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Vinay K. Pathak, Ph.D.

Vinay K. Pathak, Ph.D.

  • Center for Cancer Research
  • National Cancer Institute

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.
picture of Sushila Kumari
Postdoctoral Fellow (Visiting)
Sushila Kumari, Ph.D.
picture of Chenglei Li
Postdoctoral Fellow (Visiting)
Chenglei Li, Ph.D.
Picture of Mohammad Munshi
Postdoctoral Fellow (Visiting)
Mohamed Husen Munshi, Ph.D.
picture of Rokeya Siddiqui
Postdoctoral Fellow (Visiting)
Rokeya Siddiqui, Ph.D.
A photo of Ellie Bare standing outside
Postbaccalaureate Fellow
Ellie Bare, B.S.

News

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 2022 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 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).

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.

Rokeya Siddiqui received an IARF award in 2022 and 2021 to support her research project on "Identification of Host Dependency Factors that Influence Nuclear Import of HIV-1 Capsid." 

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

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)

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,”

Image
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.]

Travel Award, CCR and DCEG Staff Scientist and Staff Clinician Retreat

Krista Delviks-Frankenberry received a $1,500 travel award for the best oral presentation at the 14th Annual CCR and DCEG Staff Scientist and Staff Clinician Retreat in April 2018.

Norman P. Salzman Memorial Poster Award in Virology

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Belete Desimmie receiving 2016 Norman P. Salzman Memorial Poster Award in Virology

Belete Desimmie won a 2016 Norman P. Salzman Memorial Poster Award in Virology for his work on APOBEC3 inhibition of HIV-1 replication.  This annual NIH-wide award is given to three postdoctoral fellows per year to recognize outstanding research in the field of virology under the mentorship of an NIH, CBER, or Leidos scientist.  Postdoctoral fellows from all NIH campuses, including Bethesda and Frederick, can apply for the award.  Dr. Desimmie presented his poster at the 18th Annual Norman P. Salzman Virology Symposium in November 2016 and received a cash award for his achievement.

Poster Awards, Spring Research Festival at NCI-Frederick

Taisuke Izumi won a poster award for his presentation at the 2013 NCI-Frederick Spring Research Festival.  Members of the Pathak lab who won poster awards at the Spring Research Festival in previous years include Tobias Paprotka (2011), Krista Delviks-Frankenberry (2007), Rebecca Russell (2007), Patricia Henry (2006), Galina Nikolenko (2006), and Hongzhan Xu (2006).

2013 Awards from Frederick County Science & Engineering Fair

In 2013, Catoctin High School senior Maria Hamscher presented the research she has been conducting in the Pathak lab at the 32nd Annual Frederick County Science & Engineering Fair in Frederick, Maryland.  Maria won the 2nd Place Award in Cellular & Molecular Biology, High School Division and also a Distinguishing Achievement 2nd Place Award, given by the Commissioned Officers Association of the U.S. Public Health Service, for her research entitled "Testing the P2A Cleavage System for Gene Therapy Vectors."  Since July 2012, she has been working as a Werner H. Kirsten Student Intern in the Pathak lab under the mentorship of Krista Delviks-Frankenberry.

NIH Asian and Pacific Islander American Organization Award

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Vinay Pathak receiving 2012 NIH Asian and Pacific Islander American Organization (APAO) Award

Vinay Pathak was the recipient of the 2012 NIH Asian and Pacific Islander American Organization (APAO) Award for outstanding accomplishments in biomedical research.  Each year, the APAO honors two outstanding individuals in the NIH Asian and Pacific American community: one for Scientific Achievement, recognizing scientists who have made significant accomplishments in biomedical research; and the second for Leadership Excellence, recognizing non-scientists who exemplify leadership excellence by example, mentorship, and empowerment of Asian and Pacific Americans to promote diversity and support the overall mission of NIH.  Dr. Pathak received his Scientific Achievement award at the NIH APAO annual awards ceremony in December 2012.

Award from U.S.-Russia Joint Working Group on Biomedical Research Cooperation

In 2012, Vinay Pathak was the recipient of one of the five grants that the U.S.-Russia Joint Working Group on Biomedical Research Cooperation awarded to National Cancer Institute intramural investigators for their highly meritorious research applications.  Dr. Pathak is the Principal Investigator on a project focused on characterizing broadly neutralizing antibodies by phage display peptide libraries.

Norman P. Salzman Memorial Award in Virology

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Tobias Paprotka, recipient of 2011 Norman P. Salzman Memorial Award in Virology

Tobias Paprotka won the 2011 Norman P. Salzman Memorial Award in Virology for his work on XMRV.  This annual NIH-wide award is given to only one postdoctoral fellow per year to recognize outstanding research in the field of virology under the mentorship of an NIH, Center for Biologics Evaluation and Research, or SAIC scientist.  Postdoctoral fellows from all NIH campuses, including Bethesda and Frederick, can apply for the award.  Dr. Paprotka presented his research at the Thirteenth Annual Norman P. Salzman Memorial Symposium in Virology on November 10, 2011 and received a plaque and a cash award for his achievement.  As Dr. Paprotka's mentor, Vinay Pathak also received a plaque at the Symposium.

Postdoctoral Fellowship, Japan Society for the Promotion of Science

Taisuke Izumi was awarded a Postdoctoral Fellowship from 2011 to 2013 by the Japan Society for the Promotion of Science. The fellowship program sponsored by this society supports meritorious biomedical research projects undertaken in NIH laboratories by Japanese postdoctoral researchers. Fellowships are awarded after a competitive review of research proposals.

Scholarship Award, Keystone Symposia on HIV Pathogenesis

Rebecca Russell was awarded a travel scholarship to present her research findings at the 2008 Keystone Symposia on HIV Pathogenesis.

2006 Travel Fellowship, HIV & Cancer Virology Faculty, Center for Cancer Research

In 2006, Jean L. Mbisa won one of the three available travel fellowships awarded by the HIV & Cancer Virology Faculty, Center for Cancer Research, National Cancer Institute.

Alumni

Daniel Ackerman, B.S.
2014-2015
Postbaccalaureate 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
Jean Lutamyo Mbisa, Ph.D.
2002-2008
Postdoctoral Fellow
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
Masoudeh Masoud Bahnamiri, Ph.D.
2022-2023
Postdoctoral 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.