Julia Waldman
A5006263348- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- RNA modifications and cancer
- RNA Research and Splicing
- Molecular Biology Techniques and Applications
- Immune cells in cancer
- T-cell and B-cell Immunology
- COVID-19 Clinical Research Studies
- Neuroblastoma Research and Treatments
- Renal and related cancers
- Pancreatic and Hepatic Oncology Research
- Cancer Immunotherapy and Biomarkers
- IL-33, ST2, and ILC Pathways
- Extracellular vesicles in disease
- Cell Image Analysis Techniques
- Microscopic Colitis
- Neuroinflammation and Neurodegeneration Mechanisms
- Genomics and Chromatin Dynamics
- Advanced biosensing and bioanalysis techniques
- Colorectal Cancer Screening and Detection
- Gene expression and cancer classification
- SARS-CoV-2 and COVID-19 Research
- Neonatal Respiratory Health Research
- Inflammatory Bowel Disease
Broad Institute
2018-2024
Massachusetts Institute of Technology
2020
Howard Hughes Medical Institute
2020
Tumori Foundation
2020
Dana-Farber Cancer Institute
2020
University of Connecticut
2018
National Center on Birth Defects and Developmental Disabilities
2010
University of California, San Francisco
1993
University of Amsterdam
1967
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...
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Knowledge of circulating immune cell types and states associated with SLE remains incomplete. We profiled more than 1.2 million peripheral blood mononuclear cells (162 cases, 99 controls) multiplexed single-cell RNA sequencing (mux-seq). Cases exhibited elevated expression type 1 interferon-stimulated genes (ISGs) in monocytes, reduction naïve CD4
Understanding gene function and regulation in homeostasis disease requires knowledge of the cellular tissue contexts which genes are expressed. Here, we applied four single-nucleus RNA sequencing methods to eight diverse, archived, frozen types from 16 donors 25 samples, generating a cross-tissue atlas 209,126 nuclei profiles, integrated across tissues, donors, laboratory with conditional variational autoencoder. Using resulting atlas, highlight shared tissue-specific features...
ABSTRACT The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Cell membrane bound angiotensin-converting enzyme 2 (ACE2) associated proteases, transmembrane protease serine (TMPRSS2) Cathepsin L (CTSL), were previously identified as mediators of SARS-CoV2 cellular entry. Here, we assess cell type-specific RNA expression ACE2 , TMPRSS2 CTSL through integrated...
Abstract Human iPSC-derived kidney organoids have the potential to revolutionize discovery, but assessing their consistency and reproducibility across iPSC lines, reducing generation of off-target cells remain an open challenge. Here, we profile four human lines for a total 450,118 single show how organoid composition development are comparable fetal adult kidneys. Although cell classes largely reproducible time points, protocols, replicates, detect variability in proportions between...
Single-nucleus RNA-seq (snRNA-seq) enables the interrogation of cellular states in complex tissues that are challenging to dissociate or frozen, and opens way human genetics studies, clinical trials, precise cell atlases large organs. However, such applications currently limited by batch effects, processing, costs. Here, we present an approach for multiplexing snRNA-seq, using sample-barcoded antibodies uniquely label nuclei from distinct samples. Comparing brain cortex samples profiled with...
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...
Diabetic kidney disease (DKD), the most common cause of failure, is a frequent complication diabetes and obesity, yet to date, treatments halt its progression are lacking. We analyze single-cell transcriptomic profiles from DKD patients two mouse models at multiple time points along progression—high-fat diet (HFD)-fed mice aged 90–100 weeks BTBR ob/ob (a genetic model)—and report an expanding population macrophages with high expression triggering receptor expressed on myeloid cells 2 (TREM2)...
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...
ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) remains a treatment-refractory disease. Characterizing PDAC by mRNA profiling particularly challenging. Previously identified bulk expression subtypes were influenced contaminating stroma and have not yet informed clinical management, whereas single cell RNA-seq (scRNA-seq) of fresh tumors under-represented key types. Here, we developed robust single-nucleus (snRNA-seq) technique for frozen archival specimens used it to study both untreated...
Abstract Understanding the function of genes and their regulation in tissue homeostasis disease requires knowing cellular context which are expressed tissues across body. Single cell genomics allows generation detailed atlases human tissues, but most efforts focused on single types. Here, we establish a framework for profiling multiple body at single-cell resolution using nucleus RNA-Seq (snRNA-seq), apply it to 8 diverse, archived, frozen types (three donors per tissue). We four snRNA-seq...
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 Identifying gene regulatory targets of nuclear proteins in tissues remains a challenge. Here we describe tranuclear C ellular I ndexing T ranscriptomes and E pitopes (inCITE-seq), scalable method for measuring multiplexed intranuclear protein levels the transcriptome parallel thousands cells, enabling joint analysis TF expression vivo . We apply inCITE-seq to characterize cell state-related changes upon pharmacological induction neuronal activity mouse brain. Modeling as linear...
Abstract Profiling cellular heterogeneity in formalin-fixed paraffin-embedded (FFPE) tissues is key to characterizing clinical specimens for biomarkers, therapeutic targets, and drug responses. Here, we optimize methods isolating intact nuclei single nucleus RNA-Seq from FFPE the mouse brain, demonstrate a pilot application human specimen of lung adenocarcinoma. Our method opens way broad applications snRNA-Seq archival tissues, including samples.
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...
The human airway contains specialized rare epithelial cells whose roles in respiratory disease are not well understood. Ionocytes express the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), while chemosensory tuft asthma-associated alarmins. However, surprisingly, exceedingly few mature have been identified lung cell atlases despite ready identification of ionocytes and neuroendocrine cells. To identify progenitors define their lineage relationship to cells, we generated a deep...