Muthusamy Thangaraju
Augusta University, GA·Biochemistry
Bacteria living in the gut have long been linked to protection from colon cancer, but how they help is not well understood. This project focuses on GPR109A, a receptor on cell surfaces.
- Fields
Biochemistry
Medicine & Clinical Research
Microbiology & Immunology
- Topics
colon cancer
colorectal cancer
p53
- Grants
- 1 known grant, through Jun 2028
What they work on
- Determine the role of the GPR109A–p53 axis in colon cancer driven by KRAS mutation, chemical carcinogens and dietary carcinogens, using mice with colon-specific deletion of Gpr109a and p53.
- Uncover how activators of GPR109A, such as niacin and butyrate, switch on the tumor suppressor p53, and test whether they can work as drugs against colon cancers carrying mutant p53.
- Show that gut bacterial metabolites keep normal p53 working and prevent excess immune activation in the colon through GPR109A, using mice lacking Hmgcs2, the rate-limiting enzyme of colonic ketogenesis.
More about the research
It is activated by three molecules: butyrate, made by gut bacteria when they ferment fiber; beta-hydroxybutyrate, a ketone body; and niacin, a vitamin. About 85% of colon cancers show reduced GPR109A levels. The team found that GPR109A levels are inversely linked to colon cancers carrying KRAS mutations; KRAS is a cancer-driving gene. Many colon cancers also have a mutated or inactive p53, a tumor suppressor protein. p53 depends on NAD+, a molecule cells make from niacin.
Why it matters
Niacin is already an FDA-approved drug taken by millions of Americans for cholesterol. This work could show whether niacin and other GPR109A activators might help prevent or treat colon cancer, including tumors with p53 or KRAS mutations. It may also explain how gut bacteria and their metabolites protect against colon cancer. This could point to new prevention strategies based on diet and microbes.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Jennifer Davis
University of Kansas, KS·Medicine & Clinical Research
Test whether tirzepatide, a dual GIP/GLP-1 receptor drug used for diabetes and obesity, lowers colorectal tumor formation and growth when given before tumor induction in diet-fed iKAP (inducible Kras, Apc, p53) mice.
Xinbin Chen
University of California-Davis, CA·Biochemistry
Determine how CDK4/6 enzymes, the RNA-binding protein RBM38 and the protein-synthesis factor eIF4G together boost mutant p53 production, and whether CDK4/6 inhibitors suppress triple-negative breast cancers partly by lowering mutant p53.
Jennifer DuBois
Montana State University, MT·Biochemistry
Determine the structure, function, regulation and molecular interactions of the heme utilization (hmu) pathway in the gut bacterium Bacteroides thetaiotaomicron, and identify its metabolic end products.
The school
Augusta University: 11 labs on PI Pages, $166M a year on research, 37 research doctorates a year.
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