SEP 10, 2020 7:30 AM PDT

Keynote Presentation: Discovery of a gene-microbiome interaction in lung cancer: lessons learned and future directions

C.E. Credits: P.A.C.E. CE Florida CE
Speaker
  • Assistant Professor, Baylor University
    Biography

      Dr. K. Leigh Greathouse is an Assistant Professor at Baylor University with appointments in Biology and Nutrition. Her background spands the fields of cancer biology, epidemiology, and nutrition. She recived her Ph.D. from the University of Texas and M.D. Anderson Cancer Center, and her M.P.H. from Johns Hopkins Bloomberg School of Public Health. She completed her postdoctoral training at the National Cancer Institute in the laboratory of Curtis Harris, where she discovered a novel microbiome-gene interaction in lung cancer. The focus of her laboratory at Baylor is on elucidating the relationship between diet and the microbiome and its impact on cancer etiology and treatment. The goals of the Greathouse lab are focused on 1) delineating the dietary factors that modify the microbiome and its function, 2) developing microbial multi-omic classifiers that improve stratification of patients for cancer treatment, and 3) identify key functional pathways and mechanisms of microbiota-host communication. Dr. Greathouse has received multiple awards for her work, including a Merit Award from the National Insitutes of Health, Excellence in Research Leadership, and Rising Star at Baylor Univeristy. Most recenlty, she was awarded a career development award from Department of Defense to study the relationsihp between diet and the microbiome in colon cancer treatment response and toxicity. Ultimately, the goal of her lab is to discover dietary factors and microbial targets for the development of clinical tools to prevent cancer development, and reduce morbidity and mortality from colon cancer.


    Abstract

    The selective pressure placed on the resident microbiota by local changes in the host environment – DNA damage, chronic inflammation, metabolic shifts, barrier damage, reduced immunosurveillance – might make tumor microenvironment a perfect niche for certain bacterial clades. While bacteria have long been known to play a role in carcinogenesis, only a few have been identified as initiators. In this work we uncover a unique microbiome-gene interaction in lung cancer, between the tumor suppressor gene TP53 and a consortia of bacteria. One taxa in particular, Acidovorax, we discovered was highly abundant in smokers, the primary risk factor for lung cancer. Knowing that mutations in TP53 are prevalent in 70-80% of squamous cell carcinoma (SCC), and confer reduced barrier function, we found that mutations in TP53 were associated with higher Acidovorax in SCC tumors. Further, preliminary data show that Acidovorax temperans administered by nasal instillation accelerates lung tumorigenesis and is detrimental to the survival of a mouse model of adenocarcinoma driven by AdCre-activated Kras and mutant Trp53. Importantly, A. temperans, has the ability to degrade hydrocarbons, such as those found in tobacco smoke, which strongly suggests that microbial metabolism impacts host cellular metabolism and pharmacokinetics. In conducting this research, many lessons were learned, especially in regards to collecting and analyzing low biomass samples. These lessons will be conveyed as critical concepts in human microbiome research and guidelines will be presented for future research studies.

    Learning Objectives:

    1. Define the main confounders in low-biomass microbiome studies

    2. List the key controls you need in human low-biomass studies

    3. Name at least two additional methods required to demonstrate ‘proof of life’ beyond sequencing in human microbiome studies


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