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Principal Investigator: Joelle Payne Straehla
Organization: DANA-FARBER CANCER INST
Fiscal Year: 2024
Award: $1
Funding agency: National Cancer Institute
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.
Terms: <14-Hydroxydaunomycin><Acceleration><Address><Adriamycine><Advisory Committees><Anabolism><Anti-Cancer Agents><Antineoplastic Agents><Antineoplastic Drugs><Antineoplastics><Area><Autoregulation><Award><Biologic Models><Biological Markers><Biological Models><Body Tissues><Boston><Campto><Cancer Drug><Cancer Patient><Cancer Treatment><Cancer cell line><Cancers><Cell Body><Cell Line><CellLine><Cells><Characteristics><Chemicals><Childhood><Childhood Cancers><Children's Hospital><Clinic><Clinical Trials><Clinical stratification><DF/HCC><Dana-Farber Cancer Institute><Data><Dependence><Doxorubicin><Doxorubicina><Drug Delivery><Drug Delivery Systems><Drugs><Education><Educational aspects><Engineering><Environment><Ether Phosphatidates><FDA approved><Fatty Acids><Formulation><Future><Genetic><Genotype><Glycerol Phosphate Ethers><Glycerophosphate Ethers><Goals><Homeostasis><Hydroxyl Daunorubicin><Hydroxyldaunorubicin><Image><Impairment><In Vitro><Injections><Intermediary Metabolism><International><Investigation><Investigators><Knock-out><Knockout><Knowledge><Leadership><Link><Lipids><Liposomal><Liposomes><Malignant Cell><Malignant Childhood Neoplasm><Malignant Childhood Tumor><Malignant Neoplasm Therapy><Malignant Neoplasm Treatment><Malignant Neoplasms><Malignant Pediatric Neoplasm><Malignant Pediatric Tumor><Malignant Tumor><Malignant childhood cancer><Massachusetts><Medication><Mentors><Mentorship><Metabolic Processes><Metabolism><Model System><Modeling><Molecular Transport><Nature><Neoplastic Disease Chemotherapeutic Agents><Neuroblastoma><Oncology><Oncology Cancer><Patients><Pediatric Hospitals><Pediatric Oncologist><Pediatric Oncology><Pharmaceutical Preparations><Phenotype><Phosphatides><Phospholipid Ethers><Phospholipid Metabolism><Phospholipids><Physicians><Physiological Homeostasis><Plasmalogens><Play><Position><Positioning Attribute><Research><Research Personnel><Researchers><Role><Scientist><Specificity><Starvation><Strains Cell Lines><Stratification><Structure><Systems Biology><Task Forces><Technology><Testing><Therapeutic><Tissues><Training><Translations><Transport Process><Treatment Efficacy><Tumor Cell><Tumor-Specific Treatment Agents><Work><advisory team><anti-cancer drug><anti-cancer research><anti-cancer therapy><bio-markers><biologic marker><biomarker><biosynthesis><camptosar><cancer biomarkers><cancer cell><cancer cell metabolism><cancer in a child><cancer in children><cancer markers><cancer metabolism><cancer research><cancer therapy><cancer-directed therapy><career><child with cancer><childhood malignancy><clinical biomarkers><clinically useful biomarkers><cultured cell line><design><designing><drug/agent><experience><fat metabolism><functional genomics><imaging><improved><in vivo><insight><interest><intervention efficacy><irinotecan><lipid based nanoparticle><lipid metabolism><lipid nanoparticle><liposomal delivery><liposomal formulation><liposomal preparation><liposome delivery><malignancy><nano><nano medicinal><nano medicine><nano particle><nano particle delivery><nano therapy><nano-sized particle><nanocarrier><nanomaterials><nanomedicinal><nanomedicine><nanoparticle><nanoparticle delivered><nanoparticle delivery><nanoparticle drug><nanoparticle therapy><nanosized particle><nanotherapeutic><nanotherapy><nanovessel><neoplasm/cancer><neoplastic cell><pediatric><pediatric cancer><pediatric malignancy><pre-clinical><preclinical><predictive biomarkers><predictive marker><predictive molecular biomarker><programs><response><skills><social role><solute><specific biomarkers><targeted agent><therapeutic efficacy><therapeutic nanoparticles><therapy efficacy><trafficking><translation><tumor><tumor cell metabolism><tumor metabolism><uptake>