A5004111575- Hematopoietic Stem Cell Transplantation
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Pluripotent Stem Cells Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Zebrafish Biomedical Research Applications
- Immune cells in cancer
- CRISPR and Genetic Engineering
- Barrier Structure and Function Studies
- Complement system in diseases
- Renal and related cancers
- CAR-T cell therapy research
- Virus-based gene therapy research
- Mesenchymal stem cell research
- Epigenetics and DNA Methylation
- Single-cell and spatial transcriptomics
- Immune Response and Inflammation
- Alzheimer's disease research and treatments
- Neonatal Respiratory Health Research
- Photochromic and Fluorescence Chemistry
- Platelet Disorders and Treatments
- bioluminescence and chemiluminescence research
- Renal Diseases and Glomerulopathies
- Prenatal Screening and Diagnostics
- Phagocytosis and Immune Regulation
University of California, Irvine
2015-2025
University of California System
2021
Stanford University
2007-2018
Institute for Stem Cell Biology and Regenerative Medicine
2011-2018
UC Irvine Health
2016
California Institute for Regenerative Medicine
2010-2014
Irvine Valley College
2014
Icahn School of Medicine at Mount Sinai
2010
Stanford Medicine
2009
University of California, San Diego
2002-2006
Mobilization of the T-cell response against cancer has potential to achieve long-lasting cures. However, it is not known how harness antigen-presenting cells optimally an effective antitumor response. In this study, we show that anti-CD47 antibody–mediated phagocytosis by macrophages can initiate immune Using ovalbumin model antigen system, resulted in increased priming OT-I T [cluster differentiation 8-positive (CD8 + )] but decreased OT-II (CD4 ). The CD4 was characterized a reduction...
The innate immune system is strongly implicated in the pathogenesis of Alzheimer's disease (AD). In contrast, role adaptive immunity AD remains largely unknown. However, numerous clinical trials are testing vaccination strategies for AD, suggesting that T and B cells play a pivotal this disease. To test hypothesis influences pathogenesis, we generated an immune-deficient mouse model lacks T, B, natural killer (NK) cells. resulting "Rag-5xfAD" mice exhibit greater than twofold increase...
Common lymphoid progenitors (CLPs) clonally produce both B- and T-cell lineages, but have little myeloid potential in vivo. However, some studies claim that the upstream lymphoid-primed multipotent progenitor (LMPP) is thymic seeding population, suggest CLPs are primarily B-cell-restricted. To identify surface proteins distinguish functional from B-cell progenitors, we used a new computational method of Mining Developmentally Regulated Genes (MiDReG). We identified Ly6d, which divides into...
Gene expression profiling using microarrays has been limited to comparisons of gene between small numbers samples within individual experiments. However, the unknown and variable sensitivities each probeset have rendered absolute any given nearly impossible estimate. We overcome this limitation by a very large number (>10,000) varied microarray data as common reference, so that statistical attributes probeset, such dynamic range threshold low high expression, can be reliably discovered...
Abstract Gene correction in human long-term hematopoietic stem cells (LT-HSCs) could be an effective therapy for monogenic diseases of the blood and immune system. Here we describe approach X-linked sSevere cCombined iImmunodeficiency (SCID-X1) using targeted integration a cDNA into endogenous start codon to functionally correct disease-causing mutations throughout gene. Using CRISPR-Cas9/AAV6 based strategy, achieve up 20% frequencies LT-HSCs. As measures lack toxicity observe no evidence...
Hematopoiesis is a tightly controlled process maintained by small pool of hematopoietic stem cells (HSCs). Here, we demonstrate that the LT-HSC, MPP, premegakaryocytic/erythroid, Pre CFU-E, GM, MkP, and granulocyte-macrophage compartments were all significantly reduced in E2A-deficient bone marrow. Despite severe depletion erythroid progenitors, erythrocyte megakaryocyte equivalent marrow as compared with wild-type mice. HSCs also failed to efficiently maintain HSC on serial transplantation,...
Highlights•Mesoderm and neural crest-derived pericytes (PCs) from hPSCs termed mPCs ncPCs•mPCs ncPCs express general brain-specific pericyte genes•mPCs associate with promote barrier properties of endothelial cells•WNT is important, but not necessary for PC specificationSummaryIn the CNS, perivascular cells ("pericytes") to mediate formation tight junctions essential function blood-brain (BBB). The BBB protects CNS by regulating flow nutrients toxins into out brain. dysfunction has been...
The contribution of the different waves and sites developmental hematopoiesis to fetal adult blood production remains unclear. Here, we identify lymphatic vessel endothelial hyaluronan receptor-1 (LYVE1) as a marker yolk sac (YS) endothelium definitive hematopoietic stem progenitor cells (HSPCs). Endothelium in mid-gestation YS vitelline vessels, but not dorsal aorta placenta, were labeled by Lyve1-Cre. Most HSPCs erythro-myeloid progenitors Lyve1-Cre lineage traced, primitive erythroid not,...
The promise of pluripotent stem cells as a research and therapeutic tool is partly undermined by the technical challenges generating maintaining these in culture. Human embryonic (hESCs) are exquisitely sensitive to culture conditions, require constant signaling growth factors cell–cell cell–matrix interactions prevent apoptosis, senescence, differentiation. Previous work from our laboratory demonstrated that overexpression prosurvival gene BCL2 mouse overrode requirement serum feeder...
A goal of regenerative medicine is to identify cardiovascular progenitors from human ES cells (hESCs) that can functionally integrate into the heart. Previous studies evaluate developmental potential candidate hESC-derived have delivered these murine and porcine cardiac tissue, with inconclusive evidence regarding capacity physiologically engraft in xenotransplantation assays. Further, lineage couple myocardium remains untested unknown. Here, we prospectively identified a population ROR2 +...
Hematopoiesis in the embryo proceeds a series of waves, with primitive erythroid-biased waves succeeded by definitive within which properties hematopoietic stem cells (multilineage potential, self-renewal, and engraftability) gradually arise. Whereas self-renewal engraftability have previously been examined embryo, multipotency has not thoroughly addressed, especially at single-cell level or well-defined populations. To identify when where clonal multilineage potential arises during...
The factors that regulate the rate of production T cells by thymus remain incompletely defined. To test whether generation functional cell receptors limits thymic export, we made use a line mice, LN3alphabeta, have endogenously prerearranged TCR genes. genes were expressed abnormally early in hemopoietic development, indicating RAG-mediated recombination, rather than transcription factor expression, is key determinant initiation robust transcription. Thymic export rates similar between...
We present a method termed mining developmentally regulated genes (MiDReG) to predict whose expression is either activated or repressed as precursor cells differentiate. MiDReG does not require gene data from intermediate stages of development. based on the patterns between initial and terminal differentiation pathway, coupled with “if-then” rules (Boolean implications) mined large-scale microarray databases. uses two expression-based seed conditions that mark given pathway combines...
Microglia, the brain’s resident myeloid cells, play central roles in brain defense, homeostasis, and disease. Using a prolonged colony-stimulating factor 1 receptor inhibitor (CSF1Ri) approach, we report an unprecedented level of microglial depletion establish model system that achieves empty niche adult brain. We identify cell migrates from subventricular zone associated white matter areas. Following CSF1Ri, these amoeboid cells migrate radially tangentially dynamic wave filling distinct...
Microglia are the primary resident myeloid cells of brain responsible for maintaining homeostasis and protecting central nervous system (CNS) from damage infection. Monocytes monocyte-derived macrophages arising periphery have also been implicated in CNS pathologies, however, distinguishing between different cell populations has difficult. Here, we set out to develop a reliable histological marker that can assess distinct heterogeneity functional contributions, particularly context disease...
The immunoglobulin κ light chain intronic enhancer (iEκ) activates rearrangement and is required to maintain the earlier or more efficient of versus lambda (λ). To understand mechanism how iEκ regulates rearrangement, we employed homologous recombination mutate individual functional motifs within in endogenous locus, including NF-κB binding site (κB), as well κE1, κE2, κE3 E boxes. Analysis impacts these mutations revealed that κE2 a lesser extent but not κE3, were important for activating...
We report the design of a water-soluble, quaternized tamoxifen photoprobe and demonstrate its application in light-controlled induction green fluorescent protein expression via Cre-ER recombinase system.
The tamoxifen inducible Cre-ER/loxP system provides tissue specific temporal control of gene recombination events, and can be used to induce expression reporter genes (e.g. GFP, LacZ) for lineage tracing studies. Cre enzyme fused with estrogen receptor (Cre-ER) is released upon binding, resulting in permanent activation within cells their progeny. Tamoxifen its active metabolite, hydroxytamoxifen (4OHT) diffuses rapidly vivo, making it difficult restrict labeling locations. In this study, we...
Abstract Alzheimer's disease (AD) is the leading cause of age‐related neurodegeneration and characterized neuropathologically by accumulation insoluble beta‐amyloid (Aβ) peptides. In AD brains, plaque‐associated myeloid (PAM) cells cluster around Aβ plaques but fail to effectively clear phagocytosis. PAM were originally thought be brain‐resident microglia. However, several studies have also suggested that Aβ‐induced inflammation causes peripheral monocytes enter otherwise immune‐privileged...