Dr CJ Anderson
My lab focuses on the interactions between intestinal microbes and dying epithelial cells during injury and repair using both microbe and host-centric approaches.
Dr CJ Anderson
Wellcome Trust Career Development Fellow
Background
The threat from microbes, both external and internal, is constant. Every year, the World Health Organization estimates that foodborne infections alone account for 600 million cases. The human body, which itself comprises an estimated 30 trillion cells, is also home to approximately 38 trillion bacterial cells, with the majority of these bacteria residing within the intestine. Detrimental shifts in this commensal population, termed dysbiosis, can have vastly unfavourable effects on health.
One of the most common traits of intestinal dysbiosis is the expansion of the Gram-negative Enterobacteriaceae family of organisms. For example, patients with inflammatory bowel disease or cancer patients receiving cytotoxic chemotherapy develop cycles of intestinal dysbiosis, with particular expansion of the Enterobacteriaceae, that correlate with levels of intestinal inflammation and disease. Further, chemotherapy-induced gastrointestinal toxicity leaves patients susceptible to invasive bacterial infections and frequently drives premature cessation of treatment leading to a reduction in therapeutic efficacy. Although the correlation between dysbiosis and intestinal pathology is well documented in various clinical settings, the underlying mechanisms remain largely undefined. Therefore, it is essential to understand the mammalian and bacterial factors that contribute to infections and dysbiosis to develop novel therapeutic approaches that reduce susceptibility to infection and limit intestinal injury associated with Enterobacteriaceae dysbiosis, particularly with antibiotic resistance continuing to rise.
Apoptosis is a major form of programmed cell death, and apoptotic cells produce soluble factors that communicate with the surrounding tissue. During my postdoctoral work, I identified a mechanism by which intestinal Enterobacteriaceae directly exploit the soluble molecules released by apoptotic mammalian epithelial cells. The soluble metabolites derived from apoptotic intestinal epithelial cells are necessary and sufficient to promote the outgrowth of intestinal Enterobacteriaceae, a process termed death-induced nutrient release (DINNR). These findings hold true within the context of foodborne infection, inflammation-related disease, and chemotherapy-induced mucositis in vivo, and are consistent across infections (Salmonella or Escherichia coli) and dysbiosis.
Research Overview
My lab uses both host and microbe-centric approaches to identify the critical points of communication between intestinal bacterial and mammalian epithelial cells. We combine bacterial RNA sequencing with unbiased metabolomic profiling of host cell supernatants in our in vitro and ex vivo reductionist approaches to identify candidate pathways/molecules of interest. From there, we harness the power of bacterial genetics and apply our findings to in vivo models of murine infection, inflammatory disorders, and chemotherapy treatment.
Experimental toolbox: bacterial genetics, RNA sequencing/qPCR, metatranscriptomics, metabolomics, mammalian cell culture, mammalian genetics, microscopy, flow cytometry, mouse models.
Biographical Profile
I graduated with a BS in Biology from the University of Wisconsin (USA) in 2011. From there, I spent the next 2 years in a clinical microbiology and infectious disease research laboratory that focused on molecular diagnostics for bloodstream, urinary tract, and intestinal tract infections. I returned to academia and completed my PhD in microbiology (2013-2017) in the lab of Professor Melissa Kendall at the University of Virginia (USA) studying bacterial signal transduction networks during host adaptation. I was awarded membership to the Raven Society and received the MIC Outstanding Student Award. After my PhD, I was awarded a Postdoctoral Fellowship from the Belgian government to work with Professor Kodi Ravichandran at the VIB-UGent Center for Inflammation Research (2018-2023). There, my work identified a novel relationship in which intestinal microbes exploit the soluble factors released by dying mammalian cells. In October 2022, I was awarded the Chancellor’s Fellowship and subsequently the Wellcome Trust Career Development Award to establish my own lab within the CIR.
Team Members
- Sebastian Rogatti Granados - Lab Technician
- Sam Benson, PhD - Postdoctoral Research Assistant
- Anna Davey - Ker Memorial PhD Student
- Priscilla Chin, PhD - Lab Technician
- Mariska Simpson, PhD - Postdoctoral Research Assistant
Honours and Awards
- 2022 Chancellor’s Fellowship – University of Edinburgh (UK)
- 2021 Young Investigator Proof-of-Concept Grant – Cancer Research Institute Gent (Belgium)
- 2018 Peach & Hungerford Award Finalist - University of Virginia (USA)
- 2018 MIC Department Outstanding Student - University of Virginia (USA)
- 2017 Raven Society Scholarship - University of Virginia (USA)
- 2012 Service Values Award - Northshore University HealthSystem (USA)
Other Responsibilities
- American Society for Microbiology Future Leaders Mentoring Fellowship (Mentor)
- The Social Scientist (Mentor)
- Badger Bridge (Mentor)
- Global Biotech Revolution Connect (Mentor)
Collaborators
Internal
External
- Professor Melissa Kendall University of Virginia USA
- Professor Justin Perry Memorial Sloan Kettering, USA
- Professor Charlotte Scott VIB-UGent, Belgium
- Professor Lars Vereecke VIB-UGent, Belgium
Funding
Wellcome Trust Career Development Award (2023-2031)
Publications