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Proteogenomic Discovery of Immunotherapeutic Targets in Rhabdomyosarcoma
Start Date: 2/7/2022Start Time: 1:00 PM
End Date: 2/7/2022End Time: 3:00 PM
Event Description
BIOMED PhD Research Proposal

Proteogenomic Discovery of Immunotherapeutic Targets in Rhabdomyosarcoma
Rawan Shraim, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University

Bioinformatics Scientist I
Center for Childhood Cancer (CCCR)
Department of Biomedical and Health Informatics (DBHi)
Children’s Hospital of Philadelphia (CHOP)

John M. Maris, MD
Giulio D'Angio Professor of Pediatric Oncology
Perelman School of Medicine at the University of Pennsylvania
Division of Oncology, Children's Hospital of Philadelphia (CHOP)

Sharon J. Diskin, PhD
Associate Professor of Pediatrics
Genomics And Computational Biology, Cell And Molecular Biology
Children's Hospital of Philadelphia (CHOP)

Ahmet Sacan, PhD
Associate Teaching Professor
School of Biomedical Engineering, Science and Health Systems
Drexel University

Rhabdomyosarcoma is the most common soft tissue cancer diagnosed in children, adolescents, and young adults, comprising 3-4% of all childhood cancers. There are two main types of rhabdomyosarcoma defined by the presence or absence of a chromosomal translocation event that creates a fusion oncoprotein, fusion(+) and fusion(-).Treatment is commonly multi-modal involving surgery, radiation, and chemotherapy and has not substantively changed over the last four decades. Approximately 90% of patients with localized low-risk disease are cured with multi-modal therapy; however, the survival rate for patients with metastatic disease remains mired at 30% or less and relapsed disease is typically lethal.

There are currently no approved immunotherapies or targeted therapies for rhabdomyosarcoma and there have been no significant improvements in survival outcomes for patients despite multiple randomized controlled trials of various chemotherapy combinations. Thus, there is an urgent need to develop precise targeted treatments for rhabdomyosarcoma patients based on the underlying biology of the disease, which is the long-term goal of our study. The objective is to identify cell surface oncoproteins that are uniquely expressed in RMS (compared to normal childhood tissues) that will be developed as targets for novel immunotherapies. We hypothesize that an integrative proteogenomic analysis of rhabdomyosarcoma and normal tissues will identify and prioritize surface proteins preferentially expressed in rhabdomyosarcoma, or rhabdomyosarcoma subtypes, to undergo functional validation as a candidate immunotherapeutic target.

The test our hypothesis we will integrate inhouse generated and publicly available rhabdomyosarcoma and healthy tissue proteomic, transcriptomic, and genomic datasets along with functional databases in combination with a prioritization algorithm to rank surface proteins as putative immunotherapeutic targets for rhabdomyosarcoma and rhabdomyosarcoma subtypes. After computationally prioritizing targets, we plan to validate expression and functional relevance of top prioritized cell surface proteins using in vitro assays. Our rationale is that novel immunotherapeutic targets have been identified in other pediatric cancers such as neuroblastoma using a similar proteogenomic approach, leading to new immunotherapy development.
Contact Information:
Name: Natalia Broz
Rawan Shraim
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