# The epithelial matrisome and drug transport kinetics

> **NIH NIH R35** · OREGON STATE UNIVERSITY · 2024 · $352,205

## Abstract

PROJECT SUMMARY
The overarching goal of our research program is to couple computational tools with three-dimensional models
of epithelial barriers to interrogate how the epithelial extracellular matrix (ECM) is influenced by extrinsic factors,
how changes to the epithelial ECM affect drug delivery, and how the epithelial ECM can be harnessed to tailor
drug bioavailability. Epithelial barriers are what lies between us and the outside world, serving as protective
barriers and sites of selective permeability. For each type of epithelial tissue, each layer of stratified epithelium
has its own unique ECM, a complex network of fibrous proteins that provides mechanical and chemical cues that
drive cell proliferation, survival, differentiation, cell polarity, and migration. Dysregulation of epithelial barriers can
be indicative of local or systemic disease and permeability of epithelial barriers directly affects how drug is
delivered across the ECM and into the circulation. Recently, it has been appreciated that the ECM cannot be
fully studied as the fibrous proteins alone, but instead should be evaluated as the interconnected network of
proteins that make up the structural core of the ECM along with proteins that are critical to ECM function and
maintenance such as receptors and ECM-bound soluble factors. This interconnected network has been defined
as the matrisome, a curated collection of 1027 genes, roughly 4% of the known human proteome. While the
roles of individual ECM proteins and ECM downstream signaling networks on epithelial function and permeability
have been investigated, three key knowledge gaps persist: 1) How does the epithelial matrisome change with
extrinsic factors such as age, menstrual cycle, and inflammation? 2) How do changes to the epithelial matrisome
affect drug absorption and transport? 3) How can we modulate the epithelial matrisome for selective
bioavailability? To address the first knowledge gap, in Project 1 we will evaluate publicly available datasets and
biospecimens using our novel machine learning and image analysis techniques to reveal the interconnected
relationships between matrisome changes and extrinsic factors such as age, menstrual cycle phase, and
immune landscape. These studies will be complemented by orthogonal in vitro studies using our library of tissue
engineered models that capture the layered morphology of epithelium. To address the second knowledge gap,
in Project 2 we will couple our in vitro models with statistical modeling and systems biology tools to determine
key matrisome proteins that influence drug delivery across epithelial surfaces and their corresponding
mechanisms of action. Lastly, to address the third knowledge gap, in Project 3 we will identify novel compounds
that modulate bioavailability through matrisome-driven mechanisms, opening new avenues of direction for the
design and delivery of novel therapeutics with selective bioavailability. Critically, the methods that we are
developing are ...

## Key facts

- **NIH application ID:** 10893605
- **Project number:** 5R35GM151254-02
- **Recipient organization:** OREGON STATE UNIVERSITY
- **Principal Investigator:** Kaitlin C Fogg
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $352,205
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10893605

## Citation

> US National Institutes of Health, RePORTER application 10893605, The epithelial matrisome and drug transport kinetics (5R35GM151254-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10893605. Licensed CC0.

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