# Elucidating Mechanisms for Rapid Vascularization by Modeling Vascular Islands in Early Embryogenesis

> **NIH NIH F31** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2022 · $49,252

## Abstract

Project Summary/Abstract
Mechanisms of capillary plexus formation have been well studied in avian, zebrafish, and mammalian embryos,
with the precise timing of these processes being found to have profound importance in the formation of an
efficient and robust vasculature. However, due to the limitations of in vivo developmental models, no results of
modifying initial conditions or temporally modifying the initiation of flow and the importance of increased viscosity
when blood cells enter circulation are unknown. Recent reports have leveraged the precise control available
within microfluidic in vitro devices to elucidate novel angiogenic mechanisms. The objective of this proposed
research is to determine how temporally modulating the shear stress, media viscosity, and increasing cortical
actin assembly through a non-canonical Notch pathway affect the transition of a nascent capillary bed into an
aligned quiescent vascular network, and determine the molecular cues that cause a transition from a stable
quiescent network to a highly dynamic phenotype. Experiments will be carried out in an in vitro dual-channel
microfluidic device to precisely control experimental conditions that are unavailable in in vivo models. The overall
hypothesis of this proposal is that changes in shear force and fluid viscosity initiated immediately after
formation of the primitive plexus, enable rapid and efficient vascular remodeling, which is stabilized by
a cortical reinforcing non-canonical Notch pathway. We will address this hypothesis and achieve the
proposed goals by first determining how precisely timed shear force, dynamic viscosity changes, and addition of
exogenous protein expression on nascent vasculature affects cortical reinforcement, network dynamics, and
morphology. Secondly, we will elucidate the main molecular and mechanotransduction mediated role of cortical-
Notch signaling in network adaptation to altered flow profiles. The ramifications of altered force applied to
vascular islands and a nascent vasculature and how it allows vascular network remodeling will be determined,
and ascertain whether inhibition of parts of the cortical-Notch pathway allows the network to revert from being
stably quiescent to highly dynamic and proliferative without compromising the overall expression of canonical-
Notch expression. More complete understanding of this process is of significant biological and clinical importance
as it will allow novel restorative therapies for highly prevalent and deadly vascular diseases such as Peripheral
Arterial Disease (PAD) and Ischemic Heart Disease (IHD).

## Key facts

- **NIH application ID:** 10492476
- **Project number:** 5F31HL156517-02
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Alex Lammers
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $49,252
- **Award type:** 5
- **Project period:** 2021-09-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10492476

## Citation

> US National Institutes of Health, RePORTER application 10492476, Elucidating Mechanisms for Rapid Vascularization by Modeling Vascular Islands in Early Embryogenesis (5F31HL156517-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10492476. Licensed CC0.

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