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Engineering Cellular Neighborhood Models of Bone Marrow Malignancies

Award Number: R61CA309704
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/19/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2029

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Engineering Cellular Neighborhood Models of Bone Marrow Malignancies - Project summary – This project will develop spatially engineered cellular neighborhoods for modeling malignant bone marrow niches from human biospecimens. Acute myeloid leukemia (AML) has a low 5-year survival rate of approximately 30% despite advancements in treatment options, including chemotherapy and immunotherapies. The late diagnosis of AML complicates understanding the biological origins and order of subsequent mutations. Recent single-cell studies reveal the complexity of the bone marrow microenvironment, highlighting the need for systems that can mimic neighborhoods of cells in bone marrow to improve ex vivo culture of leukemic cells. Developing new models for culturing patient cells ex vivo is essential to facilitate research and drug screening and study the microenvironment's influence on treatment responses. The technology plan will create hydrogel microgel assemblies to control the pairing of bone marrow cells. In Aim 1, we will engineer spatially distinct and programmable cellular neighborhoods of bone marrow niche cells. We will encapsulate cells in core-shell microgel beads, anneal beads together into micro-assemblies that mimic “neighborhoods,” encapsulate neighborhoods in hydrogels in a combinatorial manner, and selectively degrade the beads to release cells from their core-shell particles. The spatial control of cellular neighborhoods is based on input cellular composition, ratios, and total particle size. Programmable photo-click chemistry will provide programmable local mechanical and biochemical environments of individual neighborhoods. In Aim 2, we will model cellular neighborhoods of hematopoietic malignancies. First, we will evaluate whether we can achieve HSPC and MSC neighborhoods in vitro. We will use flow cytometry and multiplexed immunofluorescence labeling to generate a spatial analysis of the encapsulated cells. Next, we will develop a computational analysis of our model's orbital and nearest neighbor outputs. This quantitative approach will allow us to directly iterate and benchmark with previously published data from clinical samples. Next, we will encapsulate AML cells in these neighborhoods and evaluate AML cell proliferation. These studies will establish the feasibility of modeling the neighborhoods of HSPC and AML niches of bone marrow. Further studies in the R33 phase will develop the model parameters to mimic in vivo neighborhoods. The quantitative performance measures will focus on materials synthesis and characterization in Aim 1 and spatial analysis of cells in Aim 2. This system advances beyond traditional models by allowing precise investigations of cell-cell interactions of in vitro neighborhoods. This technology aims to enhance our investigation of patient biospecimens of bone marrow malignancies and ultimately improve patient care by aiding diagnostics and drug screening capabilities.


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 = $236,997 )
2026	2026	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Biology Research	000	1	8/19/2026	NEW	$236,997
														Subtotal = $236,997

Grand Total All Awards = $236,997

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Engineering Cellular Neighborhood Models of Bone Marrow Malignancies

Award Number: R61CA309704

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/19/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2029

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