MIP Research in the Spotlight

Studying a protein modification process in worms provides potential insights for human health

A recent study from graduate student Mirella Hernadez-Lima and the Truttmann laboratory found that organisms respond to their environment by changing how several proteins interact through post-translational modifications. They found that AMPylation is important to control the function of a group of proteins called Transforming Growth Factor-β (TGF-β) in neurons of the roundworm Caenorhabditis elegans. Too much AMPylation can affect the growth, reproduction, and sense of smell of worms, and can impair their ability to avoid harmful food sources.

Read more and find a link to the article on M Health Lab here: https://www.michiganmedicine.org/health-lab/studying-protein-modification-processworms-provides-potential-insights-human-health

High levels of ammonia in colon tumors inhibits T cell growth and response to immunotherapy

High levels of ammonia in tumors can inhibit the growth and function of T cells, leading to immunotherapy resistance in mouse models of colorectal cancer, according to new research from MIP MD/PhD student Hannah Bell and the Shah lab, in collaboration with the Lyssiotis lab. The study found that reducing ammonia levels using FDA-approved drugs for hyperammonemia can reduce tumor size in several different models, including metastatic colorectal cancer, and the treatment also synergizes with immunotherapy. The research suggests that tumors have lost the ability to detoxify ammonia leading to build up, and this mechanism could explain resistance in tumors beyond colon cancer. “Only about 20-30% of all cancer patients are sensitive to immunotherapy. 70% of patients don’t derive any benefit from it,” Shah said. “Now, we have a mechanism that could explain this resistance in tumors beyond colon cancer.”

Read more and find a link to the article on M Health Lab here: https://www.michiganmedicine.org/health-lab/high-levels-ammonia-colon-tumorsinhibits-t-cell-growth-and-response-immunotherapy

Researchers in the Rui lab have been investigating the root causes of liver fibrosis to identify potential drug targets for developing new therapies. Lab members Zhiguo Zhang, Xiao Zhong, Hong Shen identified a protein called NIK that is highly activated in malfunctioning bile duct cells, leading to the excessive cell growth and bile duct scarring. Using a genetically modified mouse model, they removed the NIK gene inside the bile duct cells which prevented this ductular reaction and excessive scarring. The team hopes to develop new NIK inhibitors to turn off this liver scarring process and also plan to use the findings to develop a therapy for cholangiocarcinoma, a type of liver cancer which currently has very limited treatment options.

Read more and find a link to the article on M Health Lab here: https://www.michiganmedicine.org/health-lab/molecule-could-be-behind-liver-fibrosis

Researchers interested in aging have long been studying the lifeextending effects of dietary restriction and fasting. A new study from the Leiser Lab, led by Shijaio Huang and Hillary Miller Warrington, investigated why attractive food smells can blunt the life-extending effect of a restricted diet. They found that attractive food smells reduce the activation of the fmo-2 gene, which is involved in lifespan extension in the roundworm C. elegans, and screened compounds that could prevent this reversal. Three compounds, including an antidepressant and two antipsychotic drugs used in humans, were found to enable the life extension effect of FMO proteins, even in the presence of the smell of food. While these specific drugs are unlikely to be prescribed for this effect, they provide important clues about the fmo-2 activation pathway and its effect on lifespan extension.

Read more and find a link to the article on M Health Lab here: https://www.michiganmedicine.org/health-lab/smell-food-blocks-life-extending-effectrestricted-diet-these-drugs-may-unblock-it