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.