A5050904625- Hematopoietic Stem Cell Transplantation
- CAR-T cell therapy research
- Mesenchymal stem cell research
- Nitric Oxide and Endothelin Effects
- Pluripotent Stem Cells Research
- Renin-Angiotensin System Studies
- Renal Transplantation Outcomes and Treatments
- Acute Myeloid Leukemia Research
- Oral and gingival health research
- Immune Cell Function and Interaction
- Histone Deacetylase Inhibitors Research
- Chronic Myeloid Leukemia Treatments
- Phagocytosis and Immune Regulation
- Tissue Engineering and Regenerative Medicine
- Pharmacological Effects and Toxicity Studies
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- T-cell and B-cell Immunology
- Acute Lymphoblastic Leukemia research
- Hemoglobinopathies and Related Disorders
- Chemotherapy-induced organ toxicity mitigation
- Intestinal and Peritoneal Adhesions
- Orthopaedic implants and arthroplasty
- Biological Research and Disease Studies
- Omental and Epiploic Conditions
- Complement system in diseases
Menlo School
2020-2025
Institute for Stem Cell Biology and Regenerative Medicine
2013-2019
Stanford University
2013-2018
California Institute for Regenerative Medicine
2016
University of California, San Francisco
2016
University of California, Berkeley
2007-2012
QB3
2012
Lawrence Berkeley National Laboratory
2012
Institute of Molecular and Cell Biology
2007
Significance Microglia are the tissue resident macrophages of brain and spinal cord, implicated in important developmental, homeostatic, disease processes, although our understanding their roles is complicated by an inability to distinguish microglia from related cell types. Although they share many features with other macrophages, have distinct developmental origins functions. Here we validate a stable robustly expressed microglial marker for both mouse human, transmembrane protein 119...
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...
CD47 is an antiphagocytic signal that cancer cells employ to inhibit macrophage-mediated destruction. Here, we modified the binding domain of human SIRPα, receptor for CD47, use as a antagonist. We engineered high-affinity SIRPα variants with about 50,000-fold increased affinity relative wild-type SIRPα. As monomers, they potently antagonized on but did not induce macrophage phagocytosis their own. Instead, exhibited remarkable synergy all tumor-specific monoclonal antibodies tested by...
S-nitrosation is a posttranslational, oxidative addition of NO to cysteine residues proteins that has been proposed as cGMP-independent signaling pathway [Hess DT, Matsumoto A, Kim SO, Marshall HE, Stamler JS (2005) Nat Rev Mol Cell Biol 6:150-166]. A paradox only small set reactive cysteines are modified in vivo despite the promiscuous reactivity exhibits with thiols, precluding reaction free primary mechanism S-nitrosation. Here we show specific transnitrosation between procaspase-3 and...
Nitric oxide (NO) regulates a number of essential physiological processes by activating soluble guanylate cyclase (sGC) to produce the second messenger cGMP. The mechanism NO sensing was previously thought result exclusively from binding sGC heme; however, recent studies indicate that heme-bound only partially activates and additional is involved in maximal activation. Furthermore, thiol oxidation cysteines results loss enzyme activity. Herein role NO-stimulated activity investigated. We...
Peritoneal adhesions are fibrous tissues that tether organs to one another or the peritoneal wall and a major cause of postsurgical infectious morbidity. The primary molecular chain events leading initiation has been elusive, chiefly due lack an identifiable cell origin. Using clonal analysis lineage tracing, we have identified injured surface mesothelium expressing podoplanin (PDPN) mesothelin (MSLN) as instigator after surgery in mice. We demonstrate anti-MSLN antibody diminished adhesion...
Nitric oxide (NO) signaling regulates key processes in cardiovascular physiology, specifically vasodilation, platelet aggregation, and leukocyte rolling. Soluble guanylate cyclase (sGC), the mammalian NO sensor, transduces an signal into classical second messenger cyclic GMP (cGMP). binds to ferrous (Fe(2+)) oxidation state of sGC heme cofactor stimulates formation cGMP several hundred-fold. Oxidation ferric (Fe(3+)) desensitizes enzyme NO. The heme-oxidized has emerged as a potential...
Generalized methods for understanding the cell biology of non-model species are quite rare, yet very much needed. In order to address this issue, we have modified a technique traditionally used in biomedical field ecological and evolutionary research. Fluorescent activated sorting (FACS) is often identifying populations. study, developed method identify isolate different populations corals other cnidarians. Using fluorescence-activated (FACS), coral suspension were sorted into cellular using...
Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy limited by graft-versus-host disease (GVHD). In preclinical studies and early-phase clinical enrichment of donor regulatory T cells (Tregs) appears to prevent GVHD promote healthy immunity.We enrolled 44 patients on an open-label, single-center, phase 2 efficacy study investigating if precision selected highly purified Treg manufactured from mobilized peripheral blood improves one-year GVHD-free relapse free survival...
Key Points Upon injury, the mesothelium recruits neutrophils to peritoneal space, which contributes adhesion formation. Neutrophil recruitment and macrophage-depletion kinetics in adhesions differ from normal innate response.
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.
Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for hematological malignancies which graft-versus-host disease (GVHD) remains major complication. The use of donor T-regulatory cells (Tregs) to prevent GVHD appears promising, including in our previous evaluation an engineered graft product (T-reg graft) consisting the timed, sequential infusion CD34+ stem and high-purity Tregs followed by conventional T cells. However, whether immunosuppressive prophylaxis can be...
Nitric oxide (NO), the product of nitric synthase (NOS) reaction, was previously shown to result in S-nitrosation NOS Zn(2+)-tetrathiolate and inactivation enzyme. To probe potential physiological significance S-nitrosation, we determined time scale inducible isoform (iNOS) found it directly correlates with an increase level iNOS S-nitrosation. A kinetic model which arginine is treated as a suicide substrate developed. In this model, NO synthesized at heme cofactor partitioned between...
Soluble guanylate cyclase (sGC) serves as a receptor for the signaling agent nitric oxide (NO). sGC synthesis of cGMP is regulated by NO, GTP, ATP, and allosteric activators such YC-1. The activity adenylate full-length catalytic domain constructs (alpha1(cat)beta1(cat)) are reported here. ATP mixed-type inhibitor production both alpha1(cat)beta1(cat), indicating that C-terminus contains an nucleotide binding site. YC-1 did not activate alpha1(cat)beta1(cat) or compete with inhibition...
Small numbers of hematopoietic stem cells (HSCs) generate large mature effector through the successive amplification transiently proliferating progenitor cells. HSCs and their downstream progenitors have been extensively characterized based on cell-surface phenotype functional activities during transplantation assays. These dynamically lose acquire specific sets surface markers differentiation, leading to identification that allow for more refined separation from early progenitors. Here, we...