Mentor Areas
Despite the use of intensive multimodal therapy for neuroblastoma, approximately one-half of children still die from this disease. Dr. Bosse's laboratory focuses on the development of new immune-based therapies for this embryonal malignancy of the developing nervous system. Through these studies, Dr. Bosse and his colleagues hope to both improve their understanding of the critical biologic mechanisms driving neuroblastoma tumorigenesis and to translate new transformative immunotherapeutics to the clinic.
To this end, Dr. Bosse and his colleagues have discovered that the lineage-restricted oncoprotein, glypican-2 (GPC2), is robustly and selectively expressed on the surface of neuroblastomas and that this molecule is essential to neuroblastoma tumorigenesis. They are now focused on defining the biology of neuroblastoma’s dependence on GPC2 and developing immunotherapeutic approaches targeting GPC2, including antibody-drug conjugates and chimeric antigen receptor (CAR) T cells. Using their immunotherapeutic target discovery algorithm and validation platform, they are also developing additional differentially expressed neuroblastoma cell surface molecules for immune-based therapies. This work is done as part of the St. Baldricks-Stand Up To Cancer Immunogenomics Team.
An additional project in Dr. Bosse's laboratory is focused on the serial sequencing of circulating tumor (ctDNA) from neuroblastoma patients to define tumor heterogeneity and clonal evolution while children are receiving both conventional chemoradiotherapies and also more targeted therapeutics. Dr. Bosse anticipates these efforts may both help define a role for ctDNA profiling in the clinical care of children with neuroblastoma and other pediatric solid tumors and also identify novel mutated driver oncogenes that warrant additional functional validation.
Finally, Dr. Bosse's laboratory is also interested in defining the functional implications of neuroblastoma-associated germline genetic variation, with a particular interest in describing the role of common and rare genetic variation in the regulation of BARD1 gene expression and how these alterations collectively contribute to neuroblastoma predisposition.
Description:
- Investigate the regulation, function, and immunotherapeutic targetability of GPC2 in neuroblastoma, pediatric brain tumors, and other aggressive solid tumors.
- Optimize next-generation GPC2 CAR T cells and antibody-drug conjugates for neuroblastoma and other cancers.
- Investigate the mechanism of immune-escape from GPC2-targeted (or other) immunotherapies.
- Develop immunotherapies towards other prioritized neuroblastoma cell surface molecules.
- Define the role of neuroblastoma extracellular vesicles in tumorigenesis, immune evasion, and resistance to immunotherapy.
- Define the functional relevance of circulating tumor (ctDNA)-defined mutations in neuroblastoma progression and therapeutic resistance.
Preferred Qualifications
An interest in cancer biology, hard working, and ability to dedicate effort to laboratory's mission is required. Molecular biology experience a plus.
Project Website
Learn more about the researcher and/or the project here. Bosse Laboratory
Details:
Preferred Student Year
First-year, Second-Year, Junior, Senior
Academic Term
Fall, Spring, Summer
I prefer to have students start during the above term(s).Volunteer
Yes
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Yes
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Yes
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