# Deciphering heritability, plasticity and differentiation trajectories in gliomas via single-cell multi-omics

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $546,900

## Abstract

Abstract
Cancer evolution constitutes a foremost obstacle to effective treatment, driving malignant cells to adapt
and overcome therapy. Diffuse glioma illustrates the quandary of cancer evolution: despite maximal
treatment, the disease invariably recurs. Recent single-cell RNA-sequencing (scRNAseq) profiling of
gliomas in the Suvà laboratory showed that defined cellular states, developmental hierarchies and
plasticity coordinate to fuel glioma growth, evolution and resistance to therapy. However, this raises the
critical question of the determinants of glioma cell states. We hypothesize that genetic, epigenetic
and micro-environmental determinants govern the biology of key cellular states that drive
gliomas and their plasticity, calling for an integrative model of cancer evolution, encompassing
all sources of intra-tumoral heritable variations. To address this challenge, the Landau laboratory
developed novel multi-modality single-cell sequencing technologies that enable direct integration
across genetic, epigenetic, and transcriptional dimensions of cell-to-cell variation, and have applied
them to study clonal evolution in hematological malignancies. In this R01 co-PI collaborative grant, we
seek to apply this multi-layered single-cell approach to human gliomas in order to define how cellular
phenotypic plasticity and clonal evolution enable tumor cell fitness. Specifically, we will: define intrinsic
and extrinsic determinants of cellular states in glioma (aim1), map the epigenetic encoding of
cell state programs in glioma (aim2), and reconstruct high-resolution lineage histories of glioma
single-cells to measure the heritability and plasticity of cell states (aim3). Altogether, this research
proposal seeks to pioneer the integrative analysis of epigenetic identity with genetic and transcriptional
information to systematically dissect drivers of cellular states that underlie glioma differentiation and
evolution.

## Key facts

- **NIH application ID:** 10383724
- **Project number:** 5R01CA258763-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Mario Luca Suva
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $546,900
- **Award type:** 5
- **Project period:** 2021-04-05 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10383724

## Citation

> US National Institutes of Health, RePORTER application 10383724, Deciphering heritability, plasticity and differentiation trajectories in gliomas via single-cell multi-omics (5R01CA258763-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10383724. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*