# Mimicking, Exploiting, and Understanding Biology's Heterogeneity in 4D

> **NIH NIH R35** · UNIVERSITY OF WASHINGTON · 2020 · $371,605

## Abstract

PROJECT SUMMARY
Our bodies consist of an exquisite collection of tissues and organs that undergo constant change. From
morphogenesis and homeostasis to the progression of disease, these changes are associated with both the
healthy and unhealthy processes that define human life. My research program at the University of Washington
is developing robust and uniquely powerful multidisciplinary methodologies to mimic, exploit, and quantify
these changes, particularly as they evolve in both time and 3D space (i.e., 4D). In our lab’s first five years of
existence, we have: (1) developed a suite of synthetic cell-culture platforms whose biochemical and
biophysical properties can be reversibly modulated in 4D using cytocompatible photochemistries, and have
utilized these platforms to regulate proliferation, migration, differentiation, and intracellular signaling at single-
and sub-cellular resolutions; (2) introduced a photodegradable material-based approach to generate the first
endothelialized 3D vascular networks within cell-laden hydrogel biomaterials that span nearly all size scales of
native human vasculature (including capillaries); (3) reported the first modular framework for imparting
biomaterials with precise degradative responsiveness to multiple environmental cues/biomarkers following
user-programmable Boolean logic; and (4) established the first tools for “spatiotemporally resolved
proteomics”, enabling visualization and quantification of proteins produced in vitro and in vivo within user-
defined regions in 4D. The present proposal expands our group’s capabilities in each of these areas, paving
the way to new therapeutic targets and treatments of disease through a fundamentally transformed knowledge
of basic cell physiology. In this project, we will: (1) exploit our 4D-tunable biomaterials to recapitulate and probe
cardiovascular developmental signaling in vitro, examining the manner in which precise spatial and temporal
presentation of signaling proteins culminates in orchestrated differentiation; (2) employ synthetic capillaries to
examine drug action and resistance, screen therapeutics, and investigate microvascular occlusion, thrombosis,
and altered remodeling that occurs in many hematologic diseases (e.g., sickle cell anemia, spherocytosis); (3)
develop and deploy hydrogel nanoparticles exhibiting logic-based degradative response to cancer-presented
biomarkers to deliver small molecule chemotherapeutics to tumors with unprecedented specificity; and (4)
extend our 4D proteomic strategies to permit optically and physiologically defined proteomic mapping in living
tissue and model organisms. Critically, the methods that we are developing and implementing are cell-, tissue-,
and disease-agnostic, enabling enhanced understanding of a wide variety of biological processes while laying
the foundation for advances in disease diagnosis, treatment, and prevention.

## Key facts

- **NIH application ID:** 10028017
- **Project number:** 1R35GM138036-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Cole A DeForest
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $371,605
- **Award type:** 1
- **Project period:** 2020-09-15 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10028017

## Citation

> US National Institutes of Health, RePORTER application 10028017, Mimicking, Exploiting, and Understanding Biology's Heterogeneity in 4D (1R35GM138036-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10028017. Licensed CC0.

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