# The Roles of a Novel Microprotein in Wound Healing and Cancer

> **NIH NIH K01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2022 · $171,972

## Abstract

Project Summary
The pathways that regulate processes necessary for wound healing, such as proliferation and migration, are
often co-opted by tumors, leading to their description as wounds that do not heal. Therefore, identifying novel
genes involved in wound healing and understanding how they are dysregulated in cancer may provide new
targets for therapeutic efforts. We recently discovered thousands of small open reading frames that encode
proteins <100 amino acids, dubbed microproteins. Among these was a 10 kDa microprotein encoded on the
lncRNA Terminal Differentiation-Induced non-coding RNA (TINCR), which is a critical inducer of terminal
differentiation in the epidermis and regulator of cancer cell proliferation and migration. TINCR microprotein
(TINCR-MP) is highly conserved across mammals, strongly suggesting that it is functional. Compelling
preliminary data demonstrate that in human skin models TINCR-MP downregulates signaling pathways involved
in wound healing, and that it interacts with histone modifying enzymes that have functions in differentiation and
cancer. Furthermore, while TINCR-MP is expressed during epidermal differentiation, it is unnecessary for
differentiation, making its function separate from the differentiation promoting activity of TINCR RNA. The central
hypothesis is that TINCR-MP acts as a brake for proliferation and migration during wound healing through
alterations to the epigenetic landscape, and that this function is hijacked in cancer cells to promote tumor
progression. The goals of this proposal are thus: 1) to determine the role of TINCR-MP in cutaneous wound
repair processes, and establish whether TINCR-MP effects on wound healing are driven by epigenetic
modifications, 2) to determine the extent to which TINCR-MP regulates proliferation and migration in prostate
and breast cancer cell lines, and establish its effects on epigenetic and subsequent gene expression changes,
and 3) to identify additional microproteins regulated during differentiation that affect cancer proliferation.
Successful completion of these aims will reveal an important microprotein that functions in wound healing and
tumor progression, as well as new microproteins to investigate. The candidate, Dr. Thomas Martinez, plans to
develop an independent research program focused on characterizing microproteins that function in both
differentiation and cancer. The opportunities offered by this Career Development Award will allow Dr. Martinez
to deepen his knowledge of developmental biology, epigenetics, and cancer biology. He will also gain experience
utilizing 3D ex vivo skin models, in vivo mouse models, and techniques for analyzing the epigenetic landscape.
Dr. Martinez will conduct these studies under the mentorship of Dr. Alan Saghatelian, expert on peptide biology,
as well as co-mentors Dr. Diana Hargreaves and Dr. George Sen, experts on chromatin remodeling complexes
in disease and epidermal homeostasis, respectively. Dr. Martinez’s Advisory...

## Key facts

- **NIH application ID:** 10476274
- **Project number:** 5K01CA249038-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Thomas Farid Martinez
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $171,972
- **Award type:** 5
- **Project period:** 2021-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10476274

## Citation

> US National Institutes of Health, RePORTER application 10476274, The Roles of a Novel Microprotein in Wound Healing and Cancer (5K01CA249038-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10476274. Licensed CC0.

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