Pichai Raman
A5068529122- Neuroblastoma Research and Treatments
- Cancer Genomics and Diagnostics
- Glioma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Pancreatic and Hepatic Oncology Research
- Cancer therapeutics and mechanisms
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Cancer-related molecular mechanisms research
- Neuroendocrine Tumor Research Advances
- Lung Cancer Research Studies
- Ubiquitin and proteasome pathways
- Ferroptosis and cancer prognosis
- CAR-T cell therapy research
- PARP inhibition in cancer therapy
- Peroxisome Proliferator-Activated Receptors
- RNA Research and Splicing
- Bioinformatics and Genomic Networks
- Radiomics and Machine Learning in Medical Imaging
- Genetics, Bioinformatics, and Biomedical Research
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- Immunotherapy and Immune Responses
- interferon and immune responses
- Cancer Immunotherapy and Biomarkers
Children's Hospital of Philadelphia
2015-2024
GlaxoSmithKline (Netherlands)
2021
University of Pennsylvania
2014-2019
Drexel University
2015-2019
Novartis (Switzerland)
2010-2015
Beth Israel Deaconess Medical Center
2014
Harvard University
2014
Dana-Farber Cancer Institute
2014
Novartis (United States)
2013
Pathways Behavioral Services
2010-2013
Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into biology. Here we present comprehensive analysis of genetic alterations in pan-cancer cohort including 961 tumours from children, adolescents, young adults, comprising 24 distinct molecular cancer. Using standardized workflow, identified marked terms mutation frequency significantly mutated genes comparison previously analysed adult cancers....
The CD19 antigen, expressed on most B-cell acute lymphoblastic leukemias (B-ALL), can be targeted with chimeric antigen receptor-armed T cells (CART-19), but relapses epitope loss occur in 10% to 20% of pediatric responders. We detected hemizygous deletions spanning the locus and de novo frameshift missense mutations exon 2 some relapse samples. However, we also discovered alternatively spliced mRNA species, including one lacking 2. Pull-down/siRNA experiments identified SRSF3 as a splicing...
The calcium-activated chloride channel anoctamin 1 ( ANO1 ) is located within the 11q13 amplicon, one of most frequently amplified chromosomal regions in human cancer, but its functional role tumorigenesis has remained unclear. region ∼15% breast cancers. Whether tumors, extent to which gene amplification contributes overexpression, and whether overexpression important for tumor maintenance have unknown. We found that highly expressed cancer cell lines primary tumors. Amplification...
We report a comprehensive proteogenomics analysis, including whole-genome sequencing, RNA and proteomics phosphoproteomics profiling, of 218 tumors across 7 histological types childhood brain cancer: low-grade glioma (n = 93), ependymoma (32), high-grade (25), medulloblastoma (22), ganglioglioma (18), craniopharyngioma (16), atypical teratoid rhabdoid tumor (12). Proteomics data identify common biological themes that span boundaries, suggesting treatments used for one type may be applied...
Inhibiting a specific isoform of TGFβ augments the effectiveness checkpoint blockade therapy in cancer treatment.
The HERBY trial was a phase II open-label, randomized, multicenter evaluating bevacizumab (BEV) in addition to temozolomide/radiotherapy patients with newly diagnosed non-brainstem high-grade glioma (HGG) between the ages of 3 and 18 years. We carried out comprehensive molecular analysis integrated pathology, radiology, immune profiling. In post-hoc subgroup analysis, hypermutator tumors (mismatch repair deficiency somatic POLE/POLD1 mutations) those biologically resembling pleomorphic...
Abstract Chromosome 6p22 was identified recently as a neuroblastoma susceptibility locus, but its mechanistic contributions to tumorigenesis are yet undefined. Here we report that the most highly significant single-nucleotide polymorphism (SNP) associations reside within CASC15, long noncoding RNA define tumor suppressor at 6p22. Low-level expression of short CASC15 isoform (CASC15-S) associated with advanced and poor patient survival. In human cells, attenuating CASC15-S increased cellular...
Accelerating cures for children with cancer remains an immediate challenge as a result of extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving diagnosis relapsed disease, limited therapeutic options. To systematically prioritize rationally test novel agents in preclinical murine models, researchers the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs)—many which refractory to current...
Neuroblastoma is characterized by a relative paucity of recurrent somatic mutations at diagnosis. However, recent studies have shown that the mutational burden increases relapse, likely as result clonal evolution mutation-carrying cells during primary treatment. To inform development personalized therapies, we sought to further define frequency potentially actionable in neuroblastoma, both diagnosis and after chemotherapy. We performed retrospective study determine mutation frequency, only...
Somatic genetic testing is rapidly becoming the standard of care in many adult and pediatric cancers. Previously, approach was single-gene or focused multigene testing, but centers have moved towards broad-based next-generation sequencing (NGS) panels. Here, we report laboratory validation clinical utility a large cohort NGS somatic results diagnosis, prognosis, treatment wide range Subjects were accrued retrospectively at single quaternary-care hospital. Sequence analyses performed on 367...
The presence of an ALK aberration correlates with inferior survival for patients high-risk neuroblastoma. emergence inhibitors such as crizotinib has provided novel treatment opportunities. However, certain mutations result in de novo resistance, and a phase I trial showed lack response harboring those mutations. Thus, understanding mechanisms resistance defining circumvention strategies the clinic is critical.The sensitivity human neuroblastoma-derived cell lines, line-derived,...
Englerin A is a structurally unique natural product reported to selectively inhibit growth of renal cell carcinoma lines. large scale phenotypic profiling experiment (CLiP) englerin on ¬over 500 well characterized cancer lines showed that inhibits subset tumor from many lineages, not just carcinomas. Expression the TRPC4 cation channel was line feature best correlated with sensitivity A, suggesting hypothesis efficacy target for A. Genetic experiments demonstrate expression both necessary...
Cancer classification is foundational for patient care and oncology research. Systems such as International Classification of Diseases Oncology (ICD-O), Systematized Nomenclature Medicine Clinical Terms (SNOMED-CT), National Institute Thesaurus (NCIt) provide large sets cancer terminologies but they lack a dynamic modernized platform that addresses the fast-evolving needs in clinical reporting genomic sequencing results associated research.To meet these needs, we have developed OncoTree, an...
Abstract The degree of metastatic disease varies widely among patients with cancer and affects clinical outcomes. However, the biological functional differences that drive extent metastasis are poorly understood. We analyzed primary tumors paired metastases using a multifluorescent lineage-labeled mouse model pancreatic ductal adenocarcinoma (PDAC)—a tumor type in which most present metastases. Genomic transcriptomic analysis revealed an association between burden gene amplification or...
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Pediatric brain and spinal cancers are collectively the leading disease-related cause of death in children; thus, we urgently need curative therapeutic strategies for these tumors. To accelerate such discoveries, Children's Brain Tumor Network (CBTN) Pacific Neuro-Oncology Consortium (PNOC) created a systematic process tumor biobanking, model generation, sequencing with immediate access to harmonized data. We leverage data establish OpenPBTA, an open collaborative project over 40 scalable...