A5079961169- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Hematopoietic Stem Cell Transplantation
- Fibroblast Growth Factor Research
- Bone Metabolism and Diseases
- Cancer, Hypoxia, and Metabolism
- Immune cells in cancer
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Immunotherapy and Immune Responses
- TGF-β signaling in diseases
- Bone health and treatments
- Developmental Biology and Gene Regulation
- Liver physiology and pathology
- Cancer-related gene regulation
- Acute Myeloid Leukemia Research
- Wnt/β-catenin signaling in development and cancer
- Immune Response and Inflammation
- Pluripotent Stem Cells Research
- Neonatal Respiratory Health Research
- Hematological disorders and diagnostics
- IL-33, ST2, and ILC Pathways
- Xenotransplantation and immune response
- Chemokine receptors and signaling
- Immune responses and vaccinations
- Diabetes and associated disorders
University of California, Merced
2014-2024
Quantitative BioSciences
2012
University of California, Berkeley
2004-2005
Massachusetts General Hospital
1998-2003
Harvard University
1998-2003
National Marrow Donor Program
1999
U.S. National Science Foundation
1998
Fringe O-fucose-beta1,3-N-acetylglucosaminyltransferases modulate Notch signaling by potentiating induced Delta-like ligands, while inhibiting Serrate/Jagged1 ligands. Based on binding studies, the differential effects of Drosophila fringe (DFng) are thought to result from alterations in glycosylation that enhance Delta but reduce Serrate binding. Here, we report expression mammalian proteins (Lunatic [LFng], Manic [MFng], or Radical [RFng] Fringe) increased Delta1 and activation Notch1 293T...
Mixed hematopoietic chimerism induced with a nonmyeloablative conditioning regimen leads to donor-specific transplantation tolerance. Analyses of specific Vbeta-bearing T-cell families that recognize endogenous superantigens demonstrated tolerance is due mainly an intrathymic deletional mechanism in these mixed chimeras. However, are not known behave as classical antigens. We therefore used receptor (TCR) transgenic (Tg) recipients expressing clonotypic TCR for allogeneic major...
Abstract Increased osteoblast activity in sclerostin-knockout (Sost−/−) mice results generalized hyperostosis and bones with small bone marrow cavities resulting from hyperactive mineralizing populations. Hematopoietic cell fate decisions are dependent on their local microenvironment, which contains stromal populations that support both hematopoietic stem quiescence facilitate B-cell development. In this study, we investigated whether high mass environments affect development via the...
Sclerostin (Sost) is a negative regulator of bone formation and blocking its function via antibodies has shown great therapeutic promise by increasing both mass in humans animal models. deletion Sost KO mice (Sost-/- ) causes high (HBM) similar to sclerosteosis patients. Sost-/- have been display an up 300% increase volume/total volume (BV/TV), relative age-matched controls. It postulated that the main source skeletal sclerostin osteocyte. To understand cell-type specific contributions HBM...
Loss of Sostdc1, a growth factor paralogous to Sost, causes the formation ectopic incisors, fused molars, abnormal hair follicles, and resistance kidney disease. Sostdc1 is expressed in periosteum, source osteoblasts, fibroblasts mesenchymal progenitor cells, which are critically important for fracture repair. Here, we investigated role bone metabolism Mice lacking (Sostdc1(-/-)) had low mass phenotype associated with loss trabecular both lumbar vertebrae appendicular skeleton. In contrast,...
Abstract Alterations in inhibitory receptor expression on NK cells have been detected mixed allogeneic chimeras and mosaic MHC class I-expressing transgenic mice. However, it is not known whether or are tolerant to host donor Ags chimeras. In vitro studies shown a lack of mutual tolerance separated obtained from Using BALB/c→B6 fully MHC-mismatched chimeras, we now investigated this question vivo. Neither nor showed evidence for activation, as indicated by B220 Thy-1.2 chimeric mice at...
Embryoid body (EB) formation closely recapitulates early embryonic development with respect to lineage commitment. Because it is greatly affected by cell-cell and cell-substrate interactions, the ability control initial number of cells in aggregates provide an appropriate substrate are crucial parameters for uniform EB formation. Here we report ultra-rapid fabrication culture method utilizing a laser-jet printer generate arrayed honeycomb microwells tunable sizes induction EBs from single...
Ly-49 molecules are used by NK cells to distinguish 'self' from 'non-self', but the determinants of expression that allow this distinction be made not understood. The education for self/non-self recognition was studied in murine mixed allogeneic bone marrow chimeras, which both host and donor origin. Marked alterations receptor were observed on developing BALB/c --> B6 chimeras. Ly-49A Ly-49G2 lower chimeras compared non-transplanted controls. Among cells, Ly-49C levels reduced, proportion...
Romosozumab, a humanized monoclonal antibody specific for sclerostin (SOST), has been approved treatment of postmenopausal women with osteoporosis at high risk fracture. Previous work in global knockout (Sost-/-) mice indicated alterations immune cell development the bone marrow (BM), which could be possible side effect romosozumab-treated patients. Here, we examined effects short-term depletion BM on hematopoiesis young receiving (Scl-Ab) 6 weeks, and long-term Sost deficiency wild-type...
Abstract Although Notch plays a crucial role in T cell development, regulation of signaling the thymus is not well understood. Kuzbanian, an ADAM protease, has been implicated cleavage both receptors and ligand, Delta. In this study we show that expression dominant-negative form Kuzbanian (dnKuz) leads to reduced TCRβ double-negative thymocytes partial block between double-positive stages development. These defects were rescued by overexpression Delta-1 on thymocytes. Mixed chimeras showed...
NK cells are innate-like lymphocytes that eliminate virally infected and cancerous cells, but the mechanisms control cell development cytotoxicity incompletely understood. We identified roles for sclerostin domain-containing-1 (Sostdc1) in function. Sostdc1-knockout (Sostdc1-/-) mice display a progressive accumulation of transitional (tNKs) (CD27+CD11b+) with age, indicating partial developmental block. The Ly49 repertoire Sostdc1-/- is also changed. Lower frequencies splenic tNKs express...
The contributions of skeletal cells to the processes B cell development in bone marrow (BM) have not been completely described. von-Hippel Lindau protein (VHL) plays a key role cellular responses hypoxia. Previous work showed that Dmp1-Cre;Vhl conditional knockout mice (VhlcKO), which deletes Vhl subsets mesenchymal stem cells, late osteoblasts and osteocytes, display dysregulated growth reduction cells. Here, we investigated mechanisms underlying defects using flow cytometry high-resolution...
Ly-49 receptor expression was studied in NK cells that developed fully MHC-mismatched mixed bone marrow chimeras, which host and donor MHC ligands were expressed solely on various proportions of hemopoietic or both nonhemopoietic cells. When the only source ligand, a strong correlation between level down-regulation Ly-49A, Ly-49C, Ly-49G2 number expressing their observed In some animals with low levels chimerism, origin receptors at higher than normal mice same strain. This unexpected...
Understanding how embryonic stem cells and their derivatives interact with the adult host immune system is critical to developing therapeutic potential. Murine cell-derived hematopoietic progenitors (ESHPs) were generated via coculture bone marrow stromal cell line, OP9, then transplanted into NOD.SCID.Common Gamma Chain (NSG) knockout mice, which lack B, T, natural killer cells. Compared control mice lineage-negative (Lin − BM) progenitors, ESHP-transplanted attained a low but significant...
Abstract Previous studies of NK cell inhibitory Ly-49 genes showed their expression is stochastic. However, relatively few have examined the mechanisms governing acquisition receptors in conjunction with activating and development. We hypothesized that surface nonrandom influenced by receptors. analyzed “clusters” defined combinatorial (Ly-49H Ly-49D) (Ly-49I Ly-49G2) C57BL/6 mice. Using product rule to evaluate interdependencies receptors, we found evidence for a tightly regulated at...