MIB Agents OsteoBites and osTEAo

The Rao Lab at Seattle Children's Research Institute developed a three-dimensional (3D) tissue-engineered model of osteosarcoma to investigate the effects of the extracellular matrix on malignant cell function. The study demonstrated that culturing osteosarcoma (OS) cells within a 3D collagen matrix induced unique cellular responses, altered morphology, enhanced tumorigenic behavior, and reduced chemosensitivity compared to cells cultured in 2D collagen or on standard tissue culture plastic. They identified overexpression of drug efflux pumps as a key mechanism of chemoresistance and further showed that a tyrosine kinase inhibitor could suppress drug efflux activity, thereby enhancing the efficacy of standard chemotherapeutic agents.

While this earlier study examined the effects of a single collagen concentration on osteosarcoma phenotype, clinical solid tumors are characterized by altered extracellular microarchitecture, including increased matrix density and stiffness. These changes restrict drug transport and limit chemotherapy-induced cell death.

Dr. Rao will present findings from engineered tumor models incorporating varying matrix densities and demonstrate how matrix density influences osteosarcoma function. This work was funded by the 2025 Outsmarting Osteosarcoma Young Investigator Hope Award.

Dr. Rao is a Pediatric Hematologist Oncologist at the Seattle Children's Hospital and a Principal Investigator in the Ben Towne Center for Childhood Cancer and Blood Disorders Research at the Seattle Children's Research Institute. His lab harnesses biomaterials and tissue engineering technologies to design 3D models of osteosarcoma to understand how cell-matrix interactions lead to chemoresistance.

Osteosarcoma Webinar Series: Ali Cihan, PhD, a research scholar at Memorial Sloan Kettering Cancer Center, will discuss his OutSmarting Osteosarcoma funded work on targeting EPHA2 with dual-armored CAR T cells for immunotherapy in pediatric osteosarcoma.

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.

Dr. Aafrin Pettiwala from UCSF joins us on OsteoBites to discuss her OutSmarting Osteosarcoma funded work on identifying mechanisms of chemoresistance in metastatic osteosarcoma using molecular barcoding.

The presentation covers how intratumoral heterogeneity drives chemoresistance and metastasis in osteosarcoma by using lineage tracing (CaTCH) and patient-derived xenograft models. She has identified resistant and metastatic cell subpopulations and their molecular vulnerabilities, and further research seeks to uncover new therapeutic targets to improve treatment outcomes for metastatic osteosarcoma patients.

Dr. Pettiwala 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.

Amy LeBlanc, DVM, a board-certified veterinary oncologist, Senior Scientist, and the Director of the intramural NCI’s Comparative Oncology Program, will review canine osteosarcoma and the clinical, biologic, and molecular features that make it a relevant animal-patient model for humans. She will share new data from the NCI's Comparative Oncology Program regarding MYC, and its value as a predictive biomarker for the disease in canine patients.

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.

Osteosarcoma Webinar Series: Corey Weistuch, PhD, an Assistant Attending Physicist in the Service for Predictive Informatics within the Department of Medical Physics at Memorial Sloan Kettering Cancer Center, will discuss his OutSmarting Osteosarcoma funded work on implementing personalized, adaptive therapies in osteosarcoma.

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.

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

This episode of osTEAo focuses on the sibling side of cancer—celebrating the strength and support siblings bring to their families, and uplifting those who have lost a sibling and continue showing up every day. As the family focuses shift toward treatment and recovery, siblings often carry things quietly, finding ways to support through hospital visits, shared laughs, and simply being there. This episode highlights their impact and thanks them for being such an important part of the journey.

Donate items to our OutBidding Osteosarcoma auction: https://form-usa.keela.co/in-kind-donation-2026

Osteosarcoma Webinar Series: David Ulmert, MD, PhD, an Associate Professor at UCLA, discusses his OutSmarting Osteosarcoma funded work (Because of Sydney) on high-throughput characterization of pathobiological responses in osteosarcoma tumors treated with LRRC15-targeted radiotherapy to uncover curative co-treatment approaches.

Dr. Ulmert will discuss his lab's work investigating how osteosarcoma responds to LRRC15-targeted radiotherapy, with patient translation anticipated this year. Using high-throughput technologies, the team will identify biomarkers, predictive models, and key transcriptional regulators driving the TGFβ–LRRC15 axis. He will review how radiopathobiological changes and immune reprogramming are being mapped to uncover druggable events and inform co-treatment strategies, accelerating near-term impact on patient studies and next-generation therapeutic development.

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.

The first episode of 2026 keeps it real about what the New Year actually feels like when osteosarcoma is still part of everyday life. Mia and Sammy are joined by Sloane and Mackenzie to talk through pain, recovery, scans, insurance stress, and the emotional weight January can bring. There’s no pressure to have it all figured out—just honest conversation, shared experiences, and hope focused on small, bite-sized goals and taking things one day at a time.

Osteosarcoma Webinar Series: Joseph Skeate, PhD, an Assistant Professor at the University of Minnesota, discusses his OutSmarting Osteosarcoma funded work (Because of Annaleigh) on next generation dual-CAR gamma delta T cells for the treatment of pediatric osteosarcoma.

In this presentation, Dr. Skeate will provide an overview of the next-generation genome engineering strategies deployed for this project and share updates on the development of a gamma-delta chimeric antigen receptor (CAR) T cell therapy for treating osteosarcoma. He will describe how the team is combining non-viral transposon insertion of a CAR transgene with targeted gene modification using an Adenine Base Editor to enhance T cell function in the presence of suppressive factors characteristic of osteosarcoma tumors.

Dr Joseph Skeate is an Assistant Professor in the Division of Pediatric Hematology/Oncology at the University of Minnesota. He obtained his PhD in Medical Biology from the University of Southern California Keck School of Medicine. Following his doctoral work, he completed a postdoctoral fellowship at the University of Minnesota under the mentorship of Drs Branden Moriarity and Beau Webber. During this time, he developed a hyperactive transposon system and deployed novel genome engineering approaches using Cas9 systems, creating a powerful toolkit for rapid non-viral engineering and preclinical testing of primary human cells. Leveraging his background and expertise in immunology and genome engineering, his lab now focuses on developing next-generation cellular therapies for rare pediatric disease, including osteosarcoma.

Osteosarcoma Webinar Series: Izuchukwu Ibe, MD, a musculoskeletal oncologist, Associate Professor, and Residency Program Director at the University of Mississippi Medical Center joins us on OsteoBites to discuss insights and highlights from the Musculoskeletal Tumor Society (MSTS) December 2025 Annual Meeting, December 3-5 in Mexico City.

Dr. Ibe is a Musculoskeletal Oncologist with a residency from Yale and a Fellowship from the University of Toronto. He is passionate about educating patients and families with a sarcoma diagnosis and channels this through his Sarcoma Insights podcasts. He enjoys soccer and spending time with his family.