# Multicomponent Therapy for Age-related Skin Stem Cell Deficiency

> **NIH NIH P01** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $2,351,620

## Abstract

SUMMARY
Chronic ulcers, defined as wounds that fail to heal within a three-month period, are associated with age-related
dysfunction in skin stem cells that not only has potential to blunt tissue repair, but also accounts for skin fragility,
atrophy, and the "aging phenotype" that itself has clinical as well as psychosocial implications. Non-healing
ulcers in aging individuals represent a multibillion dollar burden in the United States and to society globally, both
through utilization of health care resources as well as through reduction in productivity. Nonetheless, it is
recognized that "the basic biology and the influence of age-associated changes on wound healing are poorly
understood, and there are numerous research questions still to be answered". To address this important issue,
we have 1) assembled a highly collaborative and multidisciplinary team of investigators with established track
records in skin pathology, regenerative and stem cell biology, wound healing, bioinformatics, and the
pathobiology of aging; 2) leveraged the resources of seven Harvard Institutions to develop a unified and state-
of-the-art approach to decipher the role skin stem cell deficiency in age-related defective wound healing; and 3)
generated data-based hypotheses and identified inter-project synergies that will maximize productivity and
translational focus. Our fundamental hypothesis is that identification and interrogation of three major, inter-
related, and therapeutically targetable/reprogrammable pathways relevant to age-related skin stem cell
dysfunction, a) metabolic, b) epigenetic, and c) membrane transporter/receptor, will pave the way for
combinatorial (multicomponent) therapies necessary for more robust healing and regenerative responses to skin
injury. We will pursue this goal through six strategies that have been developed by the key personnel of this
PPG: 1) discovery of biomarkers for epidermal and dermal stem cell identification and manipulation; 2)
determination of metabolic regulators required for epidermal progenitor activity and maintenance; 3) identification
of novel epigenetic pathways that govern skin stem cell function and vitality; 4) development and evaluation of
unique murine models that permit study of human wound healing in vivo; 5) deployment of lineage tracking
technologies that facilitate detection of experimentally-manipulated stem cell fate in healing wounds; and 6)
generation of new animal strains and for epigenomic induction of premature aging and methods for genomic
restoration of stem cell youth and pluripotency. Our overall aims seek to answer the following questions: 1) How
can one map the key metabolomic, epigenetic, and cell receptor stem cell pathways that drive age-related wound
healing dysfunction?; 2) What are the therapeutically-accessible nodes for stem cell-directed multicomponent
combinatorial targeting within these pathways?; and 3) What are the agents that likely will affect restoration of
robust and regenerativ...

## Key facts

- **NIH application ID:** 10494654
- **Project number:** 1P01AG071463-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Markus H. Frank
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,351,620
- **Award type:** 1
- **Project period:** 2022-09-30 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10494654

## Citation

> US National Institutes of Health, RePORTER application 10494654, Multicomponent Therapy for Age-related Skin Stem Cell Deficiency (1P01AG071463-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10494654. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*