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Natasha D Durham PhD

TitleInstructor
InstitutionUMass Chan Medical School
DepartmentMicrobiology
AddressUMass Chan Medical School
368 Plantation Street AS8-1005
Worcester MA 01605
Phone744-455-6584
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    Other Positions
    InstitutionT.H. Chan School of Medicine
    DepartmentMicrobiology


    Collapse Biography 
    Collapse education and training
    University of Toronto, Toronto, ON, CanadaBSHuman Biology
    Imperial College, London, , United KingdomMSMolecular Biology & Pathology
    Mount Sinai School of Medicine, New York, NY, United StatesPHDBiomedical Sciences
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    2023 - 2024Junior Faculty Development Program, UMass Chan Medical School

    Collapse Overview 
    Collapse Summary
    Focus: Viral entry, antibodies & vaccines, single molecule techniques
    Collapse overview

    I am a non-tenure track Instructor in the Department of Microbiology at UMass Chan Medical School.  My research focus is on RNA viruses which are a major threat to human health, including HIV-1, Ebola virus, Influenza virus and Dengue virus. 

    I am a virologist by training with additional expertise in immunology and biophysics, having worked with Dr. Benjamin Chen (my PhD mentor), Dr. Talia Swartz (post-doc mentor), Dr. James Munro (post-doc mentor) and Dr. Leslie Goo (as a Scientist I in the Goo Group at the Chan Zuckerberg Biohub San Francisco).  My skills and experience are ideally suited to the development and use of (i) advanced biophysical approaches to probe the mechanisms of viral entry, (ii) virus-based tools compatible with novel detection platforms, (iii) functional cell-based assays to validate cell-free observations and (iv) novel anti-viral therapeutics and vaccine antigens.  My long-term goal is to understand the molecular mechanisms of viral entry and antibody neutralization, to inform the development of novel vaccines and therapeutics.

    My independent research is focused on the replication cycle of viruses with Class II fusogens.  Initial studies are on viral entry.  I develop and apply biophysical methods like single molecule FRET to interrogate the single-molecule behavior of these viral proteins, and better understand their contributions to the bulk population functions that are routinely observed with more common virological assays.

    1) The dynamics of Class II viral fusogens and their interacting structural proteins.  Dengue virus (DENV) is responsible for the most human arbovirus infections world-wide, with approximately 4 billion people currently residing in endemic areas.  The conformational heterogeneity of DENV E is particularly complex, and includes the intrinsic dynamics or ‘viral breathing’ of E on individual virions within a viral population, as well as antigenic differences between the four DENV serotypes.  Existing studies on DENV E do not provide information on single-protein (i.e. non-averaged) time-resolved movements of E in a virus population.  Our current studies are defining the dynamics of DENV E before viral entry (pre-attachment), drawing on our extensive experience with the Class I Ebola virus envelope glycoprotein (Durham et al., 2020; Durham et al., 2025; Durham and Munro, manuscript in preparation).  Future studies will compare how these dynamics change during viral entry and viral egress.  We are also interested in how viral mutations can alter overall protein conformation, as is the case with other viral proteins like HIV-1 Env (Durham et al., 2012), and protein dynamics, as previously shown for Ebola GP (Durham et al., 2025).  We use single molecule FRET to define these conformations, and in vitro cell-based assays to determine/confirm their functional significance.

    2) Novel therapeutic and prophylactic interventions.  We are utilizing our approach to target several steps in the flavivirus replication cycle, developing a variety of interventions such as vaccine antigens, therapeutic antibodies, RNA-based therapeutics and small molecule inhibitors.  Our initial focus is on using patient-derived broadly neutralizing DENV antibodies, including J8 and J9 (Durham et al., 2019). After defining the conformations stabilized by these antibodies, we can rationally design and characterize antigens with reduced dynamics and stable exposure of protective E epitopes.  Our aim is to elicit broadly protective antibodies with minimal serotype-specific or non-neutralizing pathogenic responses associated with antibody-dependent enhancement (ADE) of infection and severe disease in individuals with pre-existing DENV immunity.  Similarly, we will translate our mechanistic findings from other aspects of viral replication into a dynamics-based approach to rationally engineer interventions where traditional approaches have been challenging.

    Our research approach is relevant and adaptable to other Class II viral fusogens which share structural and mechanistic features with DENV E. My initial studies on DENV E will lay the groundwork for long-term projects on other aspects of DENV entry and immunity.  This work will also generate novel tools and information on prototype pathogens for pandemic preparedness, directly informing strategies to develop medical countermeasures against viruses with pandemic potential.



    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Durham ND, Jain A, Howard A, Luban J, Munro JB. Molecular basis for the increased fusion activity of the Ebola virus glycoprotein epidemic variant A82V: Insights from simulations and experiments. Cell Rep. 2025 Apr 22; 44(4):115521. PMID: 40186866.
      Citations:    
    2. D?az-Salinas MA, Jain A, Durham ND, Munro JB. Single-molecule imaging reveals allosteric stimulation of SARS-CoV-2 spike receptor binding domain by host sialic acid. Sci Adv. 2024 Jul 19; 10(29):eadk4920. PMID: 39018397.
      Citations:    
    3. Vaknin A, Grossman A, Durham ND, Lupovitz I, Goren S, Golani G, Roichman Y, Munro JB, Sorkin R. Ebola Virus Glycoprotein Strongly Binds to Membranes in the Absence of Receptor Engagement. ACS Infect Dis. 2024 05 10; 10(5):1590-1601. PMID: 38684073.
      Citations:    
    4. Jain A, Govindan R, Berkman AR, Luban J, D?az-Salinas MA, Durham ND, Munro JB. Regulation of Ebola GP conformation and membrane binding by the chemical environment of the late endosome. PLoS Pathog. 2023 Dec; 19(12):e1011848. PMID: 38055723.
      Citations:    Fields:    Translation:HumansCells
    5. Jain A, Govindan R, Berkman A, Luban J, Durham ND, Munro J. Regulation of Ebola GP conformation and membrane binding by the chemical environment of the late endosome. bioRxiv. 2023 Oct 17. PMID: 36711925.
      Citations:    
    6. Soare AY, Malik HS, Durham ND, Freeman TL, Alvarez R, Patel F, Satija N, Upadhyay C, Hioe CE, Chen BK, Swartz TH. P2X1 Selective Antagonists Block HIV-1 Infection through Inhibition of Envelope Conformation-Dependent Fusion. J Virol. 2020 02 28; 94(6). PMID: 31852781.
      Citations: 10     Fields:    Translation:HumansCells
    7. Das DK, Bulow U, Diehl WE, Durham ND, Senjobe F, Chandran K, Luban J, Munro JB. Conformational changes in the Ebola virus membrane fusion machine induced by pH, Ca2+, and receptor binding. PLoS Biol. 2020 02; 18(2):e3000626. PMID: 32040508.
      Citations: 41     Fields:    Translation:HumansCells
    8. Durham ND, Howard AR, Govindan R, Senjobe F, Fels JM, Diehl WE, Luban J, Chandran K, Munro JB. Real-Time Analysis of Individual Ebola Virus Glycoproteins Reveals Pre-Fusion, Entry-Relevant Conformational Dynamics. Viruses. 2020 01 15; 12(1). PMID: 31952255.
      Citations: 10     Fields:    Translation:HumansCells
    9. Durham ND, Agrawal A, Waltari E, Croote D, Zanini F, Fouch M, Davidson E, Smith O, Carabajal E, Pak JE, Doranz BJ, Robinson M, Sanz AM, Albornoz LL, Rosso F, Einav S, Quake SR, McCutcheon KM, Goo L. Broadly neutralizing human antibodies against dengue virus identified by single B cell transcriptomics. Elife. 2019 12 10; 8. PMID: 31820734.
      Citations: 26     Fields:    Translation:HumansCells
    10. Soare AY, Durham ND, Gopal R, Tweel B, Hoffman KW, Brown JA, O'Brien M, Bhardwaj N, Lim JK, Chen BK, Swartz TH. P2X Antagonists Inhibit HIV-1 Productive Infection and Inflammatory Cytokines Interleukin-10 (IL-10) and IL-1? in a Human Tonsil Explant Model. J Virol. 2019 01 01; 93(1). PMID: 30305360.
      Citations: 18     Fields:    Translation:HumansCells
    11. Alvarez RA, Maestre AM, Law K, Durham ND, Barria MI, Ishii-Watabe A, Tada M, Kapoor M, Hotta MT, Rodriguez-Caprio G, Fierer DS, Fernandez-Sesma A, Simon V, Chen BK. Enhanced FCGR2A and FCGR3A signaling by HIV viremic controller IgG. JCI Insight. 2017 02 23; 2(4):e88226. PMID: 28239647.
      Citations: 7     Fields:    Translation:HumansCells
    12. Watanabe SM, Simon V, Durham ND, Kemp BR, Machihara S, Kemal KS, Shi B, Foley B, Li H, Chen BK, Weiser B, Burger H, Anastos K, Chen C, Carter CA. The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility. Retrovirology. 2016 09 06; 13(1):64. PMID: 27600154.
      Citations: 4     Fields:    Translation:HumansCells
    13. Esposito AM, Cheung P, Swartz TH, Li H, Tsibane T, Durham ND, Basler CF, Felsenfeld DP, Chen BK. A high throughput Cre-lox activated viral membrane fusion assay identifies pharmacological inhibitors of HIV entry. Virology. 2016 Mar; 490:6-16. PMID: 26803470.
      Citations: 12     Fields:    Translation:HumansCells
    14. Durham ND, Chen BK. Measuring T Cell-to-T Cell HIV-1 Transfer, Viral Fusion, and Infection Using Flow Cytometry. Methods Mol Biol. 2016; 1354:21-38. PMID: 26714702.
      Citations: 8     Fields:    Translation:HumansAnimalsCells
    15. Durham ND, Chen BK. HIV-1 Cell-Free and Cell-to-Cell Infections Are Differentially Regulated by Distinct Determinants in the Env gp41 Cytoplasmic Tail. J Virol. 2015 Sep; 89(18):9324-37. PMID: 26136566.
      Citations: 18     Fields:    Translation:HumansCells
    16. Swartz TH, Esposito AM, Durham ND, Hartmann BM, Chen BK. P2X-selective purinergic antagonists are strong inhibitors of HIV-1 fusion during both cell-to-cell and cell-free infection. J Virol. 2014 Oct; 88(19):11504-15. PMID: 25031337.
      Citations: 29     Fields:    Translation:HumansCells
    17. Micsenyi AM, Zony C, Alvarez RA, Durham ND, Chen BK, Klotman ME. Postintegration HIV-1 infection of cervical epithelial cells mediates contact-dependent productive infection of T cells. J Infect Dis. 2013 Dec 01; 208(11):1756-67. PMID: 23908485.
      Citations: 16     Fields:    Translation:HumansCells
    18. Durham ND, Yewdall AW, Chen P, Lee R, Zony C, Robinson JE, Chen BK. Neutralization resistance of virological synapse-mediated HIV-1 Infection is regulated by the gp41 cytoplasmic tail. J Virol. 2012 Jul; 86(14):7484-95. PMID: 22553332.
      Citations: 47     Fields:    Translation:HumansCells
    19. Ramos I, Bernal-Rubio D, Durham N, Belicha-Villanueva A, Lowen AC, Steel J, Fernandez-Sesma A. Effects of receptor binding specificity of avian influenza virus on the human innate immune response. J Virol. 2011 May; 85(9):4421-31. PMID: 21345953.
      Citations: 46     Fields:    Translation:HumansAnimalsCells
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