Sean Diehl, Ph.D.

Assistant Professor

Training & Education

Dr. Diehl received his Ph.D. in 2003 from The University of Vermont, studying the transcriptional mechanisms of CD4 T cell differentiation. For postdoctoral research, he studied human B cell differentiation and development of antibody therapeutics with Dr. Hergen Spits at the University of Amsterdam. From 2008-2013, Dr. Diehl was a faculty member in the Department of Medicine with research projects encompassing autoimmunity, asthma, infectious disease, and vaccine development in collaboration with the Vaccine Testing Center from 2013-2018.  Dr. Diehl joined the Department of Microbiology and Molecular Genetics in 2018 and continues his research towards developing novel correlates of protection for Dengue, Zika, and rotavirus.

Research Interests

In my lab we seek to understand how infectious agents engage the human immune system and impart long-term memory. This knowledge is critical to developing better vaccines and to developing better laboratory tests to determine if vaccine candidates engage the immune system in a way that is likely to lead to protection. We primarily focus on dengue and zika virus and draw upon an extensive bank of human vaccine clinical trial specimens and natural infection studies. Techniques we use: human cell culture, virus neutralization,  flow cytometry, microscopy, immunoblotting, genomic methods (transcriptomics, PCR, sequencing), molecular cloning.

Current research projects (Funding/Collaborators)
1) Defining cellular immunogenicity for dengue vaccine formulations (Bill and Melinda Gates Foundation, NIH COBRE). 
2) Influence of serostatus on dengue vaccine immunogenicity (NIH COBRE)
3) Defining B cell memory to Dengue and Zika and developing potent neutralizing antibodies (CDC and NIH, Collaboration with A. De Silva, University of North Carolina, Chapel Hill).  
4) Transcriptional profiling of DENV virus infection (Joint College of Medicine/Engineering Biomedical Engineering grant with Donna Rizzo and John Hanley from UVM and Sam Scarpino from Northeastern). 
5) Cellular and molecular characterization of dengue-associated rash (Merck, pending).

Diagram showing genetic reprogramming of memory B cells to interrogate human antibody response to infection

Teaching

Courses:
LCOM Foundations of Clinical Science – Lecturer
MMG 320 (Cellular Microbiology) – Lecturer
MLRS310 (Advanced Immunology) – Lecturer

Philosophy:
My teaching philosophy is that content is best retained and recalled through high in-class involvement, anchoring to relevant examples, and interactive active learning approaches. In my lectures, I reference cutting-edge research across fields, employ group-oriented case studies, and inspire real-time content adeptness through interactive, online quiz competitions. I try to keep my delivery of the material fun in the hope that this fun will become infectious to students and inspire them to do their best. 

Featured Publications

Whitehead SS, Durbin AP, Pierce KK, Elwood D, Fraser EJ, Carmolli MP, Tibery CM, Hynes NA, Jo M, Lovchik JM, Larsson CJ, Doty EA, Dickson DM, Luke CJ, Subbarao K, Diehl SA*, and Kirkpatrick BD*. In a Randomized Trial The Live Attenuated Tetravalent Dengue Vaccine TV003 Is Well-Tolerated and Highly Immunogenic in Subjects with Flavivirus Exposure Prior To Vaccination. PLoS Neglected Tropical Diseases. 2017 11(5): e0005584.*co-senior author. PMCID: PMC5436874

Kirkpatrick BD, Whitehead SS, Pierce KK, Tibery CM, Grier PL, Hynes NA, Larsson CJ, Sabundayo BP, Talaat KR, Janiak A, Carmolli MP, Luke CJ, Diehl SA, Durbin AP. The live attenuated dengue vaccine TV003 elicits complete protection against dengue in a human challenge model. Sci Transl Med. 2016 Mar 16;8(330):330ra36. PubMed PMID: 27089205. NIHMSID: 877588.

Kwakkenbos MJ, Diehl SA*, Yasuda E, Bakker AQ, van Geelen CM, Lukens MV, van Bleek GM, Widjojoatmodjo MN, Bogers WM, Mei H, Radbruch A, Scheeren FA, Spits H, Beaumont T. Generation of stable monoclonal antibody-producing B cell receptor-positive human memory B cells by genetic programming. Nat Med. 2010 16(1):123-8. PMCID: PMC2861345.
*co-first authors

Angelo MA, Grifoni A, O'Rourke PH, Sidney J, Paul S, Peters B, de Silva AD, Phillips E, Mallal S, Diehl SA, Kirkpatrick BD, Whitehead SS, Durbin AP, Sette A, Weiskopf D. Human CD4+ T Cell Responses to an Attenuated Tetravalent Dengue Vaccine Parallel Those Induced by Natural Infection in Magnitude, HLA Restriction, and Antigen Specificity. J Virol. 2017 Feb 14;91(5). pii: e02147-16. PMCID: PMC5309943

Weiskopf D, Angelo MA, Bangs DJ, Sidney J, Paul S, Peters B, de Silva AD, Lindow JC, Diehl SA, Whitehead S, Durbin A, Kirkpatrick B, Sette A. The human CD8+ T cell responses induced by a live attenuated tetravalent dengue vaccine are directed against highly conserved epitopes. J Virol. 2015 Jan;89(1):120-8. doi: 10.1128/JVI.02129-14. Epub 2014 Oct 15. PubMed PMID: 25320311; PubMed Central PMCID: PMC4301095

 

All Diehl publications

Sean Diehl, PhD

Contact Information

Office: C205A Given

Phone: 802-656-9860

Email

Lab Team

Benjamin McElvany, Senior Research Analyst 
Nancy Graham, Senior Research Analyst
Huy Tu, Graduate Student – Development of humoral immunity to dengue and Zika viruses.
Hannah Hatch, Undergraduate researcher – development of an assay to detect antibody-dependent enhancement (Funded by Nicole J. Ferland award). 
Dylan Koundakjian, Medical student – Induction of B cell responses by DENV-infected monocytes (funded by summer fellowship). 
Nikki Samuelson, Undergraduate researcher