# Metabolic Control of Hair Follicle Stem Cell Homeostasis and Tumorigenesis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $470,519

## Abstract

Abstract
In the last five years, we discovered a functional role for glycolytic metabolism in HFSC
homeostasis. We found that lactate dehydrogenase (Ldh) activity is essential for HFSC activation,
and that elevation of Ldh activity through blockade of pyruvate entry into mitochondria can
promote HFSC activation. Left unknown from this work is why and how, specifically, HFSCs’
activation is subject to regulation by Ldh activity and/or pyruvate oxidation in the mitochondria.
HFSCs are essential for new hair growth, contribute to wound healing, and are cancer cells of
origin for squamous cell carcinoma. Therefore, understanding how metabolism can regulate cell
fate in HFSCs has important implications. We have several hypotheses to explain how Ldh activity
and/or mitochondrial pyruvate oxidation leads to HFSC activation. First, we have found that Ldh
inhibition in tumors promotes glutamine anapleurosis, and it has been argued that glutaminolysis
is important for HFSC maintenance, so perhaps elevated glutaminolysis prevents HFSC
activation in Ldh-null stem cells. Second, lactate has been shown to act as a signaling molecule,
sometimes referred to as a lactormone. Third, it is possible that instead of lactate, an alternate
product of Ldh activity, L-2-hydroxyglutarate (L2HG), is the key metabolite promoting HFSC
activation; L2HG can impact the activity of a diverse class of enzymes, some of which modulate
epigenetic state and gene expression. Fourth, we have evidence to suggest that these same
regulatory mechanisms are affecting the decision of HFSCs to initiate and drive tumorigenesis,
so we will explore these hypotheses in an established cancer paradigm for squamous cell
carcinoma.

## Key facts

- **NIH application ID:** 10882770
- **Project number:** 1R01AR084245-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Heather Christofk
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $470,519
- **Award type:** 1
- **Project period:** 2024-04-11 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10882770

## Citation

> US National Institutes of Health, RePORTER application 10882770, Metabolic Control of Hair Follicle Stem Cell Homeostasis and Tumorigenesis (1R01AR084245-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10882770. Licensed CC0.

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