Wednesday, August 20, 2025 8/20/2025

Defining and targeting the lung cancer progenitor cell niche using a high-resolution, multi-omics approach

Award Number: F30CA265288
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/07/2021
PERIOD OF PERFORMANCE END DATE: 09/07/2026

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Defining and targeting the lung cancer progenitor cell niche using a high-resolution, multi-omics approach - Project Summary Despite advances in treatment options, 5-year overall survival (OS) for non-small cell lung cancer (NSCLC) patients remains around 20% [1]. Subpopulations of tumor initiating cells (TICs) representing <1.5% of the overall tumor population exhibit the capacity for self-renewal, drug-resistance, and are believed to drive disease progression [2]. Although surface markers including CD133, CD44, CD166, and EPCAM have been proposed to isolate lung TICs, results are inconsistent. Micro-heterogeneity within the tumor microenvironment (TME) is believed to regulate balance between progenitor-like and differentiated tumor cell phenotypes, and consequently supports heterogeneous drug responses. This proposed research attempts to definitively characterize expression profiles of TICs, and study the relationship between the tumor micro-environment and TIC dynamics in the context of drug response, with the goal of identifying critical pathways that mediate transitions to a progenitor-like state. Aim 1 - Lineage tracing studies suggest that TICs exhibit clonal dominance in culture, whereby a small fraction of tumor cells tend to drive outgrowth of the overall population. Having already established a protocol using cell line models, I will transfect patient-derived NSCLC cells with RNA-expressed barcodes and analyze growing populations using serial passaging assays under normal and drug-treated conditions. Using transcriptional analysis of time-series single-cell RNA Sequencing (scRNA-Seq) data in combination with custom computational tools, I aim to identify gene expression profiles and surface markers unique to progenitor-like subclones that drive population growth under treatment selection pressure. Aim 2 - TICs are dependent on niche signalling from a heterogeneous tumor microenvironment (TME) to support the progenitor phenotype. We hypothesize that micro-heterogeneity within the TME regulates the ratio of progenitor-to-differentiated tumor cells and influences drug sensitivity. I will first develop an in-vitro spheroid culture platform combining clonally barcoded patient-derived tumor and stromal cells exposed to cytotoxic therapy, processing them with the 10X Genomics Spatial Transcriptomics platform. This data will enable assessment of essential TME crosstalk signalling and its impact on spatial cancer projenitor-like transcriptional signatures defined from Aim 1. We will confirm these insights by integrating scRNA-Seq and Spatial Transcriptomics data from naive and post-treatment patient-derived lung samples used for Aim 1 to characterize patient-specific TIC niches. Through the robust profiling of the TIC transcriptional profile and its associated microenvironment using multimodal sequencing approaches, we hope to potentially identify new targets or prognostic biomarkers to aid in the treatment of NSCLC.


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: 2025 ( Subtotal = $54,538 )
2025	2025	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Cancer Research Manpower	001	4	8/15/2025	NON-COMPETING CONTINUATION	$54,538
2025	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Cancer Research Manpower	000	3	3/19/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $54,538

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Cancer Research Manpower	000	3	9/3/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $52,694 )
2023	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Cancer Research Manpower	000	3	8/22/2023	NON-COMPETING CONTINUATION	$52,694
														Subtotal = $52,694

Issue Date FY: 2022 ( Subtotal = $45,152 )
2022	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Cancer Research Manpower	000	2	8/8/2022	NON-COMPETING CONTINUATION	$45,152
														Subtotal = $45,152

Issue Date FY: 2021 ( Subtotal = $45,636 )
2021	2021	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Cancer Research Manpower	001	1	7/12/2021	NEW	$0
2021	2021	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Cancer Research Manpower	000	1	7/12/2021	NEW	$45,636
														Subtotal = $45,636

Grand Total All Awards = $198,020

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Defining and targeting the lung cancer progenitor cell niche using a high-resolution, multi-omics approach

Award Number: F30CA265288

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/07/2021

PERIOD OF PERFORMANCE END DATE: 09/07/2026

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