Our lab studies the intersection of bacterial pathogenesis, innate immunity, and cancer. The major topics of ongoing research in the Burke lab are:

Bacterial Pathogenesis:

• Rickettsia pathogenesis & host response: Spotted fever group Rickettsia are tick-borne pathogens that cause serious disease worldwide with increasing incidence and no available vaccines. We are investigating the molecular mechanisms by which Rickettsia species cause disease. A major ongoing project is to identify virulence factors with forward genetic screens. Another project focuses on understanding how as obligate cytosolic pathogens Rickettsia pillage metabolites from host cells. We are leveraging this knowledge to develop improved vaccine and therapeutic approaches.
• Human vs mouse innate immune responses to infection: Rickettsia and other arthropod-borne pathogens cause more serious disease in humans than in mice, which can serve as their reservoirs in nature. We are investigating the differences between human and mouse innate immunity to elucidate the molecular explanation for disease. We are leveraging this knowledge to develop improved animal models that better mimic human disease and improved therapeutics to stimulate human innate immunity to better restrict pathogens.
• Developing innovate tools to study infection: We are developing new imaging and genetic technologies to better understand infectious disease. Our lab uses advanced microscopy approaches including in vivo bioluminescence imaging (IVIS) and super-resolution microscopy, as well as novel genetic approaches such as improved transposons to better understand infectious disease. We are applying these technologies to study Rickettsia pathogenesis and host response, and seek to generate innovative tools that are widely applicable to better investigate microbial pathogenesis.

Cancer:

• Understanding and overcoming hurdles in using STING agonists for cancer: Microbiology is intricately linked with cancer, and a major area of overlap is innate immune receptors such as STING. Therapeutically activating STING elicits profound anti-tumor responses in mice, and targeting innate immunity synergizes with T cell targeting therapies like checkpoint inhibitors. Yet, human clinical trials with STING agonists failed to meet endpoint criteria. We are asking – why? And, how can we improve these therapies?
• Novel STING agonists for cancer: We have discovered novel strategies to potently activate innate immunity in tumors with bacteria. We are now leveraging this foundational knowledge to develop small molecule cancer drugs that robustly stimulate innate immunity for cancer immunotherapy. These studies use mouse models, pharmacology, and chemical synthesis to advance novel small molecule drugs down the preclinical pipeline.
• Microbial cancer therapies & tumor microbiomes: Bacteria can be used therapeutically to target tumors and deliver drug payloads. Moreover, tumors are naturally colonized by bacteria. We’re investigating how to leverage microbes for improved tumor targeting and how tumor microbiomes impact the response to cancer therapies. We recently showed that bacteria can potently activate innate immunity in tumors, providing a blueprint for how to engineer improved microbial and small molecule-based cancer therapies.

Welcome to Orange County, California!

About UC Irvine: The city of Irvine is situated in Orange County, 40 minutes south of Los Angeles and an hour North of San Diego. The UC Irvine campus is just a 10 minute drive to the coast, where you can find Laguna beach, Newport beach and Crystal Cove State Park. The OC is a fantastic area for biking, hiking, surfing, sailing, and for year-round outdoor running or exercising. The OC has an amazing food scene and Irvine is very family-friendly, consistently rated as one of the safest cities in America and just 20 mins away from Disneyland. Read more about UC Irvine here!

Microbiology & Molecular Genetics Department