TISSUE-MICROBE INTERACTIONS IN THE TUMOR MICRO-ENVIRONMENT
It is routinely cited that bacterial cells in our bodies outnumber our own cells by a factor of 10 to 1. While recent estimates have suggested that this ratio is probably off by an order of magnitude, even by more conservative counting we are still roughly half bacteria by cell number. There is a growing body of evidence that these resident bacteria regulate important aspects of tumor progression and therapy response. We believe there is a critical opportunity to leverage tissue-engineered platforms to study the tissue-microbe interaction dynamics that are challenging or impossible to observe in vivo. We are putting a significant effort into developing the tools and proof-of-concept studies to lead this new direction. Some example projects are listed below.
BACTERIAL MIGRATION WITHIN THE TME
We are interested in the means by which bacteria that are normally non-migratory and harmless, such as the oral Fusobacterium nucleatum, sometimes migrate to and are strongly correlated with cancer in distant sites. We are especially interested in the role of the tumor microenvironment (TME) as an active player in this process, and are analyzing the bi-directional interactions of F. nucleatum with model tumor tissues. This project is in close collaboration with the Slade Laboratory in the Department of Biochemistry at Virginia Tech.
"BACTERIOCRINE" FACTORS IN THE TME
We are intrigued by some of the parallels between processes of tumor stress response, metastasis, and cancer drug resistance, and processes of bacterial quorum-sensing signaling, colonization, and antibiotic resistance. Along these lines we are working to analyze the role of bacterial factors known to regulate bacterial stress response for their potential cross-over role in tumor stress response dynamics. We term such factors as "bacteriocrine factors", and believe these play important roles in several of the well-known hallmarks of cancer.
RECENT RELATED PUBLICATIONS
UTILIZING WHOLE FUSOBACTERIUM GENOMES TO IDENTIFY, CORRECT, AND CHARACTERIZE POTENTIAL VIRULENCE PROTEIN FAMILIES
Ariana Umana, Blake E. Sanders, Christopher C. Yoo, Michael A. Casasanta, Scott S. Verbridge, Daniel J. Slade
Journal of Bacteriology, 2019, 201:e00273-19
N-(3-OXODODECANOYL)-L-HOMOSERINE LACTONE INTERACTIONS IN THE BREAST TUMOR MICROENVIRONMENT: IMPLICATIONS FOR BREAST CANCER VIABILITY AND PROLIFERATION IN VITRO
Brittany N. Balhouse, Logan Patterson, Eva M. Schmelz, Daniel J. Slade, Scott S. Verbridge
PLOS ONE, 2017, v. 12, (7), e0180372
Megan C. Cox, Laura M. Reese, Lissett R. Bickford, Scott S. Verbridge
ACS Biomaterials Science & Engineering, 2015, v. 1, (10), 877-894