A5076251598- Immune Cell Function and Interaction
- IL-33, ST2, and ILC Pathways
- Neonatal Respiratory Health Research
- Immune cells in cancer
- T-cell and B-cell Immunology
- Platelet Disorders and Treatments
- Hematopoietic Stem Cell Transplantation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Mitochondrial Function and Pathology
- RNA modifications and cancer
- Immune Response and Inflammation
- Epigenetics and DNA Methylation
- Neurological disorders and treatments
- Genetic Neurodegenerative Diseases
- Biomedical and Engineering Education
- Experimental Learning in Engineering
- Genetics, Bioinformatics, and Biomedical Research
- Cancer-related molecular mechanisms research
- Acute Myeloid Leukemia Research
- Eosinophilic Esophagitis
- Helicobacter pylori-related gastroenterology studies
- Galectins and Cancer Biology
- Chronic Myeloid Leukemia Treatments
- CAR-T cell therapy research
- Birth, Development, and Health
University of California, Santa Cruz
2018-2025
Duke Medical Center
2014-2020
Duke University
2014-2020
Duke University Hospital
2014-2020
StemCells (United States)
2018
Platelet dysregulation is drastically increased with advanced age and contributes to making cardiovascular disorders the leading cause of death elderly humans. Here, we reveal a direct differentiation pathway from hematopoietic stem cells into platelets that progressively propagated upon aging. Remarkably, aging-enriched platelet path decoupled all other lineages, including erythropoiesis, operates as an additional layer in parallel canonical production. This results two molecularly...
Huntington9s disease (HD) is a neurodegenerative caused by the expansion of poly-glutamine (poly-Q) stretch in huntingtin (Htt) protein. Gain-of-function effects mutant Htt have been extensively investigated as major driver neurodegeneration HD. However, loss-of-function poly-Q mutations recently emerged potential drivers pathophysiology. Early synaptic problems excitatory cortical and striatal connections reported HD, but role protein connectivity was unknown. Therefore, we <i>in vivo</i>...
ABSTRACT The discovery of a fetal origin for tissue-resident macrophages (trMacs) has inspired an intense search the mechanisms underlying their development. Here, we performed in vivo lineage tracing cells with expression history IL7Rα, marker exclusively associated lymphoid adult hematopoiesis. Surprisingly, found that Il7r-Cre labeled fetal-derived, trMacs. Labeling was almost complete some tissues and partial others. putative progenitors trMacs, yolk sac (YS) erythromyeloid progenitors,...
Huntington's disease (HD) is caused by an autosomal dominant polyglutamine expansion mutation of Huntingtin (HTT). HD patients suffer from progressive motor, cognitive, and psychiatric impairments, along with significant degeneration the striatal projection neurons (SPNs) striatum. widely accepted to be a toxic gain-of-function mutant HTT. However, whether loss HTT function, because dominant-negative effects protein, plays role in required for SPN health function are not known. Here, we...
Age-related morbidity is associated with a decline in hematopoietic stem cell (HSC) function, but the mechanisms of HSC aging remain unclear. We performed heterochronic transplants followed by quantitative analysis reconstitution. Although young HSCs outperformed old recipients, unexpectedly failed to outcompete aged recipients. Interestingly, despite substantial enrichment megakaryocyte progenitors (MkPs) mice situ and reported platelet (Plt) priming age, transplanted were deficient...
Project-based learning (PBL) has long been recognized as an effective way to teach complex biology concepts. However, not all institutions have the resources facilitate project-based coursework for students. We developed a framework facilitating PBL using remote-controlled internet-connected microscopes. Through this approach, one lab facility can host experiment many students around world simultaneously. Experiments on platform be run timescales and with materials that are typically...
Abstract Epigenetic mechanisms regulate the multilineage differentiation capacity of hematopoietic stem cells (HSCs) into a variety blood and immune cells. Mapping chromatin dynamics functionally defined cell populations will shed mechanistic insight 2 major, unanswered questions in biology: how does epigenetic identity contribute to type’s lineage potential, do cascades remodeling dictate ensuing fate decisions? Our recent work revealed evidence gene priming HSCs, where open cis-regulatory...
Tobacco use during pregnancy has many deleterious health consequences for not only the smoking mother, but also on unborn fetus. Children of mothers are reported to have higher frequency and severity respiratory diseases later in life; however, mechanisms driving this increased vulnerability clearly understood. One potential cause disease susceptibility is an altered immune system, originating epigenetically maladaptive hematopoietic stem cells (HSCs). Here, we show that perinatal nicotine...
Our respiratory system is vital to protect us from the surrounding nonsterile environment; therefore, it critical for a state of homeostasis be maintained through balance inflammatory cues. Recent studies have shown that actively transcribed noncoding regions genome are emerging as key regulators biological processes, including inflammation.
ABSTRACT Tissue-resident lymphoid cells (TLCs) span the spectrum of innate-to-adaptive immune function. Unlike traditional, circulating lymphocytes that are continuously generated from hematopoietic stem (HSCs), many TLCs fetal origin and poorly adult HSCs. Here, we sought to further understand murine TLC development roles Flk2 IL7Rα, two cytokine receptors with known function in traditional lymphopoiesis. Using Flk2- Il7r-Cre lineage tracing, found peritoneal B1a cells, splenic marginal...
SUMMARY Platelet dysregulation is drastically increased with advanced age and contributes to making cardiovascular disorders the leading cause of death elderly humans. Hematopoietic stem progenitor cells continuously give rise platelets, but their contributions variable platelet production activity throughout life remain unclear. Here we reveal a direct differentiation pathway from hematopoietic into platelets that unique aging. An unequivocal genetic lineage tracing mouse model demonstrated...
Abstract Project-based learning (PBL) has long been recognized as an effective way to teach complex biology concepts. However, not all institutions have the resources facilitate project-based coursework for students. We developed a framework facilitating PBL using remote-controlled internet-connected microscopes. Through this approach, one lab facility can host experiment allowing simultaneous interaction by many students worldwide. Experiments on platform be run timescales and with...
Abstract Respiratory diseases are a leading cause of death worldwide, with highly varied vulnerability to disease between individuals. The underlying reasons susceptibility unknown, but often include variable immune response in lungs. Recently, we identified surprising novel role the interleukin 7 receptor (IL7R), primarily lymphoid-associated regulator, fetal-specified, lung-resident macrophage development. Here, report that traditional, hematopoietic stem cell-derived myeloid cells adult...
Abstract The discovery of a fetal origin for tissue-resident macrophages (trMacs) has inspired an intense search the mechanisms underlying their development. Here, we performed in vivo lineage tracing cells with expression history IL-7Rα, marker exclusively associated lymphoid adult hematopoiesis. Surprisingly, found that IL7R-Cre labeled fetal-derived, trMacs. Labeling was almost complete some tissues and partial other organs. putative progenitors trMacs, yolk sac (YS) erythromyeloid...
Helicobacter pylori colonizes half of the world's population and is responsible for a significant disease burden by causing gastritis, peptic ulcers, gastric cancer. The development host inflammation drives these diseases, but there are still open questions in field about how H. controls this process. We characterized using an 8-month mouse infection time course comparison wild type (WT) previously identified mutant lacking TlpA chemoreceptor that causes elevated inflammation. Our work shows...
Abstract The respiratory system exists at the interface between our body and surrounding non-sterile environment; therefore, it is critical for a state of homeostasis to be maintained through balance pro- anti- inflammatory cues. An appropriate response vital combating pathogens, while an excessive or uncontrolled can lead development chronic diseases. Recent studies show that actively transcribed noncoding regions genome are emerging as key regulators biological processes, including...
Abstract Tissue-resident macrophages (TRMs) play critical roles in tissue homeostasis and disease. Many populations of TRMs derive from fetal progenitors independently self-maintain across the lifespan through situ proliferation. Here, we have identified interleukin-7 receptor (IL7R) as a novel regulator TRM development. Using an IL7R-Cre lineage tracing model, observed that adult brain, epidermis, liver, lung were highly labeled by IL7R-cre, absence IL7Ra mRNA or protein expression. To gain...
Abstract Helicobacter pylori colonizes half of the world’s population and is responsible for a significant disease burden by causing gastritis, peptic ulcers, gastric cancer. The development host inflammation drives these diseases, but there are still open questions in field about how H. controls this process. We characterized using an eight month mouse infection time course comparison wild type previously identified mutant lacking TlpA chemoreceptor that causes elevated inflammation. Our...