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Research Specialist Support for Defining the Roles of Bone Marrow Adipocytes and FABP4/5 Signaling in Multiple Myeloma

Award Number: R50CA265331
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/12/2022
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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Research Specialist Support for Defining the Roles of Bone Marrow Adipocytes and FABP4/5 Signaling in Multiple Myeloma - Project Summary Cancer develops and ultimately flourishes due to both the nature of the tumor cells themselves as well as the microenvironment or ‘soil’ in which the tumor thrives. Multiple myeloma, a blood cancer that results from mutated plasma cells, grows in the rich soil of the bone marrow causing breakdown of the bone. The risk of developing myeloma is greater in older individuals and people with high body mass index who also typically have more bone marrow adipose tissue, or fat, than younger or leaner individuals. However, the relationship between bone marrow adipocytes (fat cells) and myeloma cells, as well as the specific mechanisms by which bone marrow adipocytes modulate myeloma disease progression are not well understood. Therefore, we aim to identify novel therapeutic avenues for the treatment of multiple myeloma patients by unlocking new vulnerabilities specific to the interactions between myeloma cells and bone marrow adipocytes, which can serve as a source of fatty acids and pro-myeloma cytokines. Our cell culture studies suggest bone marrow adipocytes induce drug resistance in myeloma cells- recapitulating a common problem for myeloma patients. We have found that one mechanism of cross-talk linking adipocytes with myeloma cells is through proteins called fatty acid-binding proteins 4 and 5 (FABP4 and FABP5). We will analyze how bone marrow adipocytes contribute to myeloma by using novel, three-dimensional (3D), tissue engineered cancer models which consist of bone marrow adipocytes and myeloma cells grown together on silk scaffolds. By growing myeloma cells in these 3D mini-bone environments, we can determine how myeloma cells change in response to adipocytes and discover new ways to target this interaction. We will also use our novel mouse models to study bone marrow adipocyte- myeloma crosstalk by increasing or removing bone marrow adipocytes in mice and quantifying effects on tumor growth and drug resistance. We will use these in vitro and in vivo models to specifically test the role of FABP4 and FABP5 in tumor progression and drug resistance, and work toward our long-term goal to better understand the molecules and mechanisms driving multiple myeloma growth in the bone marrow, and how cancer hijacks this niche for its own purposes. This proposal supports this endeavor by providing support for a Research Specialist to further develop, lead, and execute the experiments described which interrogate a novel part of the cellular “soil” (the bone marrow adipocyte), in which tumor cells, or “seeds” land and grow.


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 = $99,576 )
2025	2025	MAINEHEALTH	110 FREE ST	PORTLAND	ME	04101	CUMBERLAND	USA	Cancer Treatment Research	000	4	7/23/2025	NON-COMPETING CONTINUATION	$99,576
														Subtotal = $99,576

Issue Date FY: 2024 ( Subtotal = $99,576 )
2024	2024	MAINEHEALTH	110 FREE ST	PORTLAND	ME	04101	CUMBERLAND	USA	Cancer Treatment Research	000	3	6/20/2024	NON-COMPETING CONTINUATION	$99,576
														Subtotal = $99,576

Issue Date FY: 2023 ( Subtotal = $99,576 )
2023	2023	MAINEHEALTH	22 BRAMHALL ST	PORTLAND	ME	04102	CUMBERLAND	USA	Cancer Treatment Research	000	2	7/24/2023	NON-COMPETING CONTINUATION	$99,576
														Subtotal = $99,576

Issue Date FY: 2022 ( Subtotal = $99,576 )
2022	2022	MAINEHEALTH	22 BRAMHALL ST	PORTLAND	ME	04102	CUMBERLAND	USA	Cancer Treatment Research	000	1	8/12/2022	NEW	$99,576
														Subtotal = $99,576

Grand Total All Awards = $398,304

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Research Specialist Support for Defining the Roles of Bone Marrow Adipocytes and FABP4/5 Signaling in Multiple Myeloma

Award Number: R50CA265331

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/12/2022

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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