# PRDM16 regulation of metabolism in the intestinal stem cell niche

> **NIH NIH K01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $118,862

## Abstract

PROJECT SUMMARY
Long term objectives and training aims: With this award, Dr. Rachel Stine will receive the support, mentorship
and training required to reach her ultimate goal of becoming an independent investigator focused on the
metabolic control of stem cells within the intestinal niche. This research is an excellent fit for the mission of the
NIDDK as it relates to both digestive and metabolic disorders. The University of Pennsylvania offers all of the
scientific resources required to complete this proposal, as well as two exemplary research programs focused
on metabolic studies and intestinal biology respectively. Dr. Stine has assembled a group of renowned
scientists to serve as her mentors, advisory committee and collaborators. She has developed a training plan to
enhance her publication record, to secure independent funding in the form of project grants and to apply for
and secure an independent position by the completion of this award. Dr. Stine’s distinctive research program
seeks to answer basic questions about stem cell biology in the intestine, and will ultimately provide insight into
how alterations in metabolic control of stem cells and their differentiating daughters can lead to a disease state.
Dr. Stine will master techniques essential to her success in this proposal and her future independent research;
integrate and expand her expertise in metabolism and intestinal biology through classes, mentorship and
interactions within the broader scientific community; and build skills to successfully secure an independent
position and start a new laboratory. Background and research aims: Intestinal stem cells have the capacity to
rapidly divide and replenish the intestinal lining every few days. Preliminary studies completed by Dr. Stine
show that deletion of the transcription factor PRDM16 in an adult mouse causes severe intestinal wasting
within five days and death shortly after. RNAseq following Prdm16 deletion shows downregulation of metabolic
genes in the intestinal crypt, particularly members of the fatty acid oxidation (FAO) pathway. Intriguingly,
pharmacological inhibition of FAO blocks budding and growth of intestinal enteroids, specifically in the proximal
small intestine where PRDM16 is highly expressed. Both PRDM16-deficiency and pharmacological inhibition of
FAO can be rescued by supplementation with acetate, which can replenish pools of acetyl-CoA. Aim 1 will
determine which intestinal progenitor cell populations require high levels of PRDM16 and FAO, allowing for
more targeted analysis into how these pathways regulate intestinal differentiation. This aim will also explore
whether mechanisms identified in mice are applicable to a human system. Aim 2 focuses on why FAO
specifically is required for acetyl-CoA production, even in the presence of other nutrients. Because acetyl-CoA
facilitates acetylation of histones, histone profiling as well as genetic perturbations in the acetyl-CoA pathway
will be used to explore these mecha...

## Key facts

- **NIH application ID:** 10131792
- **Project number:** 5K01DK116922-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Rachel Raeburn Webster Stine
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $118,862
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10131792

## Citation

> US National Institutes of Health, RePORTER application 10131792, PRDM16 regulation of metabolism in the intestinal stem cell niche (5K01DK116922-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10131792. Licensed CC0.

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