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Investigating SLC46A3 as a negative regulator of nanoparticle drug delivery

Award Number: K08CA277014
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 07/05/2024
PERIOD OF PERFORMANCE END DATE: 08/31/2029

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Investigating SLC46A3 as a negative regulator of nanoparticle drug delivery - PROJECT SUMMARY Nanoparticle-based therapies have many potential advantages for treating cancer, but there are currently no clinical biomarkers to predict which patients are most likely to benefit from nanotherapeutics over conventional anticancer agents. To improve the efficacy of nanoparticles for cancer treatment, I will investigate nanoparticle drug delivery in the context of SLC46A3, a liposome-specific biomarker recently identified in a massively parallel pooled cancer cell line screen. Based on strong preliminary data, I hypothesize that SLC46A3 plays a role in phospholipid metabolism in cancer cells, making it a therapeutically relevant biomarker for liposomal nanotherapeutics. This proposal aims to establish the role of SLC46A3 in phospholipid homeostasis and directly connect SLC46A3 expression to therapeutic liposome delivery in vivo using pediatric neuroblastoma as a model system. The ultimate goal of the project is to validate SLC46A3 as a clinical biomarker for liposomal nanoparticle delivery and develop rigorous preclinical data to motivate biomarker-stratified clinical trials for both existing, FDA- approved liposomes and experimental formulations. I am a pediatric oncologist seeking K08 support for a mentored training period under the co-mentorship of Dr. Paula Hammond at the Massachusetts Institute of Technology (MIT) and Dr. Kimberly Stegmaier at Dana-Farber Cancer Institute/Boston Children’s Hospital (DFCI/BCH). My long-term career goal is to be an independent physician-scientist, studying nano-bio interfaces and interactions with the goal of advancing nanomedicine to the clinic for cancer patients. My prior research experiences have established my skills in nanomedicine and drug delivery. I am now well positioned to establish the necessary expertise in cancer metabolism and functional genomics through the critical mentored K08 award. The DFCI/BCH, MIT and the Broad Institute of MIT and Harvard are internationally recognized research programs with a number of expert researchers in the areas of functional genomics, metabolism and nanomaterials, among others. The DFCI Division of Pediatric Oncology has a distinguished record of training young physician-scientists for leadership roles in pediatric cancer research. I have assembled an excellent mentoring and advisory committee, consisting of Dr. Matthew Vander Heiden (MIT), Dr. Angela Koehler (MIT), and Dr. Steven Dubois (DFCI), who will guide my research and training experiences along with my mentors. With structured mentoring, educational, and scientific plans, I will acquire the necessary expertise to become a successful independent investigator in translational cancer nanomedicine.


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 = $230,947 )
2026	2026	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	Cancer Research Manpower	000	4	7/14/2026	NON-COMPETING CONTINUATION	$230,947
														Subtotal = $230,947

Issue Date FY: 2025 ( Subtotal = $230,947 )
2025	2025	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	Cancer Research Manpower	003	3	8/22/2025	NON-COMPETING CONTINUATION	$230,947
2025	2024	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Research Manpower	002	1	6/12/2025	NEW	$0
2025	2024	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Research Manpower	000	1	5/7/2025	NEW	-$230,946
2025	2024	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	Cancer Research Manpower	001	2	5/7/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$230,946
														Subtotal = $230,947

Issue Date FY: 2024 ( Subtotal = $230,947 )
2024	2024	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Research Manpower	000	1	7/5/2024	NEW	$230,947
														Subtotal = $230,947

Grand Total All Awards = $692,841

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Investigating SLC46A3 as a negative regulator of nanoparticle drug delivery

Award Number: K08CA277014

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 07/05/2024

PERIOD OF PERFORMANCE END DATE: 08/31/2029

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