Dr. Raya Saab is a Professor at the Department Pediatrics, Division of Hematology, Oncology, and Stem Cell Transplant at Stanford. She is currently section chief of Pediatric Oncology, and her clinical expertise is in pediatric sarcoma and retinoblastoma. Dr. Saab's laboratory research aims to understand oncogenic pathways involved in tumor progression and invasion to identify novel therapeutic targets, focusing on the pediatric soft tissue tumor rhabdomyosarcoma.
Dr. Saab completed her undergraduate and medical school studies at the American University of Beirut, in Lebanon, then residency in Pediatrics at Duke University Medical Center in North Carolina, and fellowship in Pediatric Hematology-Oncology at St Jude Children’s Research Hospital in Tennessee. In 2007, she joined the American University of Beirut (AUB) in Lebanon for a faculty position, in the Physician-Scientist track at the School of Medicine. At the AUB, Dr. Saab led her laboratory research group focusing on cellular senescence in tumor suppression and on rhabdomyosarcoma biology, mentoring multiple undergraduate and graduate students.
Dr. Saab's laboratory focuses on investigating molecular mechanisms of oncogene-induced tumorigenesis and tumor suppressor pathways, and oncogenic signaling in the pediatric solid tumor rhabdomyosarcoma. Their earlier work identified the tumor suppressors p53 and p18Ink4c as inhibitors of Cyclin D1-driven tumorigenesis in a pineoblastoma model, through senescence induction, and highlighted distinct roles for the the RB and p53 pathways in induction and maintenance of oncogene-induced senescence. The lab also identified CDK2 as a potential target for inducing senescence in premalignant lesions to inhibit tumor progression.
The Saab laboratory's current focus is on studying oncogenic signaling and tumor suppression in the childhood tumor rhabdomyosarcoma, to identify key mediators of invasion and metastasis, which is the most common cause of treatment failure clinically. They use preclinical in vitro and in vivo models, including murine and human cell lines, and mouse models of disease.
They have recently uncovered a paracrine role for rhabdomyosarcoma-secreted exosomes in impacting biology of stromal cells. Rhabdomyosarcoma-derived exosomes carry specific miRNA cargo that imparts an invasive and migratory phenotype on normal recipient fibroblasts, and proteomic analysis revealed specific and unique pathways relevant to the two different molecular rhabdomyosarcoma subtypes that are driven by distinct oncogenic pathways. They identified that the driver oncogene in fusion-positive rhabdomyosarcoma, PAX3-FOXO1, modulates exosome cargo to promote invasion, migration, and angiogenic properties, and identified specific microRNA and protein cargo acting as effectors of PAX3-FOXO1 exosome-mediated signaling, including modulation of oxidative stress response and cell survival signaling.
The lab's ongoing work is focused on interrogating specific paracrine signaling pathways and molecular mechanisms of metastatic disease progression in rhabdomyosarcoma, for potential therapeutic targeting.