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OutSmarting Osteosarcoma 2025 Recipients

OUTSMARTING OSTEOSARCOMA AWARDS 2025

OutSmarting Osteosarcoma 2025 Hero Grants

Alexander Davies, DVM. PhD | Oregon Health & Science University Knight Cancer 

Validation of MCL1 inhibition and combinatorial therapy for elimination of osteosarcoma lung metastasis

Granted in partnership with Fishin' for the Cure, Because of Matthew

For Abstract

OutSmarting Osteosarcoma 2025 Hero Grants

Study Summary

This study will evaluate the effectiveness of the next-generation MCL1 inhibitor zamzetoclax, both alone and in combination with the FGFR inhibitor pazopanib, in targeting osteosarcoma lung metastases. They will compare the potency of zamzetoclax to a previous MCL1 inhibitor, AZD5991, using osteosarcoma cell lines and mouse models. The research will also include preclinical testing of the combination therapy’s ability to eliminate metastatic tumors and an assessment of its safety profile.

About the Principal Investigator

Dr. Alexander Davies graduated with a Ph.D. in Biochemistry and Molecular Biology and a D.V.M., with an interest in comparative oncology, from the University of California, Davis. He then completed a post-doctoral fellowship in cancer biology at Lawrence Berkeley National Laboratory before joining The Ohio State University as faculty in the Department of Veterinary Biosciences. While at OSU, he was a member of the Comprehensive Cancer Center and faculty in the Cancer Biology and Cancer Engineering programs. Currently, Dr. Davies is an Assistant Professor at the Knight Cancer Institute within the Division of Oncological Sciences and Cancer Early Detection Advanced Research Center (CEDAR), with a joint appointment in the Department of Pediatrics. His work focuses on dynamic tumor-microenvironment signaling cross-talk, signal integration, and the development of 3D organotypic and tissue models to study these interactions using advanced live-cell microscopy techniques.

Amy LeBlanc, DVM | National Cancer Institute

A comparative approach to exploring fluorescence in situ hybridisation (FISH) biomarkers for advancing the diagnosis, prognostication and treatment of osteosarcoma

For Abstract

OutSmarting Osteosarcoma 2025 Hero Grants

Study Summary

The data generated in this proposal will greatly facilitate stratification of canine OS patients for future clinical trials, with the intent to directly inform human trials. We will also be positioned to identify links between CNV signatures and prognosis, which has strong potential for clinical translation in both species.

About the Principal Investigator

Dr. Amy LeBlanc is a board-certified veterinary oncologist, Senior Scientist, and the Director of the intramural NCI’s Comparative Oncology Program. In this position, she conducts preclinical mouse and translational pet dog studies that are designed to inform the drug and imaging agent development path for human cancer patients, specifically those with osteosarcoma. She directly oversees the NCI Comparative Oncology Trials Consortium (COTC), which provides the infrastructure necessary to connect participating veterinary academic institutions with stakeholders in drug development to execute fit-for-purpose comparative clinical trials in novel therapeutics and imaging agents. Her program provides support to several extramural NCI-funded initiatives, including the Integrated Canine Data Commons and Cancer Moonshot-funded canine immunotherapeutic clinical trials conducted under the PRECINCT network.

Corey Weistuch, PhD | Memorial Sloan Kettering Cancer Center

Implementing personalized, adaptive therapies in osteosarcoma

For Abstract

OutSmarting Osteosarcoma 2025 Hero Grants

Study Summary

This project aims to validate targeted drug candidates for osteosarcoma (OS) using patient-derived xenograft (PDX) models, leveraging a newly developed atlas of OS transcriptional states to guide personalized, adaptive treatment strategies. By testing archetype-specific therapies in different disease phases, the study seeks to establish a foundation for precision-based clinical trials, ultimately improving outcomes for patients with advanced or refractory OS.

About the Principal Investigator

Corey Weistuch, PhD, is an Assistant Attending Physicist in the Service for Predictive Informatics within the Department of Medical Physics at Memorial Sloan Kettering Cancer Center. His work is focused on developing mathematical models to understand cancer development, progression, and metastasis by integrating multimodal data. Central to this approach is the recognition that tumors occupy a finite spectrum of functional states, each characterized by distinct treatment sensitivities and metastatic tendencies that evolve over time and in response to therapy. His research centers on two primary objectives: 1) developing innovative mathematical tools to identify cancer phenotype drivers, and 2) precision modeling of cancer evolution and site-specific metastatic dissemination. By leveraging his interdisciplinary training in mathematics and biology, he collaborates closely with experimental biologists and clinicians to ensure that his computational predictions are effectively translated into tangible clinical applications and trials.

David Ulmert, MD, PhD | University of California, Los Angeles

High-throughput characterization of pathobiological responses in osteosarcoma tumors treated with LRRC15-targeted radiotherapy to uncover curative co-treatment approaches

Granted Because of Sydney

For Abstract

OutSmarting Osteosarcoma 2025 Hero Grants

Study Summary

This project aims to elucidate osteosarcoma responses to LRRC15-targeted radiotherapy, slated for patient translation this year. Through high-throughput technologies, we will identify biomarkers, prediction models, and transcriptional regulators of the TGFß-LRRC15 axis. By examining radiopathobiological changes and immune reprogramming, we will define druggable events to guide co-treatment strategies, driving near-term impacts on patient studies and therapeutic advancements.

About the Principal Investigator

Dr. David Ulmert is an expert in oncology and biotechnology, specializing in cancer biomarkers and targeted therapies. His research focuses on antigens secreted by luminal tissues as novel cancer-specific targets and circulating biomarkers. He developed high-affinity antibodies against androgen receptor-regulated enzymes hK2 and PSA, now in clinical trials across the US, Europe, and Australia—in collaboration with Janssen—for radioimmunotheranostics, CAR-T therapy, and bispecific targeting. His lab also developed DUNP19, an LRRC15-targeting antibody licensed to Lantheus, with a Phase 1 trial in osteosarcoma planned for 2025. Dr. Ulmert leads UCLA’s Preclinical Theranostics Program and conducts population-based studies on cancer biomarkers and risk factors with international collaborators. He is widely recognized for advancing prostate cancer research and translational immunotheranostics.

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OutSmarting Osteosarcoma 2025 Hope YI Grants

Aafrin M. Pettiwala, PhD | University of California, San Francisco

Identifying mechanisms of chemoresistance in metastatic osteosarcoma using molecular barcoding

For Abstract

OutSmarting Osteosarcoma 2025 Hope YI Grants

Study Summary

This study aims to investigate how intratumoral heterogeneity drives chemoresistance and metastasis in osteosarcoma by using lineage tracing (CaTCH) and patient-derived xenograft models. By identifying resistant and metastatic cell subpopulations and their molecular vulnerabilities, the research seeks to uncover new therapeutic targets to improve treatment outcomes for metastatic osteosarcoma patients.

About the principal Investigator

Aafrin earned her PhD in Cancer Biology from Institut Curie in Paris, France, where she studied therapeutic resistance and phenotypic plasticity in brain tumors. Her doctoral work focused on uncovering the molecular mechanisms that allow cancer cells to adapt and evade treatment. Currently, Aafrin is a postdoctoral researcher in the lab of Dr. Alejandro Sweet-Cordero at the University of California, San Francisco (UCSF). Her research centers on understanding chemotherapy resistance in metastatic osteosarcoma, with an emphasis on clonal dynamics, tumor evolution, and lineage tracing using high-throughput barcoding technologies.

Ali Cihan, PhD | Memorial Sloan Kettering Cancer Center

Targeting EPHA2 with dual-armored CAR T cells for immunotherapy in pediatric osteosarcoma

Granted Because of Isaac

For Abstract

OutSmarting Osteosarcoma 2025 Hope YI Grants

Study Summary

This study will provide additional preclinical data to support clinical translation of a novel EPHA2-targeting CAR T cell therapy for osteosarcoma (OS) patients. By integrating IL-18 and our novel LIGHT armors, we aim to enhance CAR T cell persistence and efficacy. The proposed work will directly support the development of an investigator-led clinical trial for pediatric patients with metastatic or relapsed OS within 2 years and addresses an ongoing need for therapeutic options in high-risk OS.

About the principal Investigator

Dr. Ali Cihan is a research scholar at Memorial Sloan Kettering Cancer Center, where he focuses on immunotherapy with a particular emphasis on advancing cellular therapies for pediatric solid tumors, including osteosarcoma. He received his Ph.D. from The Rockefeller University, where his research explored how chromosomal abnormalities and transcriptional dysregulation contribute to the development of high-risk pediatric leukemias. Motivated by the urgent need to improve outcomes for children with cancer, especially those facing limited treatment options, Dr. Cihan turned his focus to bridging laboratory discoveries and clinical application. His current work aims to develop immune-based therapeutic strategies that address the unique biological and clinical challenges of pediatric cancers.

Andrew S. Clugston, PhD | University of California, San Francisco

Oncogenic structural variation in the genome of pediatric osteosarcoma

Granted in partnership with the RISE Foundation, Because of Reese

For Abstract

OutSmarting Osteosarcoma 2025 Hope YI Grants

Study Summary

This study aims to identify key oncogenic driver genes in osteosarcoma by mapping structural variations (SVs) and their effects on gene expression and genome organization using optical genome mapping (OGM) and chromatin conformation capture (HiC). By integrating these data with whole-genome and RNA sequencing, the research seeks to uncover tumor-specific therapeutic targets and design precision treatments for osteosarcoma.

About the principal Investigator

Andrew Clugston grew up in the small town of Lake Luzerne, New York. He received a BS in Biochemistry and an MS in Chemistry at the Rochester Institute of Technology, and he received his PhD in Integrative Systems Biology at the University of Pittsburgh. During his PhD he learned to use and develop bioinformatics tools and techniques to study the role of the genome in kidney as well as eye development, and in the process became fascinated with the importance of 3-dimensional organization in regulating cell behavior. Andrew has since joined the Sweet-Cordero laboratory in the Pediatric Oncology Division at the University of California San Francisco as a Postdoctoral Fellow. There, he applies his knowledge and skillset to study how disruptions in these organizational principles allow osteosarcoma cells to develop and proliferate, and how these changes reveal tumor-specific vulnerabilities that can be exploited for fast and effective treatment options that improve the lives of patients.

Janeala Morsby, PhD | St. Jude Children's Research Hospital

Synergy of ATM and PARP inhibitors in pediatric osteosarcoma

Granted Because of Buddy

For Abstract

OutSmarting Osteosarcoma 2025 Hope YI Grants

Study Summary

This study aims to explore a novel combination therapy for osteosarcoma by targeting the DNA damage response pathway through dual inhibition of ATM and PARP. Using CRISPR-Cas9 screening, in vitro validation, and in vivo testing in patient-derived models, the research seeks to uncover the mechanism of synergy between these inhibitors and evaluate their potential for clinical translation in pediatric osteosarcoma.

About the principal Investigator

Janeala Morsby hails from the beautiful island of Jamaica, where she was born and raised in Port Antonio, Portland. Her journey to the United States began when she received a full honors scholarship to attend Claflin University, where she completed her Bachelor of Science in Biochemistry, summa cum laude. She then went on to complete her PhD at the University of Notre Dame under the supervision of Dr. Bradley Smith. At the University of Notre Dame, her work focused on the detection of hypoxia in cancer cell models, in addition to diagnostics and imaging. She is now a postdoctoral associate at St. Jude Children’s Research Hospital (SJCRH) in Dr. Lillian Guenther’s lab. At SJCRH, her work focuses on exploring the mechanism of synergy of the dual inhibition of ATM and PARP for the treatment of pediatric osteosarcoma. She is very passionate about the proposed research project and hopes that the findings of the proposed work will be beneficial to pediatric osteosarcoma patients.

Joseph Skeate, PhD | University of Minnesota

Next generation dual-CAR gamma delta T cells for the treatment of pediatric osteosarcoma

Granted Because of Annaleigh

For Abstract

OutSmarting Osteosarcoma 2025 Hope YI Grants

Study Summary

Gamma delta (yd) T cells can be used as an off-the-shelf therapy option to treat OSA. In this proposal, we will utilize our established engineering pipeline to create next-generation, cytokine-armored yd CAR-T cells that target two well-established OSA tumor antigens and function in OSA microenvironments. We will use this funding for future grant applications and start an Investigational New Drug (IND) application that we will translate into clinical studies within 3-5 years of this grant support

About the principal Investigator

As an Assistant Professor at the University of Minnesota, Dr. Joseph Skeate's primary research goal is to develop innovative cellular therapies for rare pediatric cancers through cross-disciplinary collaborations and to train the next generation of scientists in genome engineering. His previous research experience at the University of Southern California Keck School of Medicine Norris Comprehensive Cancer Center focused on basic and translational science in cervical cancer. Following the completion of his PhD in 2020, Dr. Skeate completed postdoctoral training at the University of Minnesota, gaining expertise in developing and applying transposon and Cas9 genome engineering technologies in primary immune cells. This specialization enabled him to establish effective engineering and testing pipelines, demonstrating in vitro and in vivo efficacy in multiple cancer models. Now, Dr. Skeate is dedicated to leveraging these advanced skills to develop and implement impactful cell therapies for pediatric diseases, especially in the areas of rare and poor-prognosis cancers.

Ram Rao, MD, PhD | Seattle Children’s Research Institute

Extracellular Matrix Degradation to Overcome Osteosarcoma Chemoresistance

For Abstract

OutSmarting Osteosarcoma 2025 Hope YI Grants

Study Summary

This study aims to investigate how the extracellular matrix (ECM) influences osteosarcoma chemoresistance and whether ECM-targeting strategies can enhance chemotherapy effectiveness. Using engineered 3D tumor models and a novel lung metastatic model, the research will assess how ECM density and stiffness impact drug response and explore the potential of relaxin (RLX) to degrade the ECM, reduce fibrosis, and improve treatment outcomes.

About the principal Investigator

Ram Rao, MD, PhD, is an Acting Assistant Professor in Pediatric Hematology, Oncology, Bone Marrow Transplant, and Cellular Therapies at the Seattle Children’s Research Institute/University of Washington. He completed his MD and PhD in Biomedical Engineering at the University of Michigan. Dr. Rao’s scientific training spans the fields of 3D cancer model development, vascularized bone tissue engineering, biomineralization, and gene therapy. He is work has been supported by the Pediatric Scientist Development Program (NIH K12) and has been selected for the Society for Pediatric Research Fellow’s Basic Research Award, the Connective Tissue Oncology Society Best Poster Award in the Bone Tumors category, and the Society for Pediatric Research David G. Nathan Award. Dr. Rao’s long-term goal is to combine his unique background in tissue engineering and biomaterials with osteosarcoma research to identify novel targets and treatment regimens to improve patient outcomes.