# Development of a platform for spatial functional genomics

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $723,980

## Abstract

PROJECT SUMMARY
 There are >20,000 genes in the genome and though there has been progress in assigning many gene
functions, we still do not know the function of numerous genes or their specific roles in affecting disease. Genes
can direct diverse phenotypes in different cell types, cell states, or tissues, which makes gene annotation a
staggering task. Studies are needed to determine each gene’s function in different contexts, but the scope of the
problem is a challenge – it is necessary to assess many possible functions of 100s of genes and within the
context of a complex cellular and extracellular milieu whose spatial architecture is an essential component of
system behavior. In addition, some genes work coordinately or redundantly with other genes, making phenotypic
annotation more challenging. Establishing the role of every gene in different normal and disease states would
have an incalculable impact on biology and medicine. It would elicit novel intrinsic components of different
diseases and thus facilitate the development of drugs to treat some of these diseases.
 The objective of this project is to establish a first-of-its-kind platform for spatial functional genomics (Perturb-
map), which will enable 100s of genetic perturbations, including multi-gene knockouts, to be generated in parallel
in tissues and tumors, and the effect of each perturbation on multiple intrinsic and extrinsic biological processes
to be revealed at cellular, subcellular, and tissue level resolution. To reach our objective, we will develop novel
technologies, methods, and software tools that will permit 100s of CRISPRs, along with dozens of biological
phenotypes, to be spatially resolved within a tissue by high-dimensional imaging. To establish the potential of
Perturb-map to address urgent unmet needs, we will apply the platform to one of the most pressing questions in
immune oncology, namely how tumors prevent immune infiltration and subvert immunity. We will use Perturb-
map to identify factors that regulate immune recruitment and exclusion from the tumor microenvironment and
uncover genes controlling tumor resistance to immune clearance.
 The outcome of this project will be a transformative technology for functional genomics with spatial cellular
and sub-cellular resolution and high-dimensional phenotyping. This would have unmatched capabilities to
answer numerous questions in a broad array of biological areas, and to investigate entire classes of genes and
phenotypes that could not be studied with existing functional genomics approaches; enabling highly scaled
studies to identify genes that control processes such as: tissue and tumor organization, cell migration, invasion
and metastasis, cell-cell interactions, and local immune cell recruitment and crosstalk. By being able to
interrogate multiple gene perturbations within the same cell, Perturb-map will also enable genetic redundancies
and synthetic lethal relationships to be identified, a major area of interest...

## Key facts

- **NIH application ID:** 10031205
- **Project number:** 1R01AT011326-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Brian D Brown
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $723,980
- **Award type:** 1
- **Project period:** 2020-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10031205

## Citation

> US National Institutes of Health, RePORTER application 10031205, Development of a platform for spatial functional genomics (1R01AT011326-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10031205. Licensed CC0.

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