# Core 1: Cellular diagnostics/imaging core

> **NIH NIH P01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $358,575

## Abstract

The mission of the cellular diagnostics/imaging core is two fold. First, we will provide state-of-the art imaging
technology and cell analysis tools to meet the scientific needs of the four projects in this PPG. We will work
closely with project investigators to perform quantitative measurements and data analysis, customizing
instrumentation and optimizing experimental protocols as necessary. Second, we will pursue new technical
innovations that will lead to future scientific advances beyond what can be accomplished with existing
technologies. The Core is a unique resource with deep expertise in optical technology, intravital microscopy,
instrumentation design and fabrication, as well as image processing and data analysis. We also have a
record of productive collaborations with multiple investigators in this PPG, including Dr. Scadden (Project 1),
Dr. Nahrendorf (Project 2), and Dr. Swirski (Project 3). Our laboratories are all physically co-located in the
same building, making the Core a common meeting place where team members from various laboratories
converge, not just to use the facility but also to interact and exchange ideas. To carry out the mission of the
Core, we propose the following Specific Aims. In Aim 1, we will work with Projects 1 and 4 to perform clonal
analysis of hematopoietic cells based on their expression of multi-color fluorescent proteins. We will expand
the multi-color capability of our in vivo flow cytometer, a technology developed in our laboratory for real-time
detection and quantification of fluorescent cells in the circulation of live animals without the need to draw
blood samples, to enable noninvasive monitoring of the clonal dynamics in the peripheral circulating
leukocyte population. In Aim 2, we will work with Project 2 to assess how the bone marrow (BM) vasculature
is altered by cardiovascular diseases (CVD). We will measure functional parameters such as blood flow,
vascular permeability, vascular reactivity, and trans-endothelial migration, by performing multiphoton
imaging of the BM vasculature together with second-harmonic imaging of the extracellular matrix
component. We will also work with Project 3 to characterize hematopoietic stem cell (HSC) localization and
dynamics in the BM in the settings of MI and atherosclerosis using gene-edited HSCs provided by the
Genome Engineering Core. In Aim 3 we propose to develop a new method to enable image-guided laser
microdissection and extraction of live cells from the BM for single cell molecular profiling. We will initially
focus on capturing BM vascular endothelial cells, as they form a critical component of the HSC niche and
also regulate leukocyte trafficking and macromolecular transport. The technique will bridge the existing
divide between single-cell analysis on the one hand, which provides molecular but no spatial information,
and live imaging on the other, which supplies the 3D spatial context lacking in the molecular analysis. The
technique can be extended...

## Key facts

- **NIH application ID:** 10469358
- **Project number:** 5P01HL142494-04
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Charles P. Lin
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $358,575
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10469358

## Citation

> US National Institutes of Health, RePORTER application 10469358, Core 1: Cellular diagnostics/imaging core (5P01HL142494-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10469358. Licensed CC0.

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