School of Medicine
Showing 71-80 of 111 Results
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Sneha Ramakrishna
Assistant Professor of Pediatrics (Hematology/Oncology)
BioSneha Ramakrishna obtained her B. A. from the University of Chicago and her M.D. from the Cleveland Clinic Lerner College of Medicine at Case Western Reserve University. In medical school, through the Howard Hughes Medical Research Scholar Award, she joined Dr. Crystal Mackall’s laboratory, where she designed and developed various GD2 CAR-Ts and tested them in preclinical models. During her residency training in Pediatrics at the Children’s Hospital of Philadelphia, she cared for some of the first patients treated with CD19 CAR T cells, learning the power of this therapy first-hand. During her fellowship in Pediatric Hematology/Oncology at the Johns Hopkins/National Cancer Institute combined program, she worked with Dr. Terry Fry. She evaluated the mechanism of CD22 CAR T cell relapse in patients by developing an antigen escape model and establishing a deeper understanding of the effects of antigen density on CAR-T phenotype, expansion, and persistence (Fry…Ramakrishna…Mackall Nat Med, 2018; Ramakrishna, et al., Clinical Cancer Research, 2019). Since arriving at Stanford, Dr. Ramakrishna leads an interdisciplinary team that designs, develops, and successfully implements a robust correlative science platform for our novel CAR-T therapies. Analyzing patient samples from our first-in-human GD2 CAR-T trial (NCT04196413) treating a universally fatal cancer, diffuse midline glioma (DMG), we identified that intracerebroventricular CAR-T administration correlates with enhanced pro-inflammatory cytokines and reduced immunosuppressive cell populations in cerebrospinal fluid as compared to intravenous CAR-T administration (Majzner*, Ramakrishna*, et al., Nature 2022 *co-first authors). Her research program evaluates unique sets of patient samples using novel single-cell immune profiling to identify the drivers of CAR-T success or failure. Building on these findings, her team assesses approaches to enhance CAR-T efficacy and translate these findings to the clinic.
Clinically, Dr. Ramakrishna cares for children with solid tumors and treats hematologic, solid, and brain tumor pediatric patients with CAR T cell therapies in the Cancer Cellular Therapies program. -
Raya Saab
Lindhard Family Professor of Pediatric Cancer Biology
BioOur laboratory focuses on investigating molecular mechanisms of oncogene-induced tumorigenesis and tumor suppressor pathways, and oncogenic signaling in the pediatric solid tumor rhabdomyosarcoma. Our 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. We also identified CDK2 as a potential target for inducing senescence in premalignant lesions to inhibit tumor progression.
Our 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. We use preclinical in vitro and in vivo models, including murine and human cell lines, and mouse models of disease.
We 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. We 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.
Our ongoing work is focused on interrogating specific paracrine signaling pathways and molecular mechanisms of metastatic disease progression in rhabdomyosarcoma, for potential therapeutic targeting. -
Julien Sage
Elaine and John Chambers Professor of Pediatric Cancer and Professor of Genetics
On Partial Leave from 04/22/2024 To 06/24/2024Current Research and Scholarly InterestsWe investigate the mechanisms by which normal cells become tumor cells, and we combine genetics, genomics, and proteomics approaches to investigate the differences between the proliferative response in response to injury and the hyperproliferative phenotype of cancer cells and to identify novel therapeutic targets in cancer cells.
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Kathleen M. Sakamoto
Shelagh Galligan Professor in the School of Medicine
Current Research and Scholarly InterestsMy research focuses on the molecular pathways that regulate normal and aberrant blood cell development, including acute leukemia and bone marrow failure syndromes. We are also studying novel drugs for treatment of cancer.
