Judit Jané‐Valbuena
A5007565104- Melanoma and MAPK Pathways
- Single-cell and spatial transcriptomics
- Cutaneous Melanoma Detection and Management
- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- Bioinformatics and Genomic Networks
- Cancer Immunotherapy and Biomarkers
- Cell Image Analysis Techniques
- Advanced Proteomics Techniques and Applications
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Immune cells in cancer
- Radiomics and Machine Learning in Medical Imaging
- Diverse Scientific and Economic Studies
- Genomics and Chromatin Dynamics
- Computational Drug Discovery Methods
- T-cell and B-cell Immunology
- RNA regulation and disease
- Protein Kinase Regulation and GTPase Signaling
- Viral gastroenteritis research and epidemiology
- Gene expression and cancer classification
- Colorectal Cancer Screening and Detection
- Mathematical Biology Tumor Growth
- Cardiovascular Function and Risk Factors
- Medical Imaging Techniques and Applications
Broad Institute
2010-2024
Massachusetts Institute of Technology
2011-2023
Dana-Farber Cancer Institute
2010-2017
Harvard University
2002-2016
Brigham and Women's Hospital
2010
Massachusetts General Hospital
2010
Municipal Institute for Medical Research
2007
University of Wisconsin–Madison
2002
Institute of Virology of the Slovak Academy of Sciences
1999
To explore the distinct genotypic and phenotypic states of melanoma tumors, we applied single-cell RNA sequencing (RNA-seq) to 4645 single cells isolated from 19 patients, profiling malignant, immune, stromal, endothelial cells. Malignant within same tumor displayed transcriptional heterogeneity associated with cell cycle, spatial context, a drug-resistance program. In particular, all tumors harbored malignant two states, such that characterized by high levels MITF transcription factor also...
Abstract Single-cell genomics is essential to chart tumor ecosystems. Although single-cell RNA-Seq (scRNA-Seq) profiles RNA from cells dissociated fresh tumors, single-nucleus (snRNA-Seq) needed profile frozen or hard-to-dissociate tumors. Each requires customization different tissue and types, posing a barrier adoption. Here, we have developed systematic toolbox for profiling clinical samples using scRNA-Seq snRNA-Seq, respectively. We analyzed 216,490 nuclei 40 across 23 specimens spanning...
Immune responses to cancer are highly variable, with mismatch repair-deficient (MMRd) tumors exhibiting more anti-tumor immunity than repair-proficient (MMRp) tumors. To understand the rules governing these varied responses, we transcriptionally profiled 371,223 cells from colorectal and adjacent normal tissues of 28 MMRp 34 MMRd individuals. Analysis 88 cell subsets their 204 associated gene expression programs revealed extensive transcriptional spatial remodeling across discover hubs...
Identifying transcript location in cells where specific RNAs occur within a cell or tissue has been limited by technology and imaging capabilities. Expansion microscopy allowed for better visualization of small structures expanding the tissues with polymer- hydrogel-based system. Alon et al. combined expansion long-read situ RNA sequencing, resulting more precise transcripts. This method, termed “ExSeq” was used to detect RNAs, both new transcripts those previously demonstrated localize...
Signaling pathways are orchestrated by post-translational modifications (PTMs) such as phosphorylation. However, pathway analysis of PTM data sets generated mass spectrometry (MS)-based proteomics is typically performed at a gene-centric level because the lack appropriately curated signature databases and bioinformatic tools that leverage site-specific information. Here we present first version PTMsigDB, database modification signatures perturbations, kinase activities signaling from more...
Tissue biology involves an intricate balance between cell-intrinsic processes and interactions cells organized in specific spatial patterns, which can be respectively captured by single-cell profiling methods, such as RNA-seq (scRNA-seq), histology imaging data, Hematoxylin-and-Eosin (H&E) stains. While profiles provide rich molecular information, they challenging to collect routinely do not have resolution. Conversely, histological H&E assays been a cornerstone of tissue pathology for...
SUMMARY Neuroblastoma is a pediatric cancer arising from the developing sympathoadrenal lineage with complex inter- and intra-tumoral heterogeneity. To chart this complexity, we generated comprehensive cell atlas of 55 neuroblastoma patient tumors, collected two institutions, spanning range clinical, genetic, histologic features. Our combines single-cell/nucleus RNA-seq (sc/scRNA-seq), bulk RNA-seq, whole exome sequencing, DNA methylation profiling, spatial transcriptomics, proteomic...
Copy gains involving chromosome 7p represent one of the most common genomic alterations found in melanomas, suggesting presence "driver" cancer genes. We identified several tumor samples that harbored focal amplifications situated at peak gains, which minimal overlapping region spanned ETV1 oncogene. Fluorescence situ hybridization analysis revealed copy spanning locus >40% cases, with amplification (>6 copies/cell) present 13% primary and 18% metastatic melanomas. Melanoma cell lines,...
9502 Background: Previous analysis of COMBI-d (NCT01584648) showed that D+T compared with D monotherapy improved ORR (69% [95% CI, 62%-75%] vs 53% 46%-60%]; P = 0.0014), reduced risk progression (HR, 0.67 0.53-0.84]; 0.0004) and death 0.71 0.55-0.92]; 0.0107), increased 2-y OS rate (51% 42%) in BRAFV600–mutant melanoma. Methods: In this phase 3, randomized, double-blind study, pts histologically confirmed unresectable stage IIIC or IV, BRAF V600E/K–mutant melanoma were randomized 1:1 to...
Abstract The SARS-CoV-2 pandemic has caused over 1 million deaths globally, mostly due to acute lung injury and respiratory distress syndrome, or direct complications resulting in multiple-organ failures. Little is known about the host tissue immune cellular responses associated with COVID-19 infection, symptoms, lethality. To address this, we collected tissues from 11 organs during clinical autopsy of 17 individuals who succumbed COVID-19, a bank approximately 420 specimens. We generated...
Combined treatment with dabrafenib and trametinib (CombiDT) achieves clinical responses in only about 15% of patients BRAF inhibitor (BRAFi)-refractory metastatic melanoma contrast to the higher response rate observed BRAFi-naïve patients. Identifying correlates mechanisms resistance this population will facilitate management rational therapeutic development.To determine benefit from CombiDT therapy BRAFi-refractory melanoma.Single-center, single-arm, open-label phase 2 trial V600 resistant...
Abstract: Methods for highly multiplexed RNA imaging are limited in spatial resolution, and thus their ability to localize transcripts nanoscale subcellular compartments. We adapt expansion microscopy, which physically expands biological specimens, long-read untargeted targeted situ sequencing. applied sequencing (ExSeq) mouse brain, yielding readout of thousands genes, including splice variants novel transcripts. Targeted ExSeq yielded nanoscale-resolution maps RNAs throughout dendrites...
Abstract Although metastatic disease is the leading cause of cancer-related deaths, its tumor microenvironment remains poorly characterized due to technical and biospecimen limitations. In this study, we assembled a multi-modal spatial cellular map 67 biopsies from 60 patients with breast cancer across diverse clinicopathological features nine anatomic sites detailed clinical annotations. We combined single-cell or single-nucleus RNA sequencing for all panel four expression assays...