Carabeo Lab

The Carabeo laboratory conducts research on the interaction of the human pathogen Chlamydia trachomatis with the mucosal epithelium. Three major research questions we are addressing are:

How does Chlamydia invade non-phagocytic epithelial cells?

Chlamydiae are obligate intracellular bacteria. They require an intracellular niche for growth and replication. Therefore, access to this niche is paramount to their survival and absolutely required to initiate disease. Epithelial cells do not take up particles efficiently, and thus must be stimulated to remodel the cortical cytoskeleton to phagocytose particles, like Chlamydia elementary bodies. The molecular mechanism of Chlamydia invasion has been a long-standing interest in my lab, and we have made significant contributions in obtaining a mechanistic view of this process at the molecular level, including the identification of TarP, and elucidation of its function as a signaling scaffold to which multiple signal transduction pathway emanate, activating the actin cytoskeleton remodeling machinery. We continue our research on TarP and the role of contractile forces within the cell in regulating its signaling activity. We use quantitative fluorescence imaging to measure the dynamics of formation of the signaling complex. We also employ super-resolution microscopy to visualize the arrangements of various signaling molecules within this complex.

How does infection lead to scarring-related infertility?

A hallmark of advanced Chlamydia infection is fibrosis or scarring, and reproductive complications are often associated with uncontrolled fibrosis. The process of fibrosis involves three major cell types, the immune cells, the epithelial cells, and stromal fibroblasts. Stromal fibroblasts mediate the formation of scars, but they need to be activated to express specific proteins, including collagen, which is the structural component of scars. The prevailing view of fibrosis associated with Chlamydia infection is centered on the robust inflammatory response that cause indiscriminate damage to the epithelium, and repeated damage skews the response of fibroblasts from tissue repair and regeneration to fibrosis. Our research focuses on the role of the epithelium in activating fibroblasts. Unpublished observations indicate that Chlamydia can induce the activation of multiple host transcription factors and their target genes that are known to participate in fibrosis. To address how infection alters the interaction of the epithelial cells with fibroblasts during infection, we use single-cell RNA sequencing, quantitative imaging, and 3D cultures.

How does Chlamydia respond and adapt to iron starvation?

Nutritional immunity is the process of nutrient limitation as part of the host immune response to infection. This typically leads to pathogen starvation to limit its growth and replication. One of the targets of nutritional immunity is iron. Chlamydia is exquisitely sensitive to iron limitation, and thus must possess mechanisms to handle short-term iron limitation in vivo. We have identified a transcriptional regulator in Chlamydia that functions in an iron-dependent manner, i.e. its repressor function depends on sufficient level of iron. We also have characterized the iron-responsive regulon of Chlamydia, thus giving us insight into the initial responses of the bacteria as soon as it senses iron depletion. We determined that part of the response overlaps with the tryptophan starvation response, raising the intriguing possibility of an integrated response. This contrasts with model prokaryotes with larger genomes, which are capable of raising a tailored response to specific stresses. We are now studying the molecular basis of this integrated responses to iron and tryptophan limitation. We use a systems biology approach to determine genome-wide alterations to changes in transcription (single-cell and batch RNA sequencing), ribosomal profiling, and chromatin immunoprecipitation and sequencing (ChIP-seq) to gain in-depth mechanistic insights into gene regulatory changes during development and response to stress.


Lab Publications



Lab Personnel


Dr. Rey Carabeo – Professor
BS, University of California, Los Angeles
PhD, University of Wisconsin-Madison
Postdoctoral training – Rocky Mountain Laboratory, NIAID



Dr. Amanda Brinkworth – Assistant Professor
BS, Indiana University – Bloomington
PhD, University of Louisville Medical School
Postdoctoral training – Washington State University

Research project – Immune evasion strategies of Chlamydia trachomatis with a focus on attenuation of cytokine signaling in infected epithelial cells




Dr. Nick Pokorzynski – Postdoctoral Research Associate
BS, Michigan State University
PhD, Washington State University

Research project – Transcriptional regulatory responses of Chlamydia trachomatis to iron and tryptophan starvation.




Liam Caven – PhD student
BS, University of California, San Diego

Research project – The mechanism of epithelial-to-mesenchymal transition of Chlamydia-infected epithelial cells and its relationship to fibrosis




Korinn Murphy – PhD student
BA, Willamette University

Research project – Modulation by Chlamydia trachomatis of host cell adhesion to the extracellular matrix to counteract epithelial cell extrusion




Matthew Romero – PhD student
BS, MS, Texas Tech University

Research project – Establishment of a mechanosensitive landscape during invasion of epithelial cells by Chlamydia trachomatis




Amanda Stastny – PhD student
BS, University of Nebraska – Lincoln

Research project – Functional regulation of the chlamydial iron-dependent transcriptional repressor YtgR by site-specific proteolytic cleavage




Francis Fontanilla – PhD student
BS, Far Eastern University, Manila
MS, University of the Philippines

Research project – Bystander effects of Chlamydia infection on neighboring epithelial cells and their role in modulating dissemination dynamics