The Optimisticc team is supported through the Cancer Grand Challenges initiative. Learn more here

WP2: Epidemiological correlates of the colorectal cancer microbiome

Colorectal cancer (CRC) most often occurs sporadically (as compared to genetic forms of the disease) and is one of the leading causes of cancer-related death worldwide. Environmental factors contribute substantially to CRC risk and development, particularly the intestinal microbiota. The project overall aims to understand the role of aetiologic factors in tumor development with epidemiologic features in relation to the tumor tissue microbiome. Our work package hypothesis is that Lifestyle risks, environmental exposures, diet, and cancer phenotypes are each associated with features of the colorectal cancer microbiome.

Recently, newer cancer treatments have begun to utilize the tools inherent in our immune system to better treat and control the disease. The immune system plays critical roles in the body’s response to CRC. However, it remains uncertain how this relationship between CRC and immunity differs between various bacteria. The enhancement of the activity of the immune system via changes in various lifestyle behaviors is of great interest.

Unlike genetic factors, both the microbiome and diet are modifiable and represent broadly actionable targets for CRC prevention and therapy. However, neither the causal molecular mechanisms nor corresponding microbes have been pinpointed for CRC. We thus propose to identify metabolic and genetic factors within CRC-associated microbes and their molecular regulatory consequences in the gut. We will perform the first analysis of CRC-associated microbial genetics in the largest collection of human gut microbiomes created to date, spanning over ten different study populations. We will further assess transcriptional regulatory consequences of these microbial genetic variants and their interaction with dietary and lifestyle factors that contribute to CRC.

Work Package Leaders

Curtis Huttenhower, PhD

Curtis Huttenhower, PhD

Co-Investigator, Harvard TH Chan School of Public Health

  • Professor of Computational Biology and Bioinformatics

  • Departments of Biostatistics and Immunology and Infectious Diseases

  • Associate Member, Broad Institute of MIT and Harvard

  • Co-director, Harvard Chan Microbiome in Public Health Center

Shuji Ogino, MD, PhD, MS

Shuji Ogino, MD, PhD, MS

Co-Investigator, JBrigham and Women’s Hospital, Harvard T.H. Chan School of Public Health/ Harvard Medical School Broad Institute of MIT and Harvard

  • Professor of Pathology, Brigham & Women’s Hospital, Harvard Medical School 
  • Professor (Epidemiology), Harvard T.H. Chan School of Public Health                 
  • Chief Program in Molecular Pathological Epidemiology, Brigham and Women’s 
  • Associate Member, Broad Institute of MIT and Harvard
Lee Jones, MBA

Lee Jones, MBA

Patient Advocate

Lee was diagnosed with Stage IV colon cancer in March 2004, and since undergoing several rounds of chemotherapy and a liver resection in July 2006 has been cancer free. Lee has a BA in Psychology and an MBA in Finance and had a successful executive career in government, banking, consulting, and not-for-profit organizations. 

Meet Lee

Learn about other Work Packages

WP1: The Microbiome in colorectal cancer risk

WP1: The Microbiome in colorectal cancer risk

WP1: The Microbiome in colorectal cancer riskWe are analyzing the microbiome of 3000 bowel tumors, to determine the relationship between the bacteria within tumors and their mutations. We have analyzed the microbiome of over 2288 bowel cancer screening samples. Our...

WP 4: Model systems to study the colorectal cancer microbiome

WP 4: Model systems to study the colorectal cancer microbiome

WP4: Model systems to study the colorectal cancer microbiomeThe Clevers lab has been using their human ‘mini-gut’ technology. These mini guts (a.k.a. intestinal organoids) are grown in a dish from healthy gut stem cells. They can be expanded indefinitely and create...

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