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Vinay K. Pathak, Ph.D.

Vinay K. Pathak, Ph.D.

  • Center for Cancer Research
  • National Cancer Institute
Head, Viral Mutation Section

RESEARCH SUMMARY

Dr. Pathak has significantly advanced the field of lentiviral molecular virology with his studies of HIV-1 replication in infected cells.  Under his direction, the Viral Mutation Section has developed innovative live-cell microscopy methods to show that, in contrast to most HIV-1 replication models, intact viral cores are transported into the nucleus, complete reverse transcription in the nucleus, and disassemble (uncoat) near their integration sites just before integration.  Dr. Pathak’s group has significantly contributed to our understanding of how HIV-1 replicates in the presence of potent host restriction APOBEC3 proteins and antiviral drugs.  Additionally, Dr. Pathak’s group played a key role in discovering the origin of a newly identified retrovirus, XMRV, and in quelling a potential public health crisis by refuting the controversial claims associating this virus with chronic fatigue syndrome and prostate cancer.

Areas of Expertise

HIV Replication
Host Restriction Factors
Nuclear Import
Development of Novel Therapeutics

Publications

Selected Key Publications

HIV-1 cores retain their integrity until minutes before uncoating in the nucleus

Li C, Burdick RC, Nagashima K, Hu WS, Pathak V
Proc Natl Acad Sci U S A. 118: e2019467118, 2021.
Full-Text Article
[ Journal Article ]

HIV-1 uncoats in the nucleus near sites of integration (article awarded 2020 Cozzarelli Prize)

Burdick RC, Li C, Munshi M, Rawson JMO, Nagashima K, Hu W-S, Pathak VK
Proc Natl Acad Sci U S A. 117: 5486-5493, 2020. [ Journal Article ]

Dynamics and regulation of nuclear import and nuclear movements of HIV-1 complexes

Burdick RC, Delviks-Frankenberry KA, Chen J, Janaka SK, Sastri J, Hu W-S, Pathak VK
PLoS Pathog. 13(8): e1006570, 2017. [ Journal Article ]

Minimal contribution of APOBEC3-induced G-to-A hypermutation to HIV-1 recombination and genetic variation

Delviks-Frankenberry KA, Nikolaitchik OA, Burdick RC, Gorelick RJ, Keele BF, Hu W-S, Pathak VK
PLoS Pathog. 12(5): e1005646, 2016. [ Journal Article ]

Recombinant origin of the retrovirus XMRV

Paprotka T, Delviks-Frankenberry KA, Cingoz O, Martinez A, Kung H-J, Tepper CG, Hu W-H, Fivash MJ Jr, Coffin JM, Pathak VK
Science. 333: 97-101, 2011. [ Journal Article ]

Job Vacancies

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Team

picture of Ryan Burdick
Research Biologist
Ryan Burdick, M.S.
A photo of Sushila Kumari 2024
Postdoctoral Fellow (Visiting)
Sushila Kumari, Ph.D.
picture of Rokeya Siddiqui
Postdoctoral Fellow (Visiting)
Rokeya Siddiqui, Ph.D.
Photo of Akshay
Postdoctoral Fellow (Visiting)
Akshay Deshpande, Ph.D.
A photo of Ellie Bare standing outside
Postbaccalaureate Fellow
Ellie Bare, B.S.

News

Poster Presentations at the NIH HIV Structural Biology Meeting 2024

Ryan Burdick (biologist) and Chenglei Li (post-doc) presented posters at the 2024 HIV Structural Biology Meeting at NIH-Bethesda. A VideoCast is available here.

Krista Delviks-Frankenberry publishes in Nature Structural Molecular Biology

In collaboration with Yale University, Krista Delviks-Frankenberry publishes in the journal Nature Structural Molecular Biology, with her paper titled "Structural insights into PPP2R5A degradation by HIV-1 Vif" (2024).

Pathak lab at CSHL Retrovirology Meeting 2024

Members of the Pathak lab attended the 2024 Cold Spring Harbor Laboratory Retrovirology Meeting.

Ryan C. Burdick (biologist) delivered his talk as the recipient of the 2024 Uta Von Schwedler Award. Poster presentations were made by Ellie Bare (post-doc) and Chenglei Li (post-doc).

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Members of the HIV DRP Pathak lab at CSHL 2024

Photo of Pathak lab (with others) at CSHL.

Intramural AIDS Research Fellowships

Intramural AIDS Research Fellowship (IARF) awards from the Office of AIDS Research, Office of Intramural Research, and Office of Intramural Research & Training in the National Institutes of Health include full stipend support to successful candidates who demonstrate outstanding scientific potential through both an imaginative and thoughtful research plan and a well thought out career development plan.

Sushila Kumari received an IARF award in 2024 to support her research project.

The following postdoctoral fellows in the Pathak lab received IARF awards in previous years:

Rokeya Siddiqui received an IARF award in 2022 and 2021 to support her research.

Belete Desimmie:  "Identification of Novel Class of HIV Replication Inhibitors Targeting the HIV-1 Vif-A3G Interactions" (2014)

Narasimhan Jayanth Venkatachari:  "Identification of Small Molecule Inhibitors of Vif-A3G and Vif-A3F Interactions as Novel Antiviral Agents for the Treatment of HIV-1 Infection" (2010, 2011)

Ryan Burdick receives the 2024 Uta von Schwedler Prize for Retrovirology

Congratulations to Ryan Burdick for winning the 2024 Uta von Schwedler Prize.

The award was given to Ryan Burdick for his numerous contributions to our understanding of HIV-1 uncoating.  Ryan’s most recent paper, “HIV-1 uncoating requires reverse transcription of long double-stranded DNA” is now published in Science Advances. 

The Uta von Schwedler Prize for Retrovirology was established in 2012 to annually award and honor the accomplishments of a distinguished scientist in retrovirology. Ryan will receive a $1250 cash prize and present a short talk and poster at this year’s Retroviruses meeting at Cold Spring Harbor Laboratories.

Vinay Pathak talks at The Palm Springs Symposium On HIV/AIDS 

Vinay Pathak was an invited speaker at The Palm Springs Symposium On HIV/AIDS 2024. The title of his talk was "HIV-1 Uncoating Requires Synthesis of Long Reverse Transcription Products".

Travel Awards, Fall HIV/AIDS & Cancer Virology Think Tank Meeting

Ryan Burdick won a $1200 travel award for his outstanding oral presentation at the 2023 Fall HIV/AIDS & Cancer Virology Think Tank Meeting.  In addition Rokeya Siddiqui won a $800 travel award for her outstanding poster presentation at the 2023 Fall HIV/AIDS & Cancer Virology Think Tank Meeting. This annual Think Tank meeting on the NIH-Bethesda campus provides a venue for students, postdoctoral fellows, and staff scientists to present emerging work and hypotheses in the field of cancer virology.  The Think Tank travel awards are provided by the Center of Excellence in HIV/AIDS & Cancer Virology, Center for Cancer Research, NCI.  Previous winner from the Pathak lab: Krista Frankenberry (2022).

NIH Fellows Awards for Research Excellence

Sushila Kumari received a 2024 NIH Fellows Award for Research Excellence (FARE) for travel to attend and present his work at a scientific meeting in the U.S.  This award, which acknowledges outstanding scientific research performed by intramural postdoctoral fellows, is sponsored by the NIH Fellows Committee, Scientific Directors, and Office of Intramural Training and Education and is funded by the Scientific Directors.  FARE awards are based on scientific merit, originality, experimental design, and overall quality and presentation of the abstracts.

Members of the Pathak lab who were FARE awardees in previous years include Sushila Kumari (2022),  Chenglei Li (2021), Mohamed Husen Munshi (2020), Sanath Kumar Janaka (2017), Tobias Paprotka (2012), Narasimhan Jayanth Venkatachari (2012), Wei Bu (2010), Jessica Smith (2010), Rebecca Russell (2009), Krista Delviks-Frankenberry (2008), Yeshitila Friew (2007), Patricia Henry (2007), and Galina Nikolenko (2007).

New Investigator Scholarships, Conference on Retroviruses and Opportunistic Infections

Chenglei Li was awarded a New Investigator Scholarship to present his research findings in the 2021 Conference on Retroviruses and Opportunistic Infections (CROI).  CROI scholarship awardees in previous years include Mohamed Husen Munshi and Chenglei Li (2020), Mohamed Husen Munshi (2019), Belete Desimmie (2017), and Taisuke Izumi (2013).

Vinay Pathak Discussed HIV-1 Uncoating Discovery on PNAS Science Sessions Podcast

In a June 2021 interview on Science Sessions, the podcast program of the Proceedings of the National Academy of Sciences USA (PNAS), Vinay Pathak explained the story behind the HIV-1 uncoating discovery by his lab in collaboration with Wei-Shau Hu's research team, a groundbreaking advance that was awarded the 2020 PNAS Cozzarelli Prize in Biomedical Sciences. To listen to the podcast, click here.

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​ Image PNAS Science Sessions image of podcast by Vinay Pathak 1 June 2021 [Click and drag to move] ​

Podcast Featured Vinay Pathak Discussing Live-Cell Imaging of HIV-1

Vinay Pathak was interviewed in a podcast by Consultant360 Specialty Network on the research presented in the "Navigating to the Nucleus" session at the Conference on Retroviruses and Opportunistic Infections 2021, including his presentation on "Live-Cell Imaging of HIV-1 Nuclear Import, Uncoating, and Proviruses."  To listen to the podcast, click here.

PNAS Video on Cozzarelli Prize Awarded to Pathak and Hu Labs

In a video produced by Proceedings of the National Academy of Sciences USA (PNAS) about the 2020 Cozzarelli Prize in Biomedical Sciences, Vinay Pathak discusses the HIV-1 uncoating discovery by his research team in collaboration with Wei-Shau Hu’s lab.  The video can be viewed on the PNAS Cozzarelli Prize page and on the PNAS YouTube channel (click here).

The publication that Dr. Pathak discusses in the video (“HIV-1 uncoats in the nucleus near sites of integration,” PNAS 117:5486-5493, 2020) was also featured on the website of the Center for Cancer Research, National Cancer Institute (“New study overturns conventional understanding of how HIV infection occurs”) and highlighted on the front cover of the Cold Spring Harbor 2020 Retroviruses Meeting abstract book.

PNAS Cozzarelli Prize Awarded to Pathak and Hu Labs

A recent study published by the research groups of Vinay Pathak and Wei-Shau Hu in Proceedings of the National Academy of Sciences USA (“HIV-1 uncoats in the nucleus near sites of integration,”

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Still image of HIV-1 infection video

PNAS 117: 5486-5493, 2020) was awarded the 2020 Cozzarelli Prize in the class of Biomedical Sciences.  The Cozzarelli Prize is awarded to just 6 papers chosen from nearly 4,000 published research articles, one in each of the 6 classes of the National Academy of Sciences.  They represent the top scientific research published in PNAS in 2020.  To read more about this award, click here.

Uncoating of an infectious HIV-1 complex is shown at left.  Click on the figure for a full caption and here to download the original video (Movie S1 in the paper).

This study was also featured on the website of the Center for Cancer Research, National Cancer Institute (“New study overturns conventional understanding of how HIV infection occurs”) and highlighted on the front cover of the Cold Spring Harbor 2020 Retroviruses Meeting abstract book.

Research by Pathak and Hu Labs Featured on Cover of 2020 Retroviruses Meeting Abstract Book

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Cover image of 2020 Cold Spring Harbor Laboratory Retroviruses Meeting abstract book

A recent study published by the research groups of Vinay Pathak and Wei-Shau Hu in Proceedings of the National Academy of Sciences USA (“HIV-1 uncoats in the nucleus near sites of integration,” PNAS 117:5486-5493, 2020) was featured on the front cover of the Cold Spring Harbor Laboratory 2020 Retroviruses Meeting abstract book.  Pathak lab member Ryan Burdick launched the meeting with his talk on the study and reported that HIV-1 uncoats in the nucleus near sites of integration.  Contrary to the prevailing theory for more than 40 years that retroviral uncoating occurs in the cytoplasm, the study team showed that HIV-1 cores are essentially intact as they enter the nucleus, where they complete reverse transcription before uncoating near their sites of integration into the host genome.  These unexpected results fundamentally alter the current understanding of HIV-1 replication, which could lead to the development of more effective strategies and drugs for the treatment of HIV infections.

In the cover image, the left panel shows an HIV-1 capsid localized in the nucleus and the right panel shows a site of transcription of the viral genome at the site where the capsid localized.  To read more about the study, see the original research article and the commentary "Entering and breaking for HIV?" in Nature Reviews Microbiology.

This study was also awarded the 2020 PNAS Cozzarelli Prize in Biomedical Sciences and featured on the website of the Center for Cancer Research, National Cancer Institute (“New study overturns conventional understanding of how HIV infection occurs”).

CCR News Feature about HIV-1 Infection Study by Pathak and Hu Labs

[Excerpted from a 26 February 2020 news feature by Center for Cancer Research (CCR), National Cancer Institute]

New Study Overturns Conventional Understanding of How HIV Infection Occurs

With unprecedented detail, researchers have observed where and when the protective casing around the human immunodeficiency virus (HIV-1) is shed inside a human cell, which is an observation that overturns the conventional understanding of how the virus infects cells and replicates.  The finding was published February 24, 2020, in the Proceedings of the National Academy of Sciences (PNAS) USA.

“Understanding how HIV-1 replication occurs can provide valuable insights into essential interactions between the virus and the host cell,” explains Vinay K. Pathak, Ph.D., Senior Investigator in the Retroviral Replication Laboratory, part of the HIV Dynamics and Replication Program.

Despite the importance of understanding how the virus infects human cells, many details about this process have remained unknown.  Until now, many scientists suspected that the protective casing around the virus, called the viral capsid, was shed before the virus enters the center of a human cell, called the nucleus.  Once inside the nucleus, the virus begins to replicate itself. 

Pathak’s lab used a new approach to brightly label the viral capsid with fluorescence in order to track it.  Previous efforts to label the viral capsid with fluorescent proteins resulted in dimly labeled or defective viruses, making it difficult to study the uncoating process.  

Unexpectedly, they found that the viral capsid remained essentially intact after entering the nuclei of cells.  They also identified a key protein called CPSF6 that helps facilitate the transport of the virus, including its capsid, through the pores of a nucleus. 

“We hope that the insights gained in our studies will help to identify critical molecular interactions between the virus and the host that will facilitate the development of new classes of potent anti-retroviral drugs,” says Pathak. 

However, he notes, this study raises many unanswered questions. It’s still a mystery, for example, on how the full virus (capsid included) at a diameter of roughly 61 nanometers can squeeze through the pore of a human nucleus, which is only about 39 nanometers wide.  More research is needed to understand how this happens and to identify the mechanisms that help trigger the virus’s uncoating process. 

Infected cell nucleus

Confocal image of an infected cell nucleus (purple) shows an HIV-1 capsid core (green spot, left panel) just before uncoating and a transcriptionally active provirus (bright purple spot, right panel) that appears several hours later near the site of uncoating.  Image credit: Ryan C. Burdick

[This study was also awarded the 2020 PNAS Cozzarelli Prize in Biomedical Sciences and highlighted on the front cover of the Cold Spring Harbor 2020 Retroviruses Meeting abstract book.]

Alumni

Daniel Ackerman, B.S.
2014-2015
Postbaccalaureate Fellow
Masoudeh Masoud Bahnamiri, Ph.D.
2022-2023
Postdoctoral Fellow
Michal Bonar, Ph.D.
2018
Postdoctoral Fellow
Timothy Borbet, Ph.D.
2010-2011
Predoctoral Fellow
Wei Bu, Ph.D.
2007-2010
Postdoctoral Fellow
Chawaree Chaipan, Ph.D.
2009-2012
Postdoctoral Fellow
Mollie Charon, M.D.
2002-2003
Predoctoral Fellow
John Chen, M.S.
2017-2019
Postbaccalaureate Fellow
Belete Desimmie, M.D., Ph.D.
2013-2020
Postdoctoral Fellow
Hibiki Doi
2013
Special Volunteer
Yeshitila Friew, Ph.D.
2004-2010
Postdoctoral Fellow
Colleen Furey, B.S.
2014
Summer Student
Ariel Hagedorn
2012
Summer Student
Maria Hamscher
2012-2013
Summer Student
Carey Hwang, M.D., Ph.D.
1999-2001
Predoctoral Fellow, M.D./Ph.D. Student
Taisuke Izumi, Ph.D.
2011-2014
Postdoctoral Fellow
Sanath Kumar Janaka, Ph.D
2013-2016
Postdoctoral Fellow
Abhay Jere, Ph.D.
2006-2008
Postdoctoral Fellow
Adam Ketchum
2016
Summer Student
Chenglei Li., Ph.D.
2017-2024
Research Fellow
Jean Lutamyo Mbisa, Ph.D.
2002-2008
Postdoctoral Fellow
Mohamed Husen Munshi, Ph.D.
2019-2024
Postdoctoral Fellow (Visiting)
Michael Nekorchuk, Ph.D.
2014-2017
Postdoctoral Fellow
Theodore Nikolaitchik
2014
Summer Student
Galina Nikolenko, Ph.D.
2006-2009
Research Fellow
Tobias Paprotka, Ph.D.
2009-2011
Postdoctoral Fellow
Dongfei Qi, Ph.D.
2012-2017
Postdoctoral Fellow
Sara Rasmussen, M.D., Ph.D.
1999-2000
Predoctoral Fellow, M.D./Ph.D. Student
Rebecca Russell, Ph.D.
2005-2008
Postdoctoral Fellow
Jaya Sastri, Ph.D.
2013-2016
Postdoctoral Fellow
Shrey Shah
2015
Summer Student
Shruti Shah
2019
Summer Student
Mayu Shigemi
2012
Special Volunteer
Jessica Smith, Ph.D.
2008-2013
Postdoctoral Fellow
Evguenia Svarovskaia, Ph.D.
2000-2004
Research Fellow
David Thomas, Ph.D.
2002-2005
Scientist
Narasimhan Venkatachari, Ph.D.
2009-2013
Research Fellow
Yegor Voronin, Ph.D.
1999-2003
Predoctoral Fellow
Hongzhan Xu, M.D., Ph.D.
2001-2006
Research Fellow
Avanish Yendluri
2017
Summer Student
Wen-Hui Zhang, Ph.D.
1999-2002
Predoctoral Fellow

Covers

Cover graphic of 2020 Cold Spring Harbor Laboratory Retroviruses Meeting

HIV-1 Uncoats in the Nucleus Near Sites of Integration

Published Date

A recent study published by the research groups of Vinay Pathak and Wei-Shau Hu in Proceedings of the National Academy of Sciences USA (“HIV-1 uncoats in the nucleus near sites of integration,” PNAS 117:5486-5493, 2020) was featured on the front cover of the Cold Spring Harbor Laboratory 2020 Retroviruses Meeting abstract book.  Pathak lab member Ryan Burdick launched the meeting with his talk on the study and reported that HIV-1 uncoats in the nucleus near sites of integration.  Contrary to the prevailing theory for more than 40 years that retroviral uncoating occurs in the cytoplasm, the study team showed that HIV-1 cores are essentially intact as they enter the nucleus, where they complete reverse transcription before uncoating near their sites of integration into the host genome.  These unexpected results fundamentally alter the current understanding of HIV-1 replication, which could lead to the development of more effective strategies and drugs for the treatment of HIV infections.

In the cover image, the left panel shows an HIV-1 capsid localized in the nucleus and the right panel shows a site of transcription of the viral genome at the site where the capsid localized. 

To read more about the study, see the original research article and the commentary "Entering and breaking for HIV?" in Nature Reviews Microbiology.

This study was also awarded the 2020 PNAS Cozzarelli Prize in Biomedical Sciences and featured on the website of the Center for Cancer Research, National Cancer Institute (“New study overturns conventional understanding of how HIV infection occurs”).

Citation

Burdick RC, Li C, Munshi MH, Rawson, Nagashima K, Hu W-S, Pathak VK.  Cold Spring Harbor Laboratory Retroviruses Meeting Abstract Book, May 2020.