Lab Research: The Watson lab is focused on the notorious human pathogen, Mycobacterium tuberculosis, which remains a major global health threat.  M. tuberculosis has evolved a variety of specific adaptations to not only survive but also replicate within the harsh environment inside a macrophage. We want to understand how host macrophages sense and respond to M. tuberculosis and how specific host proteins regulate the outcome of M. tuberculosis infection, both inside macrophages ex vivo and in a mouse model of infection. We have recently started to focus on the interface between mitochondria and M. tuberculosis. Specifically, we are interested in uncovering the molecular mechanisms that explain why mutations in several genes related to mitochondrial function confer susceptibility to M. tuberculosis in humans.

Keywords: Innate immunity, macrophage, mitochondria, immunometabolism, autophagy type I inteferon, gene expression, Mycobacterium tuberculosis, intracellular bacterial pathogens

Dr. Blair’s objective is to identify effective and scalable solutions to rapidly diagnose and appropriately treat severe and emerging infectious diseases in hospitalized and remote settings. With experience working with Department of Defense and international partners, he has described scrub typhus in Uganda, the clinical course and treatment of severe viral illnesses, and point-of-care ultrasound performance in diverse settings. His overall research goal is to address the striking need for tools to facilitate early patient triage and targeted treatments in low-resource and outbreak settings with current projects in the U.S., Uganda, and Peru. His publication history is listed here https://www.ncbi.nlm.nih.gov/myncbi/paul.blair.1/bibliography/public/

Keywords: Communicable Diseases, Emerging; Disease Outbreaks; Diagnostic Techniques and Procedures;Ultrasonography, Interventional

My lab works to elucidate the molecular mechanisms of innate immune regulation in macrophages. While a rapid and robust innate immune response is needed to limit infection, a response that is too strong carries risks like cytokine storm. Therefore, macrophage gene expression needs to be tightly regulated. My lab works to implicate post-transcriptional regulatory mechanisms (e.g., pre-mRNA splicing, mRNA export, RNA decay/turnover, RNA localization etc.) in shaping inflammatory gene expression. We employ a multidisciplinary toolbox of protein and RNA biochemistry, transcriptomics, and microscopy-based approaches to tease apart pathways of interest in mechanistic detail. By highlighting new and unexpected ways that RBPs balance innate immune responses, our work furthers our understanding of how inflammation can be dysregulated during infection and in a variety of human diseases.

Keywords: Innate immunity, macrophage, gene expression, splicing, chromatin, transcription, Mycobacterium tuberculosis, intracellular bacterial pathogens.