My long-term research program focuses on defining the macrophage immune pathobiology exploited by intracellular bacterial pathogens, with particular emphasis on Ehrlichia chaffeensis, the causative agent of human monocytic ehrlichiosis (HME). HME is an emerging, potentially fatal tick-borne disease and represents the most prevalent life-threatening tick-borne zoonosis in the United States. Despite its clinical importance, the molecular mechanisms by which E. chaffeensis subverts host innate immune defenses remain poorly understood. Addressing this critical knowledge gap is essential for identifying novel therapeutic targets for HME, a disease for which no vaccine or targeted therapies currently exist.
My research program integrates microbial genetics, molecular and cellular biology, immunology, genomics, and RNA biology–based approaches to define how intracellular bacterial pathogens reprogram macrophage immune responses at the host–pathogen interface. The central objective of this work is to define the pathogen-driven regulatory mechanisms that perturb host transcriptional and post-translational networks, thereby enabling intracellular survival and immune evasion. This work is organized around four interconnected research directions:
1. Bacterial effector regulation of microbe–host interactions – defining how pathogen-secreted effectors manipulate macrophage signaling pathways and immune regulatory networks.
2. Ehrlichia-mediated modulation of host transcriptomes – determining how E. chaffeensis reshapes host transcriptional and mRNA stability programs to suppress antibacterial immune defenses.
3. Exploitation of eukaryotic regulatory pathways for intracellular survival – uncovering host RNA- and protein-regulatory mechanisms hijacked by Ehrlichia to promote intracellular persistence.
4. Genetic dissection of microbial pathogenesis and immune evasion – leveraging complementary microbial and host genetic approaches to define causal mechanisms underlying immune subversion.
By identifying the molecular determinants of macrophage immune dysfunction during infection, my research seeks to uncover host-directed pathways that can be therapeutically targeted. Ultimately, this work aims to advance fundamental understanding of host–pathogen interactions while enabling the development of innovative, host-directed strategies to combat Ehrlichia infection and related intracellular bacterial diseases.
Ongoing projects that I would like to highlight include:
UTMB-Provost Early Faculty Research Award (EFRA)
“Ehrlichia Modulation of Host Transcriptome for Immune Evasion: Role of hnRNPA2B1-Regulated mRNA Stability.”
(Bui, PI; 75% effort; $200,000 for time period 09/01/2025-08/31/2027)
R01AI192966-NIAID/NIH
“Ehrlichia Modulation of RNA Splicing to Influence KIRREL1-Regulated Hippo Signaling.”
(McBride, PI; 25% effort; for time period 08/01/2025-07/31/2030)