Cedars-Sinai, Rutgers, Michigan and Baylor Receive $10M NIH Grant to Study Processes of Tissue Repair

Newswise — LOS ANGELES (Oct. 14, 2024) -- Investigators at Cedars-Sinai Guerin Children's and other institutions have been awarded a $10 million grant from the National Institutes of Health (NIH) over five years to explore how adult intestinal tissues revert to an early fetal-like state to heal from injuries.

The research project brings together scientists from Cedars-Sinai, Baylor College of Medicine, the University of Michigan and Rutgers University. The investigators will study a process called fetal reversion, also known as developmental reprogramming, in mouse intestines to understand how adult tissues repair themselves, enabling the creation of a detailed map of healing processes.

“Our goal is to explore whether we can use what we learn about fetal reversion to identify a better way to repair and heal organs such as the intestine,” said Ophir Klein, MD, PhD, executive director of Cedars-Sinai Guerin Children’s and the David and Meredith Kaplan Distinguished Chair in Children’s Health.

The research team includes experts in basic science, regenerative medicine, intestinal physiology, virology, drug screening, and genomics and epigenomics. Their endeavor is called the “Consortium on Intestinal Regeneration and Fetal Reversion: from Atlas to Therapy.”

The Cedars-Sinai Newsroom recently spoke with Klein, the project’s coordinating principal investigator, to learn more about the five-year grant, the team’s research goals and how the grant will help advance our understanding of injury repair.

Can you provide a high-level overview of the team’s research interests and how this grant supports its ongoing work?

The fundamental question that we're interested in understanding is how adult tissues repair themselves. We are using the intestine as our model, and we believe that many elements of the repair processes we discover will be more generalizable beyond the intestine and have implications for other organs.

This grant from the NIH will provide the necessary resources for our research team to use this information to study how repair programs work in a mouse model and to find new ways to help the body heal. The data from our research will be shared online in a way that is easy to use, so the research community at large can explore it and come up with new ideas and treatments in the future. The insights we stand to gain could pave the way to a paradigm shift in our understanding of gut repair.

What is fetal reversion, and how will this grant help advance the understanding of injury and repair?

Fetal reversion is a regenerative response in which adult tissues reactivate behaviors from their developmental stage to heal from damage or injury, including those induced by infection, radiation treatment or inflammation.

Sometimes, the body heals perfectly well, while other times it doesn't heal at all. With the support of the NIH grant, we aim to understand how the healing process occurs and whether it involves processes used by the normally developing embryo. This understanding is important to lay a foundation for potential new treatments and drugs for wound healing.

How will the findings from this research potentially impact the development of new treatments for intestinal injuries and gut repair?

The fetal reversion process involves turning off aspects of normal gene expression programs and switching to a more fetal-like state. We don’t yet know if fetal reversion happens in all types of intestinal healing or if it occurs only during certain types of repairs.

It’s still a little bit of a mystery how the gut is able to repair itself after various injuries. One interesting approach is to compare intestinal regeneration across different organisms, and this hasn't been systematically studied. Our aim is to map intestinal injury and repair in mouse and human models, study repair programs and find new therapeutic targets using drug screening. A standardized approach to this study with the latest technologies will hopefully provide further insight into wound healing and fill gaps in our understanding of intestinal regeneration.

This is a historic grant for Cedars-Sinai Guerin Children’s. How will these funds advance the work being done in your laboratory and further advance Guerin Children’s commitment to bench-to-bedside care?

Receiving an NIH grant of this scope allows Guerin Children's to continue conducting leading-edge research, advancing the work of our physician-scientists who merge top-notch clinical care with translational and foundational research. At Guerin Children's, we focus on the entire health span and how pediatric medicine influences health beyond childhood. By learning from children’s health, we aim to improve health outcomes for adults. We are grateful to the NIH and our collaborators for helping us advance this science.

Read more on the Cedars-Sinai Blog: Six Questions With Ophir Klein, MD, PhD