Vaccines and immunology
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.
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 global 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).
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
* indicates equal contribution
Yang R, Lirussi D, Thornton TM, Jelley-Gibbs DM, Diehl SA, Case LK, Madesh M, Taatjes DJ, Teuscher C, Haynes L, Rincón M (2015) Mitochondrial Ca(2+) and membrane potential, an alternative pathway for Interleukin 6 to regulate CD4 cell effector function. Elife 4 in press.
Kirkpatrick BD, Durbin AP, Pierce KK, Carmolli MP, Tibery CM, Grier PL, Hynes N, Diehl SA, Elwood D, Jarvis AP, Sabundayo BP, Lyon CE, Larsson CJ, Jo M, Lovchik JM, Luke CJ, Walsh MC, Fraser EA, Subbarao K, Whitehead SS (2015) Robust and Balanced Immune Responses to All 4 Dengue Virus Serotypes Following Administration of a Single Dose of a Live Attenuated Tetravalent Dengue Vaccine to Healthy, Flavivirus-Naive Adults. J Infect Dis in press.
Kirkpatrick BD, Colgate ER, Mychaleckyj JC, Haque R, Dickson DM, Carmolli MP, Nayak U, Taniuchi M, Naylor C, Qadri F, Ma JZ, Alam M, Walsh MC, Diehl SA, PROVIDE Study Teams, Petri WA Jr (2015) The “Performance of Rotavirus and Oral Polio Vaccines in Developing Countries” (PROVIDE) study: description of methods of an interventional study designed to explore complex biologic problems. Am J Trop Med Hyg 92(4): 744-51.
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.
Ruth L. Kirschstein National Research Service Award (NRSA) F32AI063846 (Diehl, PI) 09/01/2005 – 10/01/2008
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)
Department of Medicine
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Lab: C249 Given
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