A5071500080- Single-cell and spatial transcriptomics
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Renal and related cancers
- Pancreatic function and diabetes
- Diabetes and associated disorders
- Renal Diseases and Glomerulopathies
- ATP Synthase and ATPases Research
- Inflammatory Bowel Disease
- Gene expression and cancer classification
- Diabetes Management and Research
- Chronic Kidney Disease and Diabetes
- Immunodeficiency and Autoimmune Disorders
- Drug Transport and Resistance Mechanisms
- Bone and Joint Diseases
- Genetics, Aging, and Longevity in Model Organisms
- Polyamine Metabolism and Applications
- Eosinophilic Esophagitis
- Wnt/β-catenin signaling in development and cancer
- Cancer Cells and Metastasis
- Mathematical Biology Tumor Growth
- Echinoderm biology and ecology
- Immune Cell Function and Interaction
- Advanced Proteomics Techniques and Applications
- Whipple's Disease and Interleukins
University of Pennsylvania
2017-2024
Enable Biosciences (United States)
2023-2024
Menlo School
2023-2024
Kyowa Kirin (Japan)
2017-2023
The University of Tokyo
2012-2019
Kyowa Kirin International (United Kingdom)
2017
Innovative Technology Laboratories (United States)
2017
Kyowa Hakko Kirin (Singapore)
2017
Osaka University
2012
Touring the kidney, cell by Our kidneys play a critical role in keeping us healthy, fact of which we are reminded several times each day. This organ's cellular complexity has hindered progress understanding mechanisms underlying chronic kidney disease, affects 10% world's population. Using single-cell transcriptional profiling, Park et al. produced comprehensive atlas healthy mouse (see Perspective Humphreys). An unexpected type collecting duct appears to be transitional state between two...
Abstract Determining the epigenetic program that generates unique cell types in kidney is critical for understanding cell-type heterogeneity during tissue homeostasis and injury response. Here, we profile open chromatin gene expression developing adult mouse kidneys at single resolution. We show reliance of on distal regulatory elements (enhancers). reveal key type-specific transcription factors major gene-regulatory circuits cells. Dynamic changes nephron progenitor differentiation...
Conditions of the tumor microenvironment, such as hypoxia and nutrient starvation, play critical roles in cancer progression. However, role acidic extracellular pH progression is not studied extensively that hypoxia. Here, we show (pH 6.8) triggered activation sterol regulatory element-binding protein 2 (SREBP2) by stimulating nuclear translocation promoter binding to its targets, along with intracellular acidification. Interestingly, inhibition SREBP2, but SREBP1, suppressed upregulation...
Psoriasis vulgaris and other chronic inflammatory diseases improve markedly with therapeutic blockade of interleukin-23 (IL-23) signaling, but the genetic mechanisms underlying clinical responses remain poorly understood. Using single-cell transcriptomics, we profiled immune cells isolated from lesional psoriatic skin before during IL-23 blockade. In clinically responsive patients, a transcriptional signature in skin-resident memory T was strongly attenuated. contrast, patients were...
Long noncoding RNAs play a pivotal role in tumor progression, but their cancer cells the nutrient-starved microenvironment remains unknown. Here, we show that nutrient starvation-responsive long RNA, JHDM1D antisense 1 (JHDM1D-AS1), promotes tumorigenesis by regulating angiogenesis response to starvation. Expression of JHDM1D-AS1 was increased cells. In addition, expression clinical samples compared normal tissue. Stable human pancreatic (PANC-1 and AsPC-1) promoted cell growth vitro...
Tolerance to severe tumor microenvironments, including hypoxia and nutrient starvation, is a common feature of aggressive cancer cells can be targeted. However, metabolic alterations that support upon starvation are not well understood. Here, by comprehensive metabolome analyses, we show glutamine deprivation leads phosphoethanolamine (PEtn) accumulation in via the downregulation PEtn cytidylyltransferase (PCYT2), rate-limiting enzyme phosphatidylethanolamine biosynthesis. correlated with...
Tissues are organized into anatomical and functional units at different scales. New technologies for high-dimensional molecular profiling in situ have enabled the characterization of structure-function relationships increasing detail. However, it remains a challenge to consistently identify key across experiments, tissues, disease contexts, task that demands extensive manual annotation. Here, we present spatial cellular graph partitioning (SCGP), flexible method unsupervised annotation...
Multidrug resistance-associated protein 4 (MRP4/ABCC4) makes a vital contribution to the bodily distribution of drugs and endogenous compounds because its cellular efflux abilities. However, little is known about mechanism regulating cell surface expression. MRP4 has PDZ-binding motif, which potential sequence that modulates membrane expression via interaction with PDZ adaptor proteins. To investigate this possible relationship, we performed GST pull-down assays subsequent analysis...
Kidney allograft rejections are orchestrated by a variety of immune cells. Because the complex histopathologic features, accurate pathological diagnosis poses challenges even for expert pathologists. The objective this study was to unveil novel spatial indices associated with transplant rejection using bioinformatic approach 36-plex immunofluorescence image data.
Abstract An acidic tumor microenvironment plays a critical role in progression. However, understanding of metabolic reprogramming tumors response to extracellular pH has remained elusive. Using comprehensive metabolomic analyses, we demonstrated that (pH 6.8) leads the accumulation N1-acetylspermidine, protumor metabolite, through up-regulation expression spermidine/spermine acetyltransferase 1 (SAT1). Inhibition SAT1 suppressed intra- and N1-acetylspermidine at pH. Conversely,...
Abstract Type 1 diabetes (T1D) is an autoimmune disease of only partially defined etiology in which immune cells destroy insulin-producing beta cells. Using single-cell transcriptomics and advanced analytical strategy to assess pancreatic islets T1D, autoantibody-positive, non-diabetic organ donors, we identified both canonical cell types rare insulin-expressing with a hybrid mixture endocrine exocrine gene signatures within all donors. We further found elevated expression MHC Class II...
Abstract A key limitations to understand kidney function and disease development has been that specific cell types responsible for homeostatic or phenotypes have not defined at the molecular level. To fill this gap, we characterized 57,979 cells from healthy mouse kidneys using unbiased single-cell RNA sequencing. We show genetic mutations present with similar mostly affect genes are expressed in a single unique differentiated type. On other hand, found unexpected plasticity of epithelial...
Conditions of the tumor microenvironment, such as hypoxia or nutrient starvation, play critical roles in cancer progression and malignancy. However, role acidic extracellular pH aggressiveness its underlying mechanism has not been extensively studied compared to hypoxic starvation conditions. In addition, a well-defined culture method mimic microenvironment fully reported. Here we present simple vitro maintain using reduced bicarbonate increased lactate HCl concentrations medium. The medium...
ABSTRACT Aims/Hypothesis Diabetic kidney disease (DKD) remains a significant cause of morbidity and mortality in people with diabetes. Though animal models have taught us much about the molecular mechanisms DKD, translating these findings to human requires greater knowledge changes caused by diabetes kidneys. Establishing this base building carefully curated, reliable, complete repositories tissue, as well tissue proteomics platforms capable simultaneous, spatially resolved examination...
Abstract Determining the epigenetic program that generates unique cell types in kidney is critical for understanding cell-type heterogeneity during tissue homeostasis and injury response. Here, we profiled open chromatin gene expression developing adult mouse kidneys at single resolution. We show reliance of on distal regulatory elements (enhancers). define key type-specific transcription factors major gene-regulatory circuits cells. Dynamic changes nephron progenitor differentiation...
ABSTRACT Cytokines mediating epithelial and immune cell interactions modulate mucosal healing-a process that goes awry with chronic inflammation as in inflammatory bowel disease. TNFSF13 is a cytokine important for B maturation function, but roles putative contribution to disease are poorly understood. We evaluated functional consequences of novel monoallelic variant using biopsies, tissue-derived colonoids induced pluripotent stem (iPSC)-derived colon organoids. exhibited >50% reduction...