Vaccines and immunology

Cytoplasmic, punctate distribution of dengue virus (DENV) prM protein in infected cells. Green african monkey kidney cells (Vero) were infected with DENV for two days and stained with an antibody against the prM (pre-membrane) protein of DENV (in green), the actin cytoskeleton (phalloidin, in red), and nuclei (with DAPI, in blues).



Profile

1998, B.S. Biology, State University of New York, Geneseo, NY

2003, PhD, Cell and Molecular Biology, University of Vermont, Burlington, VT
Dissertation: The two faces of Interleukin 6 on T helper 1/2 differentiation

2003-2008, Postdoc, Academic Medical Center, University of Amsterdam, Netherlands
Molecular mechanisms controlling human B cell growth and differentiation.

Research Description

Human immunology, vaccine development

The overarching goal of my research is to define signaling mechanisms that control human T and B cell function in both normal and dysfunctional (i.e. chronic inflammation) states. We study this in the context of in vivo human vaccine responses as well as in defined in vitro culture settings. Through the use of relevant culture models and retroviral delivery of stable genetic modifications we can dissect the molecular mechanisms involved in human T and B cell differentiation and acquisition of effector function. This work is done with a focus on neglected infectious diseases and global health. Current projects aim to 1) understand immunological basis for oral vaccine failure in the context of malnourishment and 2) Cellular and humoral immune responses to vaccination with live-attenuated formulations of Dengue virus (DENV), a vector-borne virus endemic to nearly half the world’s population.

Cytoplasmic, punctate distribution of dengue virus (DENV) prM protein in infected cells. Green african monkey kidney cells (Vero) were infected with DENV for two days and stained with an antibody against the prM (pre-membrane) protein of DENV (in green), the actin cytoskeleton (phalloidin, in red), and nuclei (with DAPI, in blues).

Cytoplasmic, punctate distribution of dengue virus (DENV) prM protein in infected cells. Green african monkey kidney cells (Vero) were infected with DENV for two days and stained with an antibody against the prM (pre-membrane) protein of DENV (in green), the actin cytoskeleton (phalloidin, in red), and nuclei (with DAPI, in blues).

Highlighted Publications

The human CD8+ T cell responses induced by a live attenuated tetravalent dengue vaccine are directed against highly conserved epitopes. 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. J Virol. 2014 Oct 15. pii: JVI.02129-14. [Epub ahead of print] PMID: 25320311 [PubMed – as supplied by publisher] J Virol. 2014 Oct 15. pii: JVI.02129-14. [Epub ahead of print] PMID: 25320311

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. Nature Medicine. 2010 Jan;16(1):123-8

Diehl SA, Schmidlin H, Nagasawa M, Blom B, Spits H. IL-6 triggers IL-21 production by human CD4+ T cells to drive STAT3-dependent plasma cell differentiation in B cells. Immunol Cell Biol. 2012 Sep;90(8):802-11

Diehl SA, Schmidlin H, Nagasawa M, van Haren SD, Kwakkenbos MJ, Yasuda E, Beaumont T, Scheeren FA, Spits H. STAT3-mediated up-regulation of BLIMP1 Is coordinated with BCL6 down-regulation to control human plasma cell differentiation. J Immunol. 2008 Apr 1;180(7):4805-15

Schmidlin H, Diehl SA, Blom B. New insights into the regulation of human B-cell differentiation. Trends Immunol. 2009 Jun;30(6):277-85

Becker PD, Legrand N, van Geelen CM, Noerder M, Huntington ND, Lim A, Yasuda E, Diehl SA, Scheeren FA, Ott M, Weijer K, Wedemeyer H, Di Santo JP, Beaumont T, Guzman CA, Spits H. Generation of human antigen-specific monoclonal IgM antibodies using vaccinated PLoS One. 2010 Oct 4;5(10).

Carbone G, Wilson A, Diehl SA, Bunn J, Cooper SM, Rincon M. Interleukin-6 receptor blockade selectively reduces IL-21 production by CD4 T cells and IgG4 autoantibodies in rheumatoid arthritis. Int J Biol Sci. 2013;9(3):279-88

View all Diehl publications here.

* indicates equal contribution

Recent Publications

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 (2015) The Human CD8+ T Cell Responses Induced by a Live Attenuated Tetravalent Dengue Vaccine Are Directed against Highly Conserved Epitopes. J Virol 89(1): 120-8.

Diehl SA, McElvany B, Noubade R, Seeberger N, Harding B, Spach K, Teuscher C (2014) G proteins Gαi1/3 are critical targets for Bordetella pertussis toxin-induced vasoactive amine sensitization. Infect Immun 82(2): 773-82.

Lahiri T, Guillet A, Diehl S, Ferguson M (2014) High-dose ibuprofen is not associated with increased biomarkers of kidney injury in patients with cystic fibrosis. Pediatr Pulmonol 49(2): 148-53.

Carbone G, Wilson A, Diehl SA, Bunn J, Cooper SM, Rincon M (2013) Interleukin-6 receptor blockade selectively reduces IL-21 production by CD4 T cells and IgG4 autoantibodies in rheumatoid arthritis. Int J Biol Sci 9(3): 279-88.

Diehl SA, Schmidlin H, Nagasawa M, Blom B, Spits H (2012) IL-6 triggers IL-21 production by human CD4+ T cells to drive STAT3-dependent plasma cell differentiation in B cells. Immunol Cell Biol 90(8): 802-11.

Lu C, Diehl SA, Noubade R, Ledoux J, Nelson MT, Spach K, Zachary JF, Blankenhorn EP, Teuscher C (2010) Endothelial histamine H1 receptor signaling reduces blood-brain barrier permeability and susceptibility to autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 107(44): 18967-72.

Nagaleekar VK, Diehl SA, Juncadella I, Charland C, Muthusamy N, Eaton S, Haynes L, Garrett-Sinha LA, Anguita J, Rincón M (2008) IP3 receptor-mediated Ca2+ release in naive CD4 T cells dictates their cytokine program. J Immunol 181(12): 8315-22.

View all Diehl publications here.

Selected Awards

Ruth L. Kirschstein National Research Service Award (NRSA) F32AI063846 (Diehl, PI) 09/01/2005 – 10/01/2008
NIAID
Role of STAT5 and Bcl-xL in human B cell survival.
The goal of the study was to determine whether primary human B cell function, survival, and proliferaton were controlled by activation of transcriptional activators such as STATs, specifically STAT5. Role: PI (2005-2008)


Sean Diehl, Ph.D.

Sean
Diehl, Ph.D.

Assistant Professor
Department of Medicine

 

656-9860
Office: C205A Given
Lab: C249 Given

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