A5003028827- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Neuroscience of respiration and sleep
- Digestive system and related health
- Single-cell and spatial transcriptomics
- Immunotherapy and Immune Responses
- Lung Cancer Treatments and Mutations
- Organ Transplantation Techniques and Outcomes
- Diabetes and associated disorders
- Transplantation: Methods and Outcomes
- Renal and related cancers
- Birth, Development, and Health
- High Altitude and Hypoxia
- Colorectal Cancer Treatments and Studies
- Cystic Fibrosis Research Advances
- Cancer and Skin Lesions
- Helicobacter pylori-related gastroenterology studies
- Acute Lymphoblastic Leukemia research
- Genetic and Kidney Cyst Diseases
- Maternal and fetal healthcare
- RNA modifications and cancer
- Renal Transplantation Outcomes and Treatments
- Childhood Cancer Survivors' Quality of Life
- Esophageal and GI Pathology
- Liver Disease and Transplantation
University of California, San Francisco
2017-2024
University of Louisville
2022
Universidad Católica de Santa Fe
2022
Beth Israel Deaconess Hospital
1997
Harvard University Press
1997
The autoimmune regulator (Aire), a well-defined transcriptional in the thymus, is also found extrathymic Aire-expressing cells (eTACs) secondary lymphoid organs. eTACs are hematopoietic antigen-presenting and inducers of immune tolerance, but their precise identity has remained unclear. Here, we use single-cell multiomics, transgenic murine models, functional approaches to define at transcriptional, genomic, proteomic level. We find that consist two similar cell types: CCR7+ migratory...
Naturally occurring cases of monogenic type 1 diabetes (T1D) help establish direct mechanisms driving this complex autoimmune disease. A recently identified de novo germline gain-of-function (GOF) mutation in the transcriptional regulator STAT3 was found to cause neonatal T1D. We engineered a novel knock-in mouse incorporating highly diabetogenic human (K392R) and that these mice recapitulated phenotype. Paired single-cell TCR RNA sequencing revealed STAT3-GOF drives proliferation clonal...
The gastrointestinal tract relies on the production, maturation, and transit of mucin to protect against pathogens lubricate epithelial lining. Although molecular cellular mechanisms that regulate production movement are beginning be understood, upstream signals contribute regulation remain unclear. Here, we report inflammatory cytokine tumor necrosis factor (TNF), generated by epithelium, contributes homeostasis regulating both cell differentiation cystic fibrosis transmembrane conductance...
Background: Lateral abdominal wall defects are a significant contributor to patient morbidity and mortality in the United States. Reconstruction involving flank hernias bulges is relatively scarce literature despite its serious consequences. The authors aim identify an objective approach for evaluation successful repair of lateral wall. Methods: A retrospective analysis was carried out on patients presenting open defect performed by single surgeon. Over 5-year period, there were 29...
Kidney disease is highly heritable; however, the causal genetic variants, cell types in which these variants function, and molecular mechanisms underlying kidney remain largely unknown. To identify loci affecting we performed a GWAS using multiple function biomarkers identified 462 loci. begin to investigate how affect generated single-cell chromatin accessibility (scATAC-seq) maps of human candidate
Background Donation after circulatory death (DCD) liver allografts are associated with higher rates of primary non-function (PNF) and ischemic cholangiopathy (IC). Advanced recovery techniques, including thoracoabdominal normothermic regional perfusion (TA-NRP), may improve organ utilization patient allograft outcomes. Given the increasing US experience TA-NRP DCD recovery, we evaluated outcomes transplanted TA-NRP. Methods Liver from donors were identified 5/1/2021 to 1/31/2022 across 8...
Mammalian carotid body arterial chemoreceptors function as an early warning system for hypoxia, triggering acute life-saving arousal and cardiorespiratory reflexes. To serve this role, glomus cells are highly sensitive to decreases in oxygen availability. While the mitochondria plasma membrane signaling proteins have been implicated sensing by cells, mechanism underlying their mitochondrial sensitivity hypoxia compared other is unknown. Here, we identify HIGD1C, a novel hypoxia-inducible...
Abstract A key aspect of nutrient absorption is the exquisite division labor across length small intestine, with individual classes micronutrients taken up at different positions. For millennia, intestine was thought to comprise three segments indefinite borders: duodenum, jejunum, and ileum. By examining fine-scale longitudinal segmentation mouse human intestines, we identified transcriptional signatures upstream regulatory factors that define five domains absorption, distinct from...
Mutations in the gene encoding zinc-finger transcription factor Ikaros (
Abstract T lymphocytes normally express their Ag receptors in association with the CD3 proteins, which include CD3zeta. In CD3zeta eta(null) mice thymic and peripheral do not TCR/CD3 complex on surface due to retention endoplasmic reticulum of remaining polypeptide chains. However, intestinal intraepithelial (iIEL) TCR, because Fc epsilonRI gamma chain replaced complex. Here we report that a subset CD8alpha alpha+ iIEL presence could be accounted for by expression gammaRIII(CD16) Because...
Abstract The carotid body (CB) is the major chemoreceptor for blood oxygen in control of ventilation mammals, contributing to physiological adaptation high altitude, pregnancy, and exercise, its hyperactivity linked chronic conditions such as sleep-disorder breathing, hypertension, heart failure, airway constriction, metabolic syndrome ( 1–3 ). Upon acute hypoxia (PO 2 =100 mmHg <80 mmHg), K + channels on CB glomus cells are inhibited, causing membrane depolarization trigger Ca +2 influx...
Abstract Naturally occurring cases of monogenic type 1 diabetes (T1D) provide rare opportunities to establish direct mechanisms that cause this complex autoimmune disease. A recently identified de novo germline gain-of-function (GOF) mutation in the transcriptional regulator signal transducer and activator transcription 3 (STAT3) was shown neonatal T1D at birth. To investigate role STAT3 hyperactivity T1D, we engineered a novel knock-in (KI) mouse incorporating highly diabetogenic human...
There remains a critical need for improved staging of non-small-cell lung cancer, as recurrence and mortality due to undetectable metastases at the time surgery remain high even after complete resection tumors currently categorized 'early stage.' A 14-gene quantitative PCR-based expression profile has been extensively validated better identify patients high-risk 5-year surgical than conventional - that almost always results from previously metastases. Furthermore, prospective studies now...
Abstract The autoimmune regulator (Aire) protein, a key transcriptional expressed in medullary thymic epithelial cells (mTECs), is crucial for central tolerance. Aire also found extrathymic Aire-expressing (eTACs) secondary lymphoid organs. eTACs are hematopoietic antigen-presenting that capable of inducing immune tolerance, but the precise identity has remained unclear. To define eTACs, we utilized combination single-cell multiomics, transgenic murine models, and functional approaches. We...
Abstract The Autoimmune Regulator ( Aire ) gene, well defined for its role in medullary thymic epithelial cells (mTECs) and immune self-tolerance, is also expressed extrathymic -expressing (eTACs) the secondary lymphoid organs. eTACs have been shown to be hematopoietic antigen presenting (APCs) potent inducers of tolerance (1–3). However, precise identity function these remain unclear. Here, we use high-dimensional single-cell multiomics functional approaches define at transcriptional,...