evolution of pathogens»
Host organization: UPMC, Paris
Role: Principal Investigator

2016-2020:

Grant DARPA-BAA-16-35—INTERCEPT, USA, $273 000
Role: Co-PI (with Raul Andino, University of California San Francisco)

2014-2016:

grant R21AI109611 from National Institutes of Health, $500,000 total
Title: «Experiment & theory to test an evolutionary fitness role for lentiviral latency»
Role: Co-Principal Investigator (with Leor Weinberger, Gladstone Institutes)

2006-2010:

grant R01AI063926 from National Institutes of Health, USA, $1000,000 total
Title: «Working models of HIV persistence and evolution»
Role: Principal Investigator

2001-2005:

grant K25AI01811 from National Institutes of Health, USA, $600,000 total
Title: «Search for working models of HIV persistence and evolution»
Role: Principal Investigator

Invited talks at seminars and conferences
(28 total)

2021:Seminar «Progression to AIDS and HIV controllers», IAME, University de Paris, INSERM
2021:Seminar «Progression to AIDS and HIV controllers», University of Heidelberg, Germany
2020:Seminar «Progression to AIDS and HIV controllers», University of Montpelier, France
2019:Nordita workshop «From Molecular Basis to Predictability and Control of Evolution», Stockholm, Sweden.
2018:3d IFOM Symposium «Evolution, Resistance, and Cancer», IFOM, Milan, Italy.
2015:5th Interdisciplinary Symposium «Genomics and Microbial Communities», Institut de Biologie Paris-Seine, UPMC, Paris
2015:Two seminars on the evolutionary role of HIV latency: Groupe de Travail math / bio, UPMC, Paris; Biophysique, Institut Curie, Paris
2015:Seminar on the evolutionary role of HIV latency, IBM, Almaden Research Center, San Jose, CA
2014:Seminar on modeling HIV evolution caused by the host immune response, IBM, Almaden, CA
2014:Program «Evolution of Drug Resistance», Kavli Institute of Theoretical Physics, University of California at Santa Barbara, CA
2014:«Workshop on From Within-Host Dynamics to the Epidemiology of Infectious Disease», Institute of Mathematical Biosciences, Columbus, Ohio
2014:Seminar on therapeutic inteference particles, Institute of Biology, Paris Seine, UPMC, 2012: Workshop on Discrete and Topological Models in Molecular Biology and AMS special session on Discrete Models in Molecular Biology, University of Florida, Tampa, FL, USA
2011:Seminar on modeling immune response against influenza, Department of Physics, University of Exeter, Exeter, UK
2011:Workshop on Microbial Evolution, Kavli Institute for Theoretical Physics, University of California at Santa Barbara, Santa Barbara, CA, USA
2010:Seminar on evolution theory, The National Evolutionary Synthesis Center, Duke University, Durham, NC, USA
2009:International 3rd Eastern European and Central Asia AIDS Conference, Moscow, Russia
2007:Workshop on Theoretical Immunology, University of Leuven, Belgium
2006:Workshop on Mathematical Population Genetics, Edinburgh, UK
2006:Seminar on evolution theory, Department of Evolution and Ecology, University of California at Davis, CA, USA
2006:Two seminars on evolution theory and modeling HIV immunology, Department of Physics, University of California at San Diego, CA, USA
2005:Seminar on modeling HIV immunology, Centre for Non-Linear Dynamics, Department of Physiology, McGill University, Montreal, Canada
2004:Seminar on asexual evolution, Department of Biostatistics, University of California at Los Angeles, CA, USA
2004:Seminar on evolution and dynamics of HIV at A.F. Ioffe Physical Technical Institute, St. Petersburg, Russia
2003:Seminar in Genomics Center, Harvard University, Cambridge, MA, USA
2002:Seminar on evolution theory of asexual populations, Department of Applied Mathematics, Massachusetts Technological Institute, Cambridge, MA, USA
2002:Seminar on evolution theory of asexual populations, Department of Physics, Harvard University, Cambridge, MA, USA
1998:Meeting on HIV Dynamics and Evolution, organized by University of California at San Diego
1995:Seminar on antigenic escape of HIV from the immune response, Department of Microbiology, University of California, CA, USA

Other presentations at conferences

2021:EEID Agropolis International (Université de Montpelier)
2021:WIP ANRS AC41 (ANRS, Paris)
2021:Alphy: Genomique evolutive (Université de Montpelier, Lyon, Grenoble)
2020:Approche Interdisciplinaire de l’Evolution Moleculaire, Annual Meeting (CNRS INEE )
2012-2013:4 informal seminars and 6 talks at the University of California at San Francisco
1996-2012:20+ conferences including annual series:
Meeting on HIV evolution and dynamics (organized by UCSD, La Jolla, CA, USA)
Retroviruses (Cold Spring Harbor, NY)
Conference on Retroviruses and Opportunistic Infections
Keystone meetings at Keystone, Colorado, and Banff, Alberta, Canada
1990-1995:8-9 conferences including annual series:
Meeting of American Physical Society
Aspen Workshop on Condensed Matter Theory, Aspen, Colorado

Instruction of graduate and postdoctoral students

        2020:        Luis Pereira, postdoctoral associate, Sorbonne Université Campus Pierre et Marie Curie, Paris
2018:Ayuna Barlukova, postdoctoral associate, Sorbonne Université Campus Pierre et Marie Curie, Paris
2017-2019:Gabriele Pedruzzi, postdoctoral associate, Sorbonne Université Campus Pierre et Marie Curie, Paris
2014-2015:Ariel Weinberger, collaborator and postdoctoral fellow at Harvard University
2013-2015:Luke Rast, intern, Gladstone Institute of Virology and Immunology, University of California, San Francisco
2012:Lisa Bishop, postdoctoral associate, Gladstone Institute of Virology and Immunology, University of California at San Francisco
2008-2012:Rebecca Batorsky, graduate student, Department of Physics at Tufts University, Boston.
2006-2009:Rinat Sergeev, postdoctoral associate, Department of Molecular Biology and Microbiology, Tufts University. (Current employment: Institute for Quantitative Social Science, Harvard University)
2007-2008:Elena Gubankova, postdoctoral associate, Department of Molecular Biology and Microbiology, Tufts University
2003-2005:Speranta Gheorghiu, postdoctoral associate, Department of Molecular Biology and Microbiology, Tufts University

Collaboration with experimental teams

Raul Andino lab, Department of Microbiology and Immunology, University of California at San Francisco

Weinberger lab of Synthetic and Quantitative Virology, Gladstone Institute of Virology and Immunology, San Francisco

Coffin lab of Retrovirology, Department of Molecular Biology and Microbiology, Tufts University, Boston

John Coffin, Director (now Special Consultant), the HIV Drug Resistance Program at National Cancer Institute, NIH, Frederick, DC, USA

Novella lab of RNA virus evolution, College of Medicine, University of Toledo, Toledo, OH, USA

Rafi Ahmed, Director, Emory Vaccine Center, Atlanta, GA, USA

BIBLIOGRAPHY

Results beyond the state-of-art

Rouzine* IM, Wakeley J, Coffin JM (2003) The solitary wave of asexual evolution. Proc Nat Acad Sci 100: 587-592
The first accurate mathematical analysis predicting the evolution rate of a population with a large number of linked loci in the absence of recombination.

Rouzine IM, Weinberger, AD, and Weinberger*, LS (2015) An evolutionary role for HIV latency in enhancing viral transmission. Cell 160, 1002–12
An evolutionary role for HIV latency is a Trojan horse effect during transmission.

Rouzine* IM, Coffin JM (2001) Transition between stochastic evolution and deterministic evolution in the presence of selection: general theory and application to virology [review]. Microbio Mol Bio Rev 65: 151-185
The classical stochastic theory of evolution 1930-1970 is reviewed and adapted for virology.

IM Rouzine (2020) An evolutionary model of progression to AIDS. Microorganisms 8, 1714
The first closed model of progression to AIDS is proposed based on gradual adaptation of HIV to a host is proposed.

Good BH, Rouzine IM, Balick DJ, Hallatschek O, and Desai* MM (2012) Distribution of fixed beneficial mutations and the rate of adaptation in asexual populations. Proc Natl Acad Sci U S A 109: 4950-4955
The traveling wave theory is generalized for the arbitrary distribution of mutational fitness effects.

Rouzine* IM and Rozhnova G (2018) Antigenic evolution of viruses in host populations. PLoS Pathogens 14, e1007291
A model of genetic evolution of a virus in a host population accumulating the immune memory connects epidemiology to immunology and the modern evolution theory. The predicted parameters are tested against data for influenza A.

Batorsky R, Kearney MF, Palmer SE, Maldarelli F, Rouzine* IM, Coffin JM (2011) Estimate of effective recombination rate and average selection coefficient for HIV in chronic infection. Proc Natl Acad Sci U S A 108: 5661

Rouzine* IM, Coffin JM (1999) Linkage disequilibrium test implies a large effective population number for HIV in vivo. Proc Nat Acad Sci 96: 10758-10763
The effective population size and the effective recombination rate of HIV are estimated correctly for the first time.

Rouzine* IM, Coffin JM (2005) Evolution of HIV under selection and weak recombination. Genetics 170: 7-18

Rouzine* IM, and Coffin, JM (2010) Many-site adaptation in the presence of infrequent recombination. Theor Pop Bio 77: 189-204
Recombination is incorporated in the modern multi-locus evolution theory

Rouzine* IM, Coffin JM (1999) Search for the mechanism of evolution in the pro gene of HIV in vivo. J Virol 73: 8167-8178.
The high diversity of HIV within and between infected individuals is explained as a result of compensatory mutations for the early escape mutations in CD8 T cell epitopes. The average value of the effective selection coefficient for HIV patient is estimated.

Rouzine* IM, McKenzie FE (2003) Link between immune response and parasite synchronization in malaria. Proc Nat Acad Sci 100: 3473-3478
Chaotic oscillations of parasitemia in malaria are predicted as a result of communication between different parasites in different phases of cell replication.

Books

Rouzine IM. (2020) «Mathematical Models of Evolution. Volume 1: One-locus and multi-locus theory and recombination», in series Mathematics and life sciences, De Gruyter, Berlin/Boston.

Book chapters

* Auteur correspondant

Rouzine* IM, Coffin JM (1999) Interplay between experiment and theory in development of a working model for HIV-1 population dynamics, in: Origin and Evolution of Viruses, eds. E.Domingo, R.Webster and J.Holland, Academic, London, 1999, pp.225-262.

Raikh* ME, Ruzin IM (1991) Transmittance fluctuations in randomly non-uniform barriers and incoherent mesoscopics, review, in: Mesoscopic Phenomena in Solids, eds. B.L.Altshuler, P.A.Lee and R.A.Webb. North Holland, Amsterdam, 1991, pp. 301-354.

Raikh* ME, Ruzin IM (1990) Distribution function of conductance of finite-size inhomogeneous barrier structures, in: Hopping and Related Phenomena, eds. H. Fritzsche and M. Pollak. World Scientific, Singapore, 1990, pp. 217-241.

https://www.worldscientific.com/doi/abs/10.1142/9789814434447_0017

Peer-reviewed publications (64 total)

Computational and theoretical biology

Pedruzzi G, Rouzine* IM (2021) An evolution-based high-fidelity method of epistasis measurement: theory and application to influenza. PLoS. Pathog. 17, e1009669. IF 6.2

Barlukova A, Rouzine* IM (2021) The evolutionary origin of the universal distribution of mutation fitness effect. PLoS Comp. Bio. 17, e1008822. IF 4.5

Rouzine IM (2020) An evolutionary model of progression to AIDS. Microorganisms 8, 1714   IF 4.2

Pedruzzi G, Rouzine IM * (2019) Epistasis detectably alters correlations between genomic sites in a narrow parameter window. PLoS ONE 14, e0214036.  IF 2.7

Pedruzzi G, Barlukova A, Rouzine* IM (2018) Evolutionary footprint of epistasis. PLoS Computational Biology 14, e1006426. IF 4.5

Rouzine* IM, Rozhnova G (2018) Antigenic evolution of viruses in host populations. PLoS Pathogens 14, e1007291. IF 6.5

Lidsky PV, Andino R *, Rouzine IM (2017) Variability in viral pathogenesis: modeling the dynamic of acute and persistent infections. Current Opinion in Virology 23, 120-124.   IF 5.6

Xiao Y, Rouzine IM, Bianco S, Acevedo A, Goldstein  EF, Farkov, M, Andino M *. RNA recombination enhances adaptability and is required for virus spread and virulence (2016). Cell host & microbe 19 (4), 493-503.   IF 17.9

LI Rast, IM Rouzine, G Rozhnova, L Bishop, AD, Weinberger*, LS. Conflicting selection pressures will constrain viral escape from interfering particles: principles for designing resistance-proof antivirals (2016). PLoS Computational Biology 12 (5), e1004799.   IF 4.0

Rouzine, IM, Weinberger, AD, and Weinberger*, LS (2015) An evolutionary role for HIV latency in enhancing viral transmission. Cell 160, 1002–1012.  IF 31.4

Razooky, BS, Pai, A, Aull, K, Rouzine, IM, and Weinberger*, LS (2015) A hardwired HIV latency program. Cell 160, 990–1001.   IF 31.4

Batorsky, R, Sergeev, RA, Rouzine*, IM (2014) The route of HIV escape from immune response targeting multiple sites is determined by the cost-benefit tradeoff of escape mutations. PLoS Comp. Bio. 10, e1003878.  IF 4.0

Rouzine IM, Razooky, BS, Weinberger*, LS (2014) Stochastic variability in HIV affects viral eradication. Proc Natl. Acad. Sci. U S A 111, 13251–13252.   IF 9.5

Rouzine* IM, Coffin JM, Weinberger LS (2014) 15 years later: Hard and soft selection sweeps confirm a large population number for HIV in vivo. PLOS Genetics 10, e1004179.   IF 5.5

Rouzine IM, Weinberger* LS (2013) Reply to »Coadaptive stability of interfering particles with HIV-1 when there is an evolutionary conflict». J Virol 87: 9960.    IF 4.4

Rouzine IM, Weinberger* LS (2013) Design requirements for interfering particles to maintain co-adaptive stability with HIV-1. J Virol 87: 2081-2093.   IF 4.4

Rouzine* IM, Weinberger LS (2013) The quantitative theory of within-host viral evolution [review]. J Stat Mech (2013) P01009   

Good BH, Rouzine IM, Balick DJ, Hallatschek O, and Desai* MM (2012) Distribution of fixed beneficial mutations and the rate of adaptation in asexual populations. Proc Natl Acad Sci U S A 109: 4950-4955   IF 9.5                    

Batorsky R, Kearney MF, Palmer SE, Maldarelli F, Rouzine* IM, Coffin JM (2011) Estimate of effective recombination rate and average selection coefficient for HIV in chronic infection. Proc Natl Acad Sci U S A 108: 5661-    IF 9.5

Rouzine*, IM, and Coffin, JM (2010) Many-site adaptation in the presence of infrequent recombination. Theor Pop Bio  77: 189-204    

Sergeev, RA, Batorsky, RE, and Rouzine*, IM (2010) Model with two types of CTL regulation and experiments on CTL dynamics. J Theor Bio 263: 369-84.    

Sergeev, RA, Batorsky, RE, and Rouzine*, IM (2010) Interpreting the effect of vaccination on steady state infection in animals challenged with simian immunodeficiency virus. J Theor Bio 263: 385-92.     

Brunet*, E, Rouzine, IM, and Wilke, CO (2008) The stochastic edge in adaptive evolution. Genetics 179: 603-620    IF 3.8

Dutta, RN, Rouzine, IM, Smith, SD, Wilke, CO, and Novella*, IS (2008) Rapid adaptive amplification of preexisting variation in an RNA virus. J Virol 82: 4354-4362.    IF 4.4

Rouzine*, IM, Brunet, E, and Wilke, CO (2008) The traveling-wave approach to asexual evolution: Muller’s ratchet and speed of adaptation. Theor Popul Biol 73: 24-46.     

Rouzine* IM, Coffin JM (2007) Highly fit ancestors of partly sexual populations. Theor Pop Bio 71: 239-150.   

Gheorghiu-Svirschevski S, Rouzine* IM, Coffin JM (2007) Increasing sequence correlations limits the efficiency of recombination in a multi-site evolution model. Mol Bio Evol 254: 574-586.    IF 10.2

Rouzine* IM, Sergeev RA, Glushtsov AI (2006) Two types of cytotoxic lymphocyte regulation explain kinetics of immune response to human immunodeficiency virus. Proc Nat Acad Sci 103: 666-671   IF 9.5

Rouzine* IM, Coffin JM (2005) Evolution of HIV under selection and weak recombination. Genetics 170: 7-18   IF 3.8

Rouzine* IM, Murali-Krishna K, Ahmed R (2005) Generals die in friendly fire, or modeling immune response to HIV. J Comp Appl Math 184: 258-274.  IF 1.4

Rouzine* IM, Wakeley J, Coffin JM (2003) The solitary wave of asexual evolution. Proc Nat Acad Sci 96: 587-592   IF 9.5

Rouzine* IM, McKenzie FE (2003) Link between immune response and parasite synchronization in malaria. Proc Nat Acad Sci 100: 3473-3478    IF 9.5

Rouzine* IM, Coffin JM (2001) Transition between stochastic evolution and deterministic evolution in the presence of selection: general theory and application to virology [review]. Microbio Mol Bio Rev 65: 151-185    IF 13.4

Rouzine* IM, Coffin JM (1999) Linkage disequilibrium test implies a large effective population number for HIV in vivo. Proc Nat Acad Sci 96: 10758-10763   IF 9.5

Rouzine* IM, Coffin JM (1999) Search for the mechanism of evolution in the pro gene of HIV in vivo. J Virol 73: 8167-8178   IF 4.4

Rouzine* IM, Coffin JM (1999) T cell turnover in SIV infection [comment]. Science 284: 555b IF 37.2

Theoretical physics

(Note spelling of name «Rouzine» as «Ruzin” from Cyrillic original name «Рузин»)

Cooper* NR, Halperin BI, Hu C, Ruzin IM Statistical properties of the low-temperature conductance peak heights for Corbino disks in the quantum Hall regime. Phys Rev B 1997; 55: 4551- 

Cooper* NR, Halperin BI, Ruzin IM Thermoelectric response of an interacting two-dimensional electron gas in quantizing magnetic field. Phys Rev B 1997; 55: 2344-

Ruzin* IM, Cooper N, Halperin BI Non-universal behavior of finite quantum Hall systems as a result of weak macroscopic inhomogeneities. Phys Rev B 1996; 53: 1558-

Ruzin* I, Feng S Universal relation between longitudinal and transverse conductivities in quantum Hall effect. Phys Rev Lett 1995; 74: 154-

Dykhne AM, Ruzin* IM Theory of the fractional quantum Hall effect: The two-phase model. Phys Rev B 1994; 50: 2369-2379

Aleiner IL, Ruzin* IM Density of states of localized phonons in a pinned Wigner crystal. Phys Rev Lett 1994; 72: 1056-1060

Ruzin IM Hall transport in non-uniform two-dimensional conductors. Phys Rev B 1993; 47: 15727-15734

Ruzin* IM, Marianer S, Shklovskii BI Pinning of a two-dimensional Wigner crystal by charged impurities. Phys Rev B 1992: 46: 3999-4008  

Ruzin IM, Chandrasekhar V, Levin EI, Glazman* LI Stochastic Coulomb blockade in a double-dot system. Phys Rev B 1992; 45: 13469-13478  

Glazman LI, Ruzin IM, Shklovskii* BI Quantum transport and pinning of one-dimensional Wigner crystal. Phys Rev B 1992; 45: 8454-8463

Glazman* LI, Ruzin IM Metal-to-insulator crossover in mesoscopic wires [review]. Physica Scripta 1992; T42: 122-

 Ruzin IM Fine structure of hopping conductance fluctuations in finite-size semiconductors. Phys Rev B 1991; 43: 11864-11872 

SD Baranovskii, EI Levin, IM Ruzin, H Fritzsche, BI Shklovskii Computer simulation of energy relaxation and recombination of nonequilibriumelectrons in a disordered system with localized electronic states International Journal of Modern Physics C 1991; 2 : 220-222

Raikh ME, Ruzin* IM Size effect in the longitudinal hopping conduction of a narrow two-dimensional channel. Phys Rev B 1990; 42: 11203-11207

Ruzin IM,  Shklovskii BI Theory of hopping conductivity due to long-wavelength excitation. Sov Phys Semicond 1989; 23: 1164-1167

Orlov AO, Raikh ME, Ruzin IM, Savchenko AK Statistical properties of mesoscopic conductivity fluctuations in a short-channel GaAs field-effect transistor. Sov Phys JETP 1989; 69: 1229-1236

Baranovskii SD, Fritzsche H, Levin EI, Ruzin IM, Shklovskii BI Theory of low-temperature photoconductivity and photoluminescence in amorphous semiconductors. Sov Phys JETP 1989; 69: 773-782

Raikh ME, Ruzin IM Fluctuations of the hopping conductance of one-dimensional systems. Sov Phys JETP  1989; 68: 642-647

Orlov AO, Raikh ME, Ruzin IM, Savchenko AK Distribution function of hopping conductance fluctuations of a short GaAs field- effect transistor channel. Solid State Communic 1989; 72: 169-172

Raikh ME, Ruzin IM, Shklovskii BI Influence of localized states in a barrier on a fluctuation tunnel current flowing across a metal-semiconductor contact. Sov Phys Semicond 1988; 22: 1254-1257

Raikh ME, Ruzin IM Mesoscopic behavior of the transverse hopping conductivity of an amorphous film. Sov Phys Semicond 1988; 22: 799-805

Levin EI, Ruzin IM, Shklovskii BI Transverse hopping conductivity of amorphous films in strong electric fields. Sov Phys Semicond 1988; 22: 401-408

Raikh ME, Ruzin IM Transparency fluctuations in randomly inhomogeneous barriers of finite area. Sov Phys JETP 1987; 65: 1273-1282

Tartakovskii AV, Fistul MV, Raikh ME, Ruzin IM Hopping conductivity of metal-semiconductor-metal contacts. Sov Phys Semicond 1987; 21: 370-373

Raikh ME, Ruzin IM Temperature dependence of fluctuation excess currents flowing across a metal-semiconductor contact. Sov Phys Semicond 1987; 21: 283-285

Raikh ME, Ruzin IM Mesoscopic behavior of the temperature dependence of the transverse hopping conductivity of an amorphous film. JETP Lett 1986; 43: 563-565

Gerbstein* YuM, Ruzin IM, Chudnovskii FA Fractal dimensionality of silver dendrites in the two-dimensional ionically conducting system Ag-AgI-Ag. Sov Phys Solid State 1986; 28: 1073-1074

Raikh* ME, Ruzin IM Fluctuation mechanism of excess tunnel currents in reverse-biased p-n— junctions. Sov Phys Semicond 1985; 19: 745-750