Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Single-molecule, Single-cell profiling of chromatin protein-protein interactions.

Award Number: DP2CA325383
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/10/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2031

Group Awards By:

View Award Description

Single-molecule, Single-cell profiling of chromatin protein-protein interactions. - PROJECT SUMMARY The immune system must balance the need to eliminate threats while avoiding damage to healthy tissues. Clinical trials in myelodysplastic syndromes (MDS) revealed that Polycomb proteins and DNA methylation establish epigenetic barriers that maintain this balance by limiting immune activation. Inhibition of these barriers can enhance anti-tumor immunity but may also trigger autoimmunity in certain contexts. Our overall goal is to build an epigenomics toolkit to identify gene-regulatory elements that distinguish “good” immune activation from “bad” immune activation. Specifically, I will define how epigenetic repression is altered in MDS and autoimmune disease, and whether the same programs that prevent autoimmunity also restrict anti-tumor responses. Existing methods cannot simultaneously measure Polycomb-mediated repression, DNA methylation, and the DNA-binding transcription factors that control the immune response, and this has limited our ability to resolve the mechanistic interactions of these epigenetic programs in primary human tissues. To address this, my lab is developing a novel strategy for simultaneous single-cell profiling of multiple chromatin proteins, while engineering Tn5 transposase variants for robust transcription factor mapping. Using joint profiling of histone modifications associated with transcriptional activation (H3K4me3) and Polycomb-mediated repression (H3K27me3), we have found that our approach can organize healthy immune cells along the trajectory from activation to exhaustion. We now propose to expand this toolkit by integrating transcription factor profiling with chromatin context and adding a single-molecule readout for DNA methylation at protein-bound sites. This will enable us, for the first time, to systematically characterize the series of epigenetic events underlying a balanced immune response. To test how epigenetic barriers shape immune activity, we will first examine whether ASXL1 mutations and hypomethylating agents prolong transcription factor binding at normal immune gene targets or enable binding at novel, normally silenced loci. We will then contrast these MDS-associated changes with autoimmune immune activation to determine whether beneficial, cancer-fighting responses can be distinguished from harmful, self-reactive ones at the molecular level. We expect these insights will inform more selective therapeutic strategies for cancer and autoimmunity. In addition, the epigenomics toolkit developed through this work will broadly enable mechanistic studies of gene regulation in complex human tissues in health and disease.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $912,000 )
2026	2026	VAN ANDEL RESEARCH INSTITUTE	333 BOSTWICK AVE NE	GRAND RAPIDS	MI	49503	KENT	USA	Trans-NIH Research Support	000	1	9/10/2026	NEW	$912,000
														Subtotal = $912,000

Grand Total All Awards = $912,000

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Single-molecule, Single-cell profiling of chromatin protein-protein interactions.

Award Number: DP2CA325383

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/10/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2031

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer