Eric O. Freed, Ph.D.
- Center for Cancer Research
- National Cancer Institute
- Building 535, Room 110
- Frederick, MD 21702-1201
- 301-846-6223 (office)
- 301-846-6483 (lab)
- efreed@mail.nih.gov
RESEARCH SUMMARY
Dr. Freed is recognized as a leader in the field of virus assembly who has made important strides in understanding the mechanisms of retroviral replication at the molecular level, with an emphasis on late stages of the HIV-1 replication cycle. As Director of the HIV DRP, he oversees a program of basic, translational, and clinical research aimed at developing a better understanding of HIV that can be used to generate more-effective treatment strategies. His research focuses on HIV-1 Gag trafficking, Env incorporation, virus assembly, budding, release, maturation, and drug resistance. Dr. Freed has a special interest in the complex relationship between viral proteins and cellular factors and pathways, believing that characterizing fundamental aspects of the retrovirus replication cycle will suggest novel targets for the development of antiretroviral therapies. Recent work in the Freed lab has also focused on the ability of Env mutations to broadly rescue defects in virus replication, including those conferred by antiretrovirals.
Areas of Expertise
Eric O. Freed, Ph.D.
Research
Assembly and Release of HIV-1 and Other Retroviruses
Retroviral Gag proteins are synthesized in the cytoplasm of the infected cell and assemble into virus particles that typically bud from the plasma membrane (PM). Expression of Gag proteins alone is generally sufficient for the assembly and release of noninfectious, virus-like particles (VLPs). The mature Gag proteins [matrix (MA), capsid (CA), and nucleocapsid (NC)] are generated concomitant with virus release upon cleavage of the Gag precursor by the viral protease (PR) [Freed, Nat. Rev. Microbiol. 2015]. PR-mediated Gag processing leads to virus maturation, a morphological transition essential for virus infectivity. Retroviral gag genes often encode other domains and spacer peptides in addition to MA, CA, and NC. For example, the HIV-1 Gag precursor includes two spacer peptides (SP1 and SP2) and the p6 domain.
Retroviral Gag trafficking and assembly. After Gag synthesis, the MA domain directs Pr55Gag to the PM. The affinity of the MA domain for membrane is provided in part by a myristic acid moiety covalently attached to the N-terminus of MA. Sequences in MA downstream of the myristate also contribute to membrane binding—in particular, a highly basic patch of amino acid residues.
A large body of data indicates that HIV-1 assembly takes place predominantly at the PM [Freed, Nat. Rev. Microbiol. 2015]. Although the cellular determinants that regulate the site of HIV-1 assembly remain to be fully defined, we demonstrated that lipid rafts serve as sites for assembly at the PM [Ono & Freed, PNAS 2001] and identified the phosphoinositide lipid phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2] as a host factor involved in directing Gag to the PM. Depleting PI(4,5)P2 leads to the retargeting of HIV-1 assembly to multivesicular bodies (MVBs) and severely disrupts virus particle production [Ono et al., PNAS 2004]. Structural studies have shown that HIV-1 MA, as well as the MA domain of several other retroviruses, interacts directly with PI(4,5)P2 and that some of the basic residues we identified as being important for Gag targeting to the PM engage in electrostatic interactions with PI(4,5)P2. We hypothesize that host factors in addition to PI(4,5)P2 play a vital role in the trafficking of Gag to the PM. For example, we have demonstrated that the ADP ribosylation factors (Arfs) and Golgi-localized, gamma-ear-containing, Arf-binding (GGA) proteins function in directing Gag to the PM and modulating virus budding [Joshi et al., Mol. Cell 2008]. We are currently working to define the role of host cell machinery in Gag trafficking to the PM and will seek to develop inhibitors of HIV-1 Gag trafficking, membrane binding, and assembly. In this project, we will also define viral and cellular determinants involved in directing HIV-1 assembly to the virological synapse, from which cell–cell transfer efficiently takes place. We have also been interested in the role of inositol-hexakisphosphate (IP6) in HIV-1 assembly [Mallery et al., Cell Rep. 2019; Mallery et al., Sci. Adv. 2021] and have discovered that the cellular protein PSGL-1, when incorporated into virus particles, blocks the ability of those particles to bind to target cells [Fu et al., PNAS 2020].
Env incorporation and function. The envelope (Env) glycoproteins of HIV-1 are synthesized as a polyprotein precursor, gp160, that is proteolytically processed by a cellular protease to generate the surface (SU) glycoprotein gp120 and the transmembrane (TM) glycoprotein gp41 [Checkley et al., J. Mol. Biol. 2011]. Incorporation of Env glycoproteins into virions is an essential step in the replication process; however, the mechanism by which the Env glycoproteins are incorporated remains incompletely characterized. Several lines of evidence suggest that HIV-1 Env glycoproteins are actively recruited into virions via direct interactions between Env and MA; for example, mutations in both the MA domain of Gag and the cytoplasmic tail of gp41 can block HIV-1 Env incorporation. We showed that in most cell lines and in primary cell types, gp41 truncations severely disrupt Env incorporation but that in some cell lines these gp41 truncation mutants are efficiently incorporated [Murakami & Freed, PNAS 2000]. The cell-type-dependent requirement for the gp41 cytoplasmic tail in Env incorporation hints at the involvement of host cell factors. However, the identity of such factors remains to be defined. We are currently using a range of cell biology, virology, biochemical, and imaging approaches to characterize viral and cellular determinants of Env incorporation. Our recent findings highlight a requirement for trimerization of the MA domain of Gag in Env incorporation [Tedbury et al., PNAS 2016; Tedbury et al., J. Virol. 2020). Our ongoing work has demonstrated that the cellular MARCH family of E3 ubiquitin ligases restricts the expression and incorporation of a range of viral glycoproteins including HIV-1 Env, VSV-G, Ebolavirus GP, and the spike protein of SARS-CoV-2 [Lun et al., mBio 2021].
More than two dozen drugs, most of which target the viral enzymes reverse transcriptase (RT), protease (PR), or integrase (IN), are currently available to treat HIV-1-infected individuals. These drugs, when used in combination (combination antiretroviral therapy or cART), effectively suppress virus replication in most patients. However, resistance to cART does arise in some individuals, particularly in the context of poor adherence, suboptimal drug regimens, or lack of viral load monitoring. Resistance is usually associated with mutations in the viral genes targeted by antiretrovirals (ARVs). However, in some cases, resistance arises without mutations in the drug-target gene. For example, many patients fail PR inhibitor (PI)-based therapy without acquiring mutations in PR, and in a number of individuals treated with the highly potent IN strand-transfer inhibitors (INSTIs) dolutegravir (DTG) and raltegravir (RTG), patients fail therapy without the virus acquiring mutations in IN. During propagation of HIV-1 mutants containing substitutions in the p6 domain of Gag that severely delay virus replication, we selected for mutations in Env that rescue virus replication. Each of these Env mutants replicated efficiently in T-cell lines at concentrations of DTG that blocked WT virus replication. Confirming the ability of Env mutations to provide resistance to DTG, we performed selections for DTG resistance and identified additional Env mutations that conferred resistance to DTG. Resistance was linked to the ability of the Env mutations to significantly enhance virus spread through cell-to-cell contact. These results demonstrate that, at least in vitro, mutations in Env can confer resistance to an ARV [Van Duyne et al., PNAS 2019]. Recent work has demonstrated that the Env mutations can confer resistance not only to the INSTI DTG but also to RT and PR inhibitors [Hikichi et al., mBio 2021]. Ultimately, we plan to fully define the mechanism by which the identified mutations in Env confer escape from ARVs and determine whether Env-mediated escape also occurs in vivo.
Retrovirus budding. The p6 domain of HIV-1 Gag is required for efficient virus budding. We mapped the virus release function of p6 to a highly conserved Pro-Thr-Ala-Pro (PTAP) motif near the N-terminus of p6 [Huang et al., J. Virol. 1995; Demirov et al., J. Virol. 2002; Fujii et al., Nat. Rev. Microbiol. 2007]. Other retroviral Gag proteins also possess "late domains" that, like the PTAP motif of p6, promote virus release.
Numerous lines of evidence support the hypothesis that retroviral late domains function by interacting with host factors—specifically, components of the cellular endosomal sorting complex required for transport (ESCRT) machinery [Freed, Nat. Rev. Microbiol. 2015]. The ESCRT machinery is composed of four multiprotein complexes (ESCRT-0, I, II, and III) and a variety of accessory proteins including Alix and the ATPase Vps4. This cellular apparatus functions in the sorting and release of cargo proteins into vesicles that bud into late endosomes and also plays a key role in the abscission step of cytokinesis. Retroviruses have evolved to usurp this cellular budding machinery to promote their release from the PM. Work from several labs, including ours, demonstrated that HIV-1 recruits the ESCRT machinery primarily through a direct interaction between the PTAP motif in p6 and the ESCRT-I component tumor susceptibility gene 101 (Tsg101). Secondary interactions occur between p6 and Alix.
Virion maturation. PR-mediated cleavage of the Gag and Gag–Pol precursors leads to a dramatic change in virion morphology, a process known as maturation. The highly ordered nature of Gag processing and the strict dependence on complete processing for proper virion maturation make the Gag processing cascade a potential target for drug development. Indeed, the betulinic acid derivative dimethylsuccinyl betulinic acid [PA-457 or bevirimat (BVM)] potently inhibits HIV-1 infectivity by targeting a late Gag processing event: the cleavage of the CA–SP1 processing intermediate to mature CA [Li et al., PNAS 2003]. By specifically disrupting this step in Gag processing, BVM treatment leads to the formation of poorly infectious viral particles with aberrantly condensed cores. We have selected and characterized a number of single amino acid mutations in the CA–SP1 boundary region that confer resistance to BVM, establishing this region of Gag as the target of the inhibitor [Adamson et al., J. Virol. 2006]. Clinical trials conducted with BVM provided mixed results; in some patients significant reductions in viral loads were achieved, whereas in other patients no benefit of BVM therapy was observed. We and others were able to attribute this lack of response to polymorphisms in SP1. We also performed studies on a second HIV-1 maturation inhibitor, PF-46396, developed by Pfizer. While structurally distinct from BVM, PF-46396 also inhibits CA–SP1 processing. Particularly interesting is our observation that a number of PF-46396-resistant mutants are severely defective for assembly and infectivity in the absence of the compound but produce infectious virions in its presence [Waki et al., PLoS Pathog. 2012]. We are also engaged in studies aimed at elucidating the structure of the maturation inhibitor-binding site in assembled Gag. We believe that increased structural information on the HIV-1 maturation inhibitor-binding site will lead to the discovery of new, structurally distinct inhibitors. Finally, with collaborators at DFH Pharma, we have identified a series of highly potent BVM derivatives that display broad activity against strains of HIV-1 that are resistant to BVM [Urano et al., Antimicrob. Agents Chemother. 2016; Urano et al., J. Virol. 2019]. This work advances our efforts to develop virus maturation inhibitors as an antiviral strategy.
Publications
Mutations in the HIV-1 envelope glycoprotein can broadly rescue blocks at multiple steps in the virus replication cycle
Biochemical evidence of a role for matrix trimerization in HIV-1 envelope glycoprotein incorporation
Structural and functional insights into the HIV-1 maturation inhibitor binding pocket
Phosphatidylinositol (4,5) bisphosphate regulates HIV-1 Gag targeting to the plasma membrane
Overexpression of the N-terminal domain of TSG101 inhibits HIV-1 budding by blocking late domain function
Biography
Eric O. Freed, Ph.D.
Dr. Eric Freed received his Ph.D. in 1990 in the laboratories of Drs. Rex Risser and Howard Temin at the University of Wisconsin-Madison and did postdoctoral work with Dr. Temin at UW-Madison in 1991. His work in Madison focused on the function of the murine leukemia virus and HIV envelope glycoproteins in membrane fusion and virus entry. He joined the Laboratory of Molecular Microbiology at the National Institute of Allergy and Infectious Diseases (LMM/NIAID) in 1992, where he worked with Dr. Malcolm Martin on HIV assembly and entry/post-entry events in the HIV replication cycle. In 1997 Dr. Freed was appointed as a Tenure-Track Investigator in LMM/NIAID, and he was promoted to a tenured Senior Investigator position in 2002. In 2003 he joined the HIV Drug Resistance Program (HIV DRP, renamed the HIV Dynamics and Replication Program in 2015) as Head of the Virus-Cell Interaction Section and was appointed to the NCI Senior Biomedical Research Service in 2011. Dr. Freed was appointed Deputy Director of the HIV DRP in 2014 and Director of the Program in 2015. He was an Organizer of the 2004 Cold Spring Harbor Meeting on Retroviruses, 2006 ASCB Conference "Cell Biology of HIV-1 and Other Retroviruses," 2012 Keystone Symposium "Frontiers in HIV Pathogenesis, Therapy and Eradication," 2014 Keystone Symposium "The Ins and Outs of Viral Infection: Entry, Assembly, Exit and Spread," Viruses 2016 Conference "At the Forefront of Virus–Host Interactions," Viruses 2018 Conference "Breakthroughs in Virus Replication," 2018 gp41 Cytoplasmic Tail Structure and Function Workshop, and Viruses 2020 “Novel Concepts in Virology.” He also served on the Scientific Committee of the International Retroviral Nucleocapsid Protein and Assembly Symposium in 2013, 2016, and 2019 and the Organizing Committee of the Annual Meeting of the American Society for Virology in 2018. He has served as Co-Organizer of the Annual HIV DRP Conference and Annual David Derse Memorial Lecture and Award since 2012 and Organizer of the Annual George Khoury Memorial Lecture since 2014. Dr. Freed is the founding Editor-in-Chief of Viruses and was appointed Editor of Journal of Molecular Biology in 2012 and Editor of Recent Advances in HIV-1 Assembly and Release in 2013. He also currently serves on the Editorial Boards of a number of journals, including Journal of Virology, Retrovirology, and Frontiers in Virology, and is an Associate Editor for Science Advances and Fields Virology. He was a sitting member of the NIH AIDS Discovery and Development of Therapeutics (ADDT) study section (2012-2017) and served as ADDT Chair from 2015 to 2017. He is currently Chair of the CCR Center for Molecular Microscopy Advisory Panel and CCR Cryo-EM Expert Users Committee, Co-Chair of the NIH Virology Interest Group, and Scientific Advisory Board Member of the NIH Center for HIV-1 RNA Studies. He is also Co-Director of the University of Maryland Virology Program and an Adjunct Professor in the Department of Cell Biology and Molecular Genetics at the University of Maryland, College Park. Dr. Freed received the NCI Mentor of Merit Award in 2010 and the NCI Women Scientists Advisors Mentoring and Leadership Award in 2021 for excellence in mentoring and guiding the careers of scientists in all stages of their careers. He received the Outstanding Science Alumni Award from Penn State University in 2014 and the NCI Research Highlights Award in 2016. In recognition of his outstanding contributions to the field of retrovirology, Dr. Freed was awarded the KT Jeang Retrovirology Prize in 2018 and the Ohio State University Center for Retrovirus Research Distinguished Research Career Award in 2020. He was elected to Fellowship in the American Academy of Microbiology in 2019 and was appointed to the Pittsburgh Center for HIV Protein Interactions in 2020.
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Team
News
Confirmed Talent Award from French Government
Geraldine Vilmen received an award from the French Government in December 2021 as a "confirmed talent" representing France overseas. She is part of an esteemed group of young people highlighting opportunities worldwide.
D.Phil. in Systems Approaches to Biomedical Science Awarded by University of Oxford
Hana Valer was awarded a D.Phil. degree in Biological and Biomedical Sciences by the University of Oxford in November 2021 after successfully defending her dissertation on the interaction between influenza A virus RNA-dependent RNA polymerase and cellular GTPase Rab11a. Her project was a collaboration between the Dunn School of Pathology and Division of Structural Biology (STRUBI) at the University of Oxford and the Diamond Light Source, the UK's national synchrotron science facility.
NIH Fellows Awards for Research Excellence
James Kirui and Yuta Hikichi won 2022 NIH Fellows Awards for Research Excellence (FARE) for travel to attend and present their 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/presentation of the abstracts. Members of the Freed Lab who were FARE awardees in previous years include Rachel Van Duyne (2015), Lillian Kuo (2012), Kayoko Waki (2012), Angelica Martins (2012), Muthukumar Balasubramaniam (2010), Benjamin Luttge (2010), Catherine Adamson (2009), and Karine Gousset (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.
Yuta Hikichi received an IARF award in 2021 to support his research project on "Mechanism of HIV-1 Env-Mediated Drug Resistance In Vitro and In Vivo" and Alex Kleinpeter received IARF awards in 2020 and 2021 to support his research project on "Elucidating the Role of IP6 in HIV-1 Assembly and Maturation."
The following postdoctoral fellows in the Freed Lab received IARF awards in previous years:
Cheng man (Bonnie) Lun: "Antagonism of HIV-1 Replication by Cellular Factor MARCH E3 Ubiquitin Ligases and Viral Escape Pathways" (2019, 2020)
Melissa Fernandez: "Mechanism of HIV-1 Env Trafficking to the Virological Synapse” (2018, 2019)
Mariia Novikova: "Characterization of Antiretroviral Activity of Second-Generation Maturation Inhibitors and Mechanisms of Resistance" (2017)
Rachel Van Duyne: "Challenging the Paradigm for Antiretroviral Resistance through the Study of Non-Canonical HIV-1 Escape Mutants" (2017)
Emiko Urano: "Development of Potent and Broadly Active HIV-1 Maturation Inhibitors" (2016)
Mariia Novikova: "Mechanisms of HIV-1 Gag Lattice Formation and Env Incorporation" (2016)
Rachel Van Duyne: "Characterizing the Host Cell Factors Involved in HIV-1 Gag Trafficking to Sites of Virus Assembly" (2015)
Robert Buckheit: "The Effect of Host Antiviral Restriction Factors on Viral Budding and Maturation" (2014)
Lillian Kuo: "Characterizing the Role of HIV-1 p6-Alix Binding in HIV-1 Cell-to-Cell Infectivity" (2011, 2012)
Philip Tedbury: "HIV-1 Gag in Assembly and Release: Interactions with gp41 and Cellular Host Factors" (2011, 2012)
Eric Freed Received 2020 NCI Women Scientists Advisors Mentoring and Leadership Award
In recognition of his commitment to mentoring and his role in promoting diversity, Eric Freed received the 2020 NCI Women Scientists Advisors Mentoring and Leadership Award, which honors "exceptional dedication, leadership, and tireless efforts to promote and nurture NCI women scientists at all stages of their careers."
Eric Freed Received 2020 Distinguished Research Career Award from The Ohio State University Center for Retrovirus Research
Eric Freed was selected by the Center for Retrovirus Research of The Ohio State University to receive the 2020 Distinguished Research Career Award. This annual award honors the distinguished research career of a scientist working in the field of retrovirology. The retrovirologist is nominated by student and faculty members of the Center for Retrovirus Research and as part of the award recognition is invited to give a special lecture to all members of the Ohio State University biomedical research community. To read more about this award, click here.
NCI Director's Innovation Award
James Kirui received a 2020 NCI Director’s Innovation Award for his research proposal "Using highly sensitive reporter virus vectors to study late stages of HIV-1." With support from this award, Dr. Kirui developed innovative bioluminescent reporter virus vectors that provide a simple, rapid tool for functional studies of HIV-1 replication as well as high-throughput screening for cellular factors and small molecules that promote or inhibit HIV-1 particle production.
Travel Award, 39th Annual Meeting of the American Society for Virology (ASV 2020)
Melissa Fernandez was awarded an American Society for Virology Postdoctoral Scholar Travel Award for her abstract submission to ASV 2020 (meeting canceled due to COVID-19 pandemic).
Dr. Eddie Méndez Award
Melissa Fernandez was selected to be a recipient of the 2nd Annual Dr. Eddie Méndez Award, which recognizes outstanding postdoctoral scientists who are conducting research in cancer biology or infectious diseases. As an awardee, Dr. Fernandez presented her latest research findings at a scientific symposium in 2020 honoring Dr. Eddie Méndez and had the opportunity to discuss her work with faculty members of the Fred Hutchinson Cancer Research Center.
Postdoctoral Fellowship, Japan Society for the Promotion of Science
The Japan Society for the Promotion of Science (JSPS) awarded a 2020-2021 Research Fellowship to Yuta Hikichi for his project "Mutations in the HIV-1 envelope glycoprotein contribute to HIV drug resistance." The fellowship program sponsored by this society supports meritorious biomedical research projects undertaken in NIH laboratories by Japanese postdoctoral researchers. Emiko Urano was awarded a JSPS Research Fellowship from 2013 to 2015.
Pathway to Independence Award (K99/R00)
Melissa Fernandez successfully competed for a K99/R00 Pathway to Independence (PI) Award from the National Institutes of Health in 2019. The PI Award Program establishes and maintains a strong cohort of new and talented, NIH-supported, independent investigators. This program is designed to facilitate a timely transition of outstanding postdoctoral researchers or clinician-scientists from mentored research positions to independent, tenure-track or equivalent faculty positions, and to provide independent NIH research support during the transition that will help these individuals launch competitive, independent research careers.
Poster Awards, Spring Research Festival
Ahlam Majadly was awarded "Outstanding Poster—Infectious Pathogens and Epidemiology" for her presentation at the 2019 Spring Research Festival, which is sponsored by the National Cancer Institute at Frederick and the other eight agencies of the National Interagency Confederation for Biological Research. Ahlam's presentation highlighted the research she conducted as a student trainee in the Freed Lab over the past year. Other members of the Freed Lab who won poster awards at the Spring Research Festival in previous years include Maya Swiderski (2016), Megan Mounts (2014), Scott MacDonald (2013), Darren D'Souza (2012), and Nishani Kuruppu (2011). All six of these award recipients were undergraduate students or Werner H. Kirsten student interns under the mentorship of Abdul Waheed.
Fellowship in the American Academy of Microbiology
Eric Freed was elected to Fellowship in the American Academy of Microbiology (AAM) in 2019. AAM Fellows are recognized as distinguished scientists who are "elected through a highly selective, annual, peer review process, based on their records of scientific achievement and original contributions that have advanced microbiology....Each elected Fellow has built an exemplary career in basic and applied research, teaching, clinical and public health, industry or government service."
New Investigator Scholarships, Conference on Retroviruses and Opportunistic Infections
Mariia Novikova, Phuong Pham, and Rachel Van Duyne were awarded New Investigator Scholarships to present their research findings at the 2019 Conference on Retroviruses and Opportunistic Infections (CROI). CROI scholarship awardees in previous years include Rachel Van Duyne (2018, 2017), Phuong Pham (2018), Mariia Novikova (2017, 2016), Justin Kaplan (2017), Emiko Urano (2016, 2014), Lillian Kuo (2013), and Catherine Adamson (2007).
2018 KT Jeang Retrovirology Prize
Eric Freed was awarded the 2018 KT Jeang Retrovirology Prize. This annual award recognizes mid-career investigators who have made outstanding contributions to the field of retrovirology.
NIH Postbac Poster Day Awards
Phuong Pham received an Outstanding Poster Award at the NIH Postbac Poster Day in 2018. Her presentation on "Progress in Developing Broadly Active and Highly Potent HIV-1 Maturation Inhibitors" was recognized as one of the best among the 772 posters presented by the NIH postbacs this year. Members of the Freed Lab who received Outstanding Poster Awards at the NIH Postbac Poster Day in previous years include Nishani Kuruppu and Justin Kaplan (2016).
Travel Awards, HIV DRP Think Tank Meeting
Rachel Van Duyne received a $1000 travel award from the HIV DRP for one of the two best presentations by NCI fellows at the 2018 and 2017 HIV DRP Think Tank Meetings. Members of the Freed Lab who received travel awards in previous years include Mariia Novikova (2016), Emiko Urano (2015), Kayoko Waki (2011), and Muthukumar Balasubramaniam (2010).
Travel Awards, Fall HIV/AIDS & Cancer Virology Think Tank Meeting
Mariia Novikova won a $1000 travel award for her outstanding talk at the 2017 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. Members of the Freed Lab who received travel awards in previous years include Mariia Novikova and Rachel Van Duyne (2016), Philip Tedbury (2014), Angelica Martins (2013), and Emiko Urano (2013).
Research Highlights Award at 2016 NCI Scientific Retreat
In 2016, Eric Freed received a Research Highlights Award for his presentation on "Development of Potent and Broadly Active HIV-1 Maturation Inhibitors" at the NCI Annual Intramural Scientific Retreat.
Sallie Rosen Kaplan Postdoctoral Fellowship for Women Scientists
Melissa Fernandez (2nd from right) was selected for the Sallie Rosen Kaplan (SRK) Postdoctoral Fellowship for Women Scientists at the National Cancer Institute in 2015. The SRK Fellowship is a highly competitive annual program that provides additional mentoring opportunities, networking, seminars, and workshops to help prepare NCI’s female postdoctoral fellows for the competitive nature of the job market and help them to transition to independent research careers. The highlight of this selective program is a 30-week course entitled "Career Building for Women in Science," which includes two day-long workshops. The SRK Fellowship also includes mentoring opportunities with successful women scientists from government, industry, and academia.
Rachel Van Duyne and Mariia Novikova (2nd and 4th from left) were selected for SRK Fellowships in 2014.
2014 Outstanding Science Alumni Award, Penn State University
Eric Freed was selected by the Eberly College of Science to receive the 2014 Outstanding Science Alumni Award at Penn State University. This award recognizes alumni who have a record of significant professional achievements in their field and are outstanding role models for the current students in the college.
Award for Outstanding Scientific Presentation, 9th International Retroviral Nucleocapsid Protein and Assembly Symposium
Philip Tedbury received an award for one of the best posters at the 2013 International Retroviral Nucleocapsid Protein and Assembly Symposium in Montreal, Canada. His presentation on "Identification of a matrix mutation that globally rescues Env incorporation defects: implications for matrix structure and Env recruitment" highlighted the latest findings from his research project supported by an Intramural AIDS Research Fellowship.
Special Recognition as a Top Peer Reviewer for the Journal of Virology
In 2011, Eric Freed merited special recognition as one of the 25 top peer reviewers (among 1570 reviewers) for the Journal of Virology. This recognition was based on his outstanding attention to a high number of manuscripts during the year, providing insightful reviews within an exceptionally short time frame.
2010 NCI Mentor of Merit Award
Eric Freed was selected as an NCI Mentor of Merit in 2010 for excellence in mentoring and guiding the careers of trainees in cancer research. Dr. Freed was nominated by present and past trainees who view his mentorship as outstanding. NCI Director Harold Varmus presented the Mentor of Merit citation to him at the NCI Director's Awards ceremony in November 2010.
2010 Multi-Investigator Award Sponsored by Center for Cancer Research (CCR) and Office of AIDS Research (OAR)
In 2010, Eric Freed and Vineet KewalRamani of the HIV DRP, NCI-Frederick, and Sriram Subramaniam of the Laboratory of Cell Biology, NCI-Bethesda, successfully competed for a $150,000 CCR/OAR-sponsored multi-investigator award with their research proposal "Catching HIV in the act: Structural studies of HIV transport from antigen-presenting cells into the T-cell nucleus." In total, four CCR/OAR-sponsored awards were made to 11 investigators within and between the Frederick and Bethesda campuses of the National Cancer Institute.
Young Investigator Award, 2008 International Feline Retrovirus Research Symposium
Benjamin Luttge was awarded the Young Investigator Award for his oral presentation at the 2008 International Feline Retrovirus Research Symposium in Vienna, Austria.
Travel Award, 2008 NCI-Frederick Spring Research Festival Symposium
Benjamin Luttge won a travel award for the best oral presentation at the 2008 NCI-Frederick Spring Research Festival Symposium on "Virology: from Genetic Vehicles to Human Pathogens."
2006 Travel Fellowship, HIV & Cancer Virology Faculty, Center for Cancer Research
In 2006, Catherine Adamson won one of the three available travel fellowships awarded by the HIV & Cancer Virology Faculty, Center for Cancer Research, National Cancer Institute.
Alumni
Lab Life
Freed Lab — August 2019
Left to right: Melissa Fernandez, Sherimay Ablan, James Kirui, Cheng man (Bonnie) Lun, Alex Kleinpeter, Jennifer Simmons, Eric Freed, Lwar Naing, Ahlam Majadly, Abdul Waheed, Nicole Powell, Yuta Hikichi
Freed Lab — May 2018
Left to right: Hannah Carter, Sherimay Ablan, Rachel Van Duyne, Melissa Fernandez, Mariia Novikova, Cheng man (Bonnie) Lun, Ali Khan, Abdul Waheed, James Kirui, Phuong Pham, Eric Freed
Current Lab Members
Sherimay Ablan, B.A., Research Biologist
Sherimay earned her B.A. in biology from the University of Hawaii at Manoa. She contributes to all the research projects in the lab, with a primary focus on developing potent and broadly active HIV-1 maturation inhibitors (MIs) and elucidating the molecular, biochemical, and structural basis for MI activity. Sherimay received the Federal Technology Transfer Award for her work on MIs and the NIH Special Act or Service Award for her role in the design, planning, and renovation of a BSL2* HIV containment laboratory.
Eva Agostino, B.S., Postbaccalaureate Fellow (CRTA)
Eva earned her B.S. in biological sciences from the University of Maryland at College Park. During her undergraduate career, she did research on pathogenic O157:H7 E. coli outbreaks in Dr. Julie Kase’s lab at the FDA and SARS-CoV-2 entry in Dr. Meg Scull’s lab at the University of Maryland. She is currently working on elucidating the inhibitory mechanism of a neutral sphinomyelinase-2 inhibitor on HIV-1 replication and the interaction between the gp41 cytoplasmic tail and matrix lattice during envelope glycoprotein incorporation.
Yuta Hikichi, Ph.D., Postdoctoral Fellow (Visiting)
Yuta earned his Ph.D. in medical sciences from The University of Tokyo and AIDS Research Center, National Institute of Infectious Diseases, Japan, under the mentorship of Dr. Tetsuro Matano. His work is primarily focused on understanding the mechanism by which mutations in the HIV-1 envelope glycoprotein confer broad resistance to antiretrovirals. Yuta was awarded a Japan Society for the Promotion of Science Research Fellowship in 2020 and 2021, NIH Intramural AIDS Research Fellowship in 2021, and NIH Fellows Award for Research Excellence (FARE) in 2022.
James Kirui, Ph.D., Research Fellow
James earned his Ph.D. in cellular and molecular biology from the University of Wisconsin at Madison under the mentorship of Dr. Andrew Mehle. He is investigating host factors involved in HIV-1 Gag trafficking, assembly, and release. James received the NCI Director’s Innovation Award in 2020 for developing highly sensitive reporter-virus vectors that provide a simple, rapid tool for functional studies of the late stages in HIV-1 replication as well as high-throughput screening for cellular factors and small molecules that promote or inhibit HIV-1 particle production. He also received a 2022 Fellows Award for Research Excellence (FARE) from NIH. In December 2021, he was promoted to Research Fellow.
Alex B. Kleinpeter, Ph.D., Postdoctoral Fellow (CRTA)
Alex earned his Ph.D. in biochemistry and structural biology from the University of Alabama at Birmingham in Dr. Chad Petit’s lab. He is characterizing the role of the small-molecule metabolite inositol hexakisphosphate (IP6), a critical host cofactor in HIV-1 replication, in facilitating the formation of the immature HIV-1 Gag lattice and mature capsids. Alex was awarded Intramural AIDS Research Fellowships from NIH in 2021 and 2020 to support his research.
Meghna Tripathi, B.S., Postbaccalaureate Fellow (CRTA)
Meghna earned her B.S. in molecular and cellular biology from the University of Arizona, where she conducted phylogenetic analysis of HIV-1 vpr sequences in Dr. Nafees Ahmad’s lab. She is currently working on characterizing the antiviral mechanism of capsid inhibitor 1261 in the HIV-1 replication cycle, which may prove to be a promising potential compound for therapeutics and clinical trials.
Hana Veler, Ph.D., Postdoctoral Fellow (Visiting)
Hana was awarded a D.Phil. degree in biomedical sciences – pathology by the University of Oxford in November 2021 after successfully defending her dissertation on the interaction between influenza A virus RNA-dependent RNA polymerase and cellular GTPase Rab11a under Prof. Ervin Fodor’s mentorship. Hana’s project was a collaboration between the Dunn School of Pathology and Division of Structural Biology (STRUBI) at the University of Oxford and the Diamond Light Source, the UK's national synchrotron science facility. In the Freed lab, she is currently investigating how HIV-1 Gag cleavage/structural rearrangement of the matrix lattice during virion maturation affects envelope glycoprotein activation.
Geraldine Vilmen, Ph.D., Postdoctoral Fellow (Visiting)
Geraldine earned her Ph.D. in virology from the University of Paris Saclay under the mentorship of Dr. Audrey Esclatine. Her postdoctoral training in Dr. Amit Sharma’s lab at Ohio State University included work on SARS-CoV-2 replication and SHIV/macaque models of HIV-1 infection. She is currently investigating the role of host restriction factors in viral replication, focusing on the processing of viral glycoproteins such as SARS-CoV-2 spike or HIV-1 Env, key players in host cell receptor binding and membrane fusion during virus entry. In 2021 she received a Confirmed Talent Award from the French Government for representing France overseas as part of an esteemed group of young people highlighting opportunities worldwide.
Abdul A. Waheed, Ph.D., Associate Scientist
Waheed received his Ph.D. in membrane biochemistry from the University of the Ryukyus, Okinawa, Japan. His current research is focused on host factors involved in HIV-1 replication and small-molecule inhibitors of HIV-1 replication. He was promoted to Staff Scientist in 2016 and Associate Scientist in 2019. In addition to mentoring all the student interns in the Freed lab, he has served in leadership roles in the CCR Staff Scientist/Staff Clinician Organization. Read more about Waheed in his CCR investigator profile.