Christopher Johnston

Over the last decade, extensive research has uncovered the presence of a distinct microbes within tumors across gastrointestinal tract cancers, which can persist in metastatic disease, and which differ among individual cancer types. Moreover, it has become evident that both the tumor infiltrating microbes and the gut microbiota play a vital role in cancer development, cancer progression, and can influence patients' response to therapies. Over the next decade, for cancer microbiology research to significantly advance cancer knowledge and therapy, it needs to move from correlations of specific microbes with individual cancer types towards studies that provide mechanistic insights on their role in disease. It is within this paradigm shift that novel opportunities for cancer prevention and cure will be revealed. The long-term goal of my research is to gain a comprehensive understanding of the capabilities of tumor-infiltrating bacteria, elucidate the underlying mechanisms driving their behavior, and utilize this knowledge to engineer innovative therapeutics and advanced microbe-based technologies for cancer prevention and treatment. To achieve this, we employ cutting-edge bacterial om1cs techniques (including pangenomics, pan-epigenomics, transcriptomics, and metabolomics) to generate hypotheses centered on understanding how specific microbes migrate to, colonize, and persist within human tumors. We then utilize synthetic microbiology principles to develop genetic systems for these tumor-associated microbes, allowing us to experimentally test and refine our hypotheses using in-vitro and pre-clinical models of disease. Moreover, using knowledge gained, we aim to harness the innate abilities of microbes to access recalcitrant areas of the tumor microenvironment and engineer them as effective delivery vehicles for therapeutic payloads (bugs as drugs). Further, we seek to use precision microbiome engineering to promote favorable response to therapies and improve patient outcomes.