|Education||MS, Idaho State University|
Dr. Steve Dumler
|Current Position||Faculty Member|
Dine’ College – Dine’ College (formerly Navajo Community College)
Anaplasma phagocytophilum is the causative agent of human granulocytic anaplasmosis (HGA).
HGA is a potentially fatal tick borne disease that emerged in the early 1990’s and is now recognized as a wide-spread disease agent across the United States, parts of Europe, and Asia. A. phagocytophilum,an obligate intracellular bacterium in the order Rickettsiales, is one of a few bacteria that can both survive and replicate in neutrophils. Infection promotes alterations in neutrophil function such as decreased antimicrobial responses and an increase in proinflammatory responses. More specifically, infection results in a decrease of superoxide production, inhibition of apoptosis, and increased cytokine/proinflammatory protease production and release. Many of these changes are regulated at the transcriptional level suggesting that the bacterium itself could directly alter gene transcription and cell programming. AnkA is a nuclear toxin released by the bacteria and appears to play an essential role in infection. AnkA is known to bind AT rich regions of DNA including the promoter of CYBB, a component of the NADPH oxidase. Transcription of CYBB decreases over the course of A. phagocytophilum infection concurrent with an increasingly concentration of AnkA in the host cell nucleus. My project involves identifying mechanisms by which AnkA exerts its effects on host transcriptional responses as well as identifying other nuclear toxins that may be produced by the bacterium.
Global DNA methylation changes and differential gene expression in Anaplasma phagocytophilum-infected human neutrophils. Sinclair SH, Yegnasubramanian S, Dumler JS. Clin Epigenetics. 2015 Jul 29;7(1):77. doi: 10.1186/s13148-015-0105-1. eCollection 2015. PMID: 26225157
Comparison and characterization of granulocyte cell models for Anaplasma phagocytophilum infection. Rennoll-Bankert KE, Sinclair SH, Lichay MA, Dumler JS. Pathog Dis. 2014 Jun;71(1):55-64. doi: 10.1111/2049-632X.12111. Epub 2013 Dec 20. PMID:24376092
Chromatin-bound bacterial effector ankyrin A recruits histone deacetylase 1 and modifies host gene expression. Rennoll-Bankert KE, Garcia-Garcia JC, Sinclair SH, Dumler JS. Cell Microbiol. 2015 Nov;17(11):1640-52. doi: 10.1111/cmi.12461. Epub 2015 Jun 11. PMID: 25996657
Effector bottleneck: microbial reprogramming of parasitized host cell transcription by epigenetic remodeling of chromatin structure. Sinclair SH, Rennoll-Bankert KE, Dumler JS. Front Genet. 2014 Aug 14;5:274. doi: 10.3389/fgene.2014.00274. eCollection 2014. Review. PMID:25177343