A5060150538- Cancer Cells and Metastasis
- Single-cell and spatial transcriptomics
- Renal and related cancers
- Digestive system and related health
- Neonatal Respiratory Health Research
- Retinal Diseases and Treatments
- Congenital Diaphragmatic Hernia Studies
- Bat Biology and Ecology Studies
- Distributed and Parallel Computing Systems
- Esophageal Cancer Research and Treatment
- Cancer Genomics and Diagnostics
- Ocular Diseases and Behçet’s Syndrome
- Species Distribution and Climate Change
- Fish Ecology and Management Studies
- Biliary and Gastrointestinal Fistulas
- Retinal and Optic Conditions
- Pluripotent Stem Cells Research
- Birth, Development, and Health
- Balance, Gait, and Falls Prevention
- Esophageal and GI Pathology
- Traumatic Brain Injury and Neurovascular Disturbances
- Gastroesophageal reflux and treatments
- Angiogenesis and VEGF in Cancer
- Human Resource Development and Performance Evaluation
- Genetic factors in colorectal cancer
University of California, San Francisco
2023-2024
San Francisco General Hospital
2023-2024
Lieber Institute for Brain Development
2024
Pratt Institute
2022
Duke University
2022
University of Michigan
2020-2022
Brown University
2022
Michigan Medicine
2021
Ross School
2015
Los Alamos National Laboratory
2010
Organs are composed of diverse cell types that traverse transient states during organogenesis. To interrogate this diversity human development, we generate a single-cell transcriptome atlas from multiple developing endodermal organs the respiratory and gastrointestinal tract. We illuminate states, transcription factors, organ-specific epithelial stem mesenchyme interactions across lineages. implement as high-dimensional search space to benchmark pluripotent (hPSC)-derived intestinal...
Pluripotent-stem-cell-derived human intestinal organoids (HIOs) model some aspects of development and disease, but current culture methods do not fully recapitulate the diverse cell types complex organization intestine are reliant on 3D extracellular matrix or hydrogel systems, which limit experimental control translational potential for regenerative medicine. We describe suspension as a simple, low-maintenance method culturing HIOs promoting in vitro differentiation an organized serosal...
The human respiratory epithelium is derived from a progenitor cell in the distal buds of developing lung. These "bud tip progenitors" are regulated by reciprocal signaling with surrounding mesenchyme; however, mesenchymal heterogeneity and function lung poorly understood. We interrogated single-cell RNA sequencing data multiple specimens identified population present during development that highly enriched for expression WNT agonist RSPO2, we found adjacent bud progenitors RSPO2 receptor...
Epithelial organoids derived from intestinal tissue, called enteroids, recapitulate many aspects of the organ in vitro and can be used for biological discovery, personalized medicine, drug development. Here, we interrogated cell signaling environment within developing human intestine to identify niche cues that may important epithelial development homeostasis. We identified an EGF family member, EPIREGULIN (EREG), which is robustly expressed crypt. Enteroids generated grown standard culture...
BACKGROUND: Frailty, a decline in physiological reserve, prognosticates poorer outcomes for several neurosurgical conditions. However, the impact of frailty on traumatic brain injury is not well characterized. OBJECTIVE: To analyze association between and intracranial hemorrhage (tICH) nationwide cohort. METHODS: We identified all adult admissions tICH National Trauma Data Bank from 2007 to 2017. Frailty was quantified using validated modified 5-item Index (mFI-5) metric (range = 0-5), with...
Abstract Pathophysiology of many neuropsychiatric disorders, including schizophrenia (SCZD), is linked to habenula (Hb) function. While pharmacotherapies and deep brain stimulation targeting the Hb are emerging as promising therapeutic treatments, little known about cell type-specific transcriptomic organization human or how it altered in SCZD. Here we define molecular neuroanatomy identify changes individuals with SCZD compared neurotypical controls. Utilizing Hb-enriched postmortem tissue,...
NOTCH signaling is a key regulator involved in maintaining intestinal stem cell (ISC) homeostasis and for balancing differentiation. Using single-cell transcriptomics, we observed that OLFM4, target gene present ISCs, first expressed at 13 weeks post-conception the developing human intestine increases over time. This led us to hypothesize requirement acquired across development. To test this, established series of epithelium-only organoids (enteroids) from different developmental stages used...
Wearable technology-based measurement systems hold potential for the therapeutic and rehabilitation management of patients with various chronic diseases. The purpose this study was to assess accuracy test⁻retest reliability a new-generation wearable sensor-based system, dubbed Ambulosono, bio-feedback training. Ambulosono sensor system cross-validated by comparing its functionality iPod touch (4th generation) system. Fifteen participants underwent gait test measure parameters while wearing...
Human intestinal organoids (HIOs) generated from pluripotent stem cells provide extraordinary opportunities to explore development and disease. Here, we generate a single-cell transcriptome reference atlas HIOs multiple developing human organs quantify the specificity of HIO cell fate acquisition, alternative fates. We identify epithelium-mesenchyme interactions, transcriptional regulators involved in specification, maturation features primary tissue that are recapitulated HIOs. use an time...
TP53 mutations underlie Barrett's esophagus (BE) progression to dysplasia and cancer. During BE progression, the ubiquitin ligase (E3) RNF128/GRAIL switches expression from isoform 2 (Iso2) Iso1, stabilizing mutant p53. However, ubiquitin-conjugating enzyme (E2) that partners with Iso1 stabilize p53 is unknown.Single-cell RNA sequencing of paired normal tissues identified candidate E2s, further investigated in data esophageal adenocarcinoma (EAC) samples. Biochemical cellular studies helped...
SUMMARY Mammalian respiratory system development is regulated by complex reciprocal signaling events that take place between epithelial cells and the surrounding mesenchymal cells; however, heterogeneity function in developing human lung poorly understood. We interrogated single cell RNA sequencing data from multiple specimens identified a population present during highly enriched for expression of WNT agonist R-SPONDIN2 ( RSPO2 ), we found adjacent bud tip progenitors are receptor LGR5 . By...
Purpose: Early and intermediate non-neovascular AMD (NN-AMD) has the potential to progress either advanced NN-AMD with geographic atrophy, or neovascular (N-AMD) CNV. This exploratory study performed an unbiased analysis of aqueous humor transcriptome in patients early vs. treatment-naïve N-AMD determine feasibility using this method future studies investigating pathways triggers for conversion from one form another. Methods: Aqueous samples were obtained 20 untreated N-AMD, graded on...
ABSTRACT Many esophageal diseases can arise during development or throughout life. Therefore, well-characterized in vitro models and detailed methods are essential for studying human development, homeostasis disease. Here, we (1) create an atlas of the cell types observed normal adult esophagus; (2) establish ancestrally diverse biobank esophagus tissue to interrogate injury; (3) benchmark using atlas. We created a single-cell RNA sequencing reference fresh biopsies continuously expanding...
To describe an alternate surgical technique for fluocinolone acetonide (Retisert) implantation in patients with extensive pars plana and plicata fibrosis secondary to chronic non-infectious uveitis.
Purpose: Epidemiologically, men have a higher incidence, severity, and progression of diabetic retinopathy (DR) than women. We investigated microvascular differences between women with diabetes on optical coherence tomography angiography (OCTA). Methods: Three × 3 mm OCTA macula scans non-diabetic patients were obtained. Vascular parameters included parafoveal vessel density (VD), length (VLD), flow index (FI) the superficial capillary plexus (SCP) deep (DCP) as well foveal avascular zone...
Summary Epithelial organoids derived from intestinal tissue, also referred to as mini-intestines or mini-guts, recapitulate many aspects of the organ in vitro and can be used for biological discovery, personalized medicine, drug development. Murine represent a homeostatic system that balances stem cell maintenance within crypt-like compartment differentiation villus-like 1–3 . However, this balance spatial organization has not been achieved with human 4 Here, we leverage single RNA-seq data...
SUMMARY Human pluripotent stem cell (hPSC)-derived intestinal organoids (HIOs) generated using directed differentiation lack some cellular populations found in the native organ, including vasculature. Using single RNA sequencing (scRNAseq), we have identified a transient population of endothelial cells (ECs) present early HIO that are lost over time culture. Here, developed method to enhance co-differentiation and maintenance ECs within HIOs (vHIOs). Given known possess organ specific gene...
Exploiting the relationships among data is a classical query optimization technique. As persistent increasingly being created and maintained programmatically, prior work that infers from statistics misses an important opportunity. We present ConstrOpt, first tool identifies by analyzing database-backed applications. Once identified, ConstrOpt leverages constraints to optimize application's physical design execution. Instead of developing fixed set predefined rewriting rules, employs...
Summary European Americans (EA) are more susceptible to esophageal tissue damage and inflammation when exposed gastric acid bile reflux have a higher incidence of adenocarcinoma compared African (AA). Population studies implicated specific genes for these differences; however, the underlying cause differences is not well understood. We describe robust long-term culture system grow primary human esophagus in vitro , use single cell RNA sequencing compare biopsies their counterparts, identify...
A 71 year-old male presented to the hospital with a one day history of left lower abdominal pain and bright red blood per rectum. He had fifty-year smokeless tobacco use no prior colonoscopy. Physical exam revealed an afebrile man stable vital signs mild tenderness in quadrant. Computed tomography abdomen pelvis uncomplicated sigmoid diverticulitis. His course was complicated drop hemoglobin from 12.7 gm/dL 7.6 resulting two units packed cells. Following transfusion his improved symptoms...