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Decoupling Bidirectional EphB/ephrinB2 in Multiple Myeloma

Award Number: K08CA245483
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 05/01/2021
PERIOD OF PERFORMANCE END DATE: 04/30/2025

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Decoupling Bidirectional EphB/ephrinB2 in Multiple Myeloma - Project Summary/Abstract My research objectives are to study the impact of decoupling the EphB4/ephrinB2 axis in multiple myeloma (MM), a cancer of antibody-secreting plasma cells, and the mechanisms through which outcomes of decoupling occur. The Eph/ephrin family is the largest family of receptor tyrosine kinases. Eph/ephrin interactions mediate bidirectional signaling events in juxtaposed cells. Our preliminary studies suggest that Eph/ephrin interactions between MM and bone marrow endothelial cells (BMECs) are required for MM pathogenesis. MM is the most common primary bone marrow malignancy and although recent advances in treatment have prolonged the life expectancy of patients suffering with this disease, it remains incurable and inexorably fatal. Understanding of the biology of MM will reveal vulnerabilities that will lead to the development of targeted therapies for malignant plasma cells. Additionally, our preliminary studies regarding Eph/ephrin signaling provide important new insights into the pathological reciprocity of cancer cells and their microenvironmental neighbors. Here, we will use new tools to decouple the partnership of the Eph receptor/ephrin interaction. Historically, separating influences of such signaling events was less feasible. Now armed with advanced tools, we propose to dissect the bidirectionality inherent in this signaling pathway and provide a new insight into the pathological basis of MM. My primary short-term goals are to combine my scientific research and clinical care into a medically relevant and scientifically rigorous endeavor, while expanding my scientific skillset and progressing toward an independent research program. This award, training plan, and scientific aims are a critical step in the merger of my clinical and research training. I plan to lead a laboratory program dedicated to furthering the understanding of hematopoietic cancer pathology and discovering new therapeutic avenues. Long-term, I plan to become a leader in hematopoietic malignancies and cellular therapy. My training outline, mentorship plan, and scientific strategy are constructed to best reach my goals. This plan builds on my strong foundation in hematopoietic stem cell biology to transition into cancer biology. The career development plan includes expanding my skillset to include 1) building relevant in vivo cancer models; 2) didactic and hands-on training in developing an expanded knowledge base, scientific research tools, and techniques relevant to cancer biology; 3) transition to independence, supported by the completion of the aims of this award. This proposed track has already been initiated and the strong preliminary results, I believe, predict a high likelihood of success.


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 = $0 )
2025	2024	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cancer Research Manpower	000	5	8/11/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $256,859 )
2024	2024	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cancer Research Manpower	000	5	4/11/2024	NON-COMPETING CONTINUATION	$256,859
														Subtotal = $256,859

Issue Date FY: 2023 ( Subtotal = $256,859 )
2023	2023	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cancer Research Manpower	000	4	4/25/2023	NON-COMPETING CONTINUATION	$256,859
														Subtotal = $256,859

Issue Date FY: 2022 ( Subtotal = $256,859 )
2022	2022	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Research Manpower	000	3	4/19/2022	NON-COMPETING CONTINUATION	$256,859
														Subtotal = $256,859

Issue Date FY: 2021 ( Subtotal = $256,859 )
2021	2021	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Research Manpower	001	2	8/3/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$256,859
2021	2021	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Research Manpower	003	2	8/13/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$149,045
2021	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Research Manpower	002	1	8/13/2021	NEW	-$149,045
2021	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Research Manpower	000	1	8/2/2021	NEW	$0
														Subtotal = $256,859

Issue Date FY: 2020 ( Subtotal = $257,099 )
2020	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Cancer Research Manpower	000	1	4/24/2020	NEW	$257,099
														Subtotal = $257,099

Grand Total All Awards = $1,284,535

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Decoupling Bidirectional EphB/ephrinB2 in Multiple Myeloma

Award Number: K08CA245483

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 05/01/2021

PERIOD OF PERFORMANCE END DATE: 04/30/2025

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