# Comprehensive Quantitative Profiling of Cellular Alterations Caused by Injury

> **NIH NIH R01** · UNIVERSITY OF HOUSTON · 2021 · $637,312

## Abstract

ABSTRACT
Currently, cellular alterations associated with pathological conditions are studied using low complexity
immunohistochemical (IHC) assays, typically utilizing 2-5 antibodies, that only reveal a tiny subset of the
alterations that are occurring, lack comprehensive cellular context, and do not provide quantitative readouts of
cellular changes throughout the tissue. For example, a injury or disease can initiate a complex web of
pathological alterations across cell types, and at multiple scales ranging from individual cells to multi-cellular
units and the layered brain cytoarchitecture. However, technological limitations are hindering a more
comprehensive global understanding of these pathological changes. This lack of understanding is hampering
our ability to intelligently design effective treatment regimens, and may have contributed to the failures of
clinical trials that targeted a single cell type or specific protein. To bridge this gap in our understanding, we
propose to develop a Comprehensive Brain Cellular Alteration Profiling Toolkit (CBAT), a carefully
validated and broadly applicable image analysis toolkit with unprecedented potential to accelerate investigation
& development of next-generation treatments for brain diseases. CBAT, in association with a flexible and
modular protocol for highly multiplexed IHC, will enable simultaneous profiling of all major brain cell types and
their functional/pathological status (e.g., resting, reactive, apoptotic) across whole brain sections. It will provide
quantitative readouts of cellular alterations at multiple scales ranging from individual cells of all types to multi-
cellular units (e.g. niches), brain cell layers, and brain regions. Comprehensive cellular profiling and
measurements generated using CBAT will enable a deeper understanding of pathological cellular changes that
will enable accelerated design, testing, and optimization of therapeutic interventions. Further, it will reduce
overall experimental costs by replacing a large number of less-informative assays with a single comprehensive
assay. In the longer term, it will enhance our ability to conduct the systems-level investigations that will be
required for fully understanding, and successfully treating, multiple brain pathologies. To achieve these goals,
we propose the following aims: Aim 1: Develop and validate a flexible, scalable, extensible, and reproducible
method for comprehensive whole slide imaging of all the major brain cell types in stereotactically aligned rat
whole brain sections; Aim 2: Develop and validate a turnkey software system profiling cell identify and status
at multiple scales ranging from individual cells to multi-cellular units, brain cell layers, and brain anatomic
regions; and Aim 3: Test the utility of the CBAT system to comprehensively profile concussion biology, and
assess the effectiveness of a drug combination to reduce newly identified pathologies. After its development
and validation, CBAT will be...

## Key facts

- **NIH application ID:** 10134453
- **Project number:** 5R01NS109118-03
- **Recipient organization:** UNIVERSITY OF HOUSTON
- **Principal Investigator:** PRAMOD K DASH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $637,312
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134453

## Citation

> US National Institutes of Health, RePORTER application 10134453, Comprehensive Quantitative Profiling of Cellular Alterations Caused by Injury (5R01NS109118-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10134453. Licensed CC0.

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