This Immune Booster episode features an interview with Justin Wilson, Assistant Professor of Immunobiology at the University of Arizona College of Medicine. Wilson recounts his scientific journey, from early interests in genetics and microbiology to his specialized work in immunology. He details his graduate research on Francisella tularensis, highlighting its immune evasion mechanisms, particularly the role of prostaglandin E2 (PGE2) in skewing T-cell responses and downregulating macrophage antigen presentation. His postdoctoral work at Jenny Ting's lab pivoted to the study of innate immune sensors (NLRs) in the context of gut inflammation, inflammatory bowel disease (IBD), and cancer.
Wilson elaborates on his findings regarding two specific NLRs: NLRP12, an inhibitor of NF-kappaB whose absence leads to exacerbated inflammation and changes in gut microbiota (specifically, depletion of Lachnospiraceae), and AIM2, a DNA sensor found to suppress colon cancer independently of inflammasome activation by targeting the PI3 Kinase AKT pathway. His current lab focuses on AIM2's role in gut epithelial cell differentiation, particularly its impact on "tough cells," a unique epithelial population crucial for gut homeostasis, responses to parasitic infections, and tumor immunity. He also touches upon emerging research on the oral microbiome's connection to inflammation and carcinogenesis, concluding with valuable advice for aspiring scientists on passion, collaboration, and networking.
Journey into Immunological Research & Discoveries:
0:00 Early Scientific Journey: Justin Wilson, Assistant Professor at the University of Arizona College of Medicine, shares his path from a small Vermont town to becoming an immunologist, initially focusing on genetics and microbiology.
1:30 Foundational Lab Experience: His first job as a lab technician involved culturing soil bacteria, providing essential hands-on experience in pipetting and dilutions, and revealing his desire for more in-depth research.
2:45 Graduate Research on Francisella tularensis: Wilson joined a lab studying Francisella tularensis, a bacterium weaponized during the Cold War, focusing on how it evades macrophage defenses by inducing a Cox-2 response and excessive PGE2, which skews T-cell responses and downregulates MHC class II.
7:31 Pivot to Innate Immune Sensors (NLRs): For his postdoctoral work, Wilson transitioned to Jenny Ting's lab, where he explored gut inflammation, IBD, and cancer, focusing on NLRs—intracellular sensors that detect microbial components and cellular damage.
9:50 NLRP12 and Microbiome Homeostasis: His research on NLRP12 revealed its role as a potent inhibitor of NF-kappaB. Its absence in mice led to excessive gut inflammation, increased IBD, and cancer, alongside dysbiosis marked by depleted Lachnospiraceae bacteria, which, when replenished, helped reduce inflammation.
13:54 AIM2's Role in Colon Cancer Suppression: Wilson's work on AIM2, a double-stranded DNA sensor, demonstrated its ability to suppress colon cancer via an inflammasome-independent mechanism, by limiting the activation of the PI3 Kinase AKT cell survival pathway.
15:48 Current Lab's Focus on Gut Epithelial Cells and "Tough Cells": At the University of Arizona, his lab investigates AIM2's role in gut epithelial cell differentiation using 3D organoid cultures. They discovered that AIM2 deletion leads to a loss of "tough cells," a critical epithelial population involved in responding to parasitic infections and influencing IBD and tumor immunity.
21:14 Emerging Oral Cavity Research: The lab is also expanding its research to the oral cavity, studying how oral microbes and the immune system interact and how specific oral streptococci species are linked to inflammation and carcinogenesis.
21:56 Advice for Trainees: Wilson advises aspiring scientists to pursue their passions, find projects that genuinely excite them, build a supportive network of colleagues, and actively participate in conferences to foster collaborations and discover new insights.