- Optical Coherence Tomography Applications
- Immunotherapy and Immune Responses
- Advanced Fluorescence Microscopy Techniques
- Photoacoustic and Ultrasonic Imaging
- Neonatal Respiratory Health Research
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- IL-33, ST2, and ILC Pathways
- Glaucoma and retinal disorders
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Cancer-related gene regulation
- Cancer Immunotherapy and Biomarkers
- Asthma and respiratory diseases
- Immune cells in cancer
- Lymphatic System and Diseases
- Sepsis Diagnosis and Treatment
- Extracellular vesicles in disease
- Retinal and Optic Conditions
- Dermatology and Skin Diseases
- Thermal Regulation in Medicine
- Cancer and Skin Lesions
- Ear and Head Tumors
- Angiogenesis and VEGF in Cancer
- Chemokine receptors and signaling
23andMe (United States)
2025
Teva Pharmaceuticals (United States)
2024
Stanford University
2016-2018
University of California, San Francisco
2010-2018
Pfizer (United States)
2018
Stanford Medicine
2017
Institute of Post Graduate Medical Education and Research
2016
Howard Hughes Medical Institute
2012
University of California, Irvine
2008-2010
Institute of Molecular Biology and Biophysics
2008
For efficient development of an immune response, T lymphocytes require long-lasting calcium influx through release-activated (CRAC) channels and the formation a stable immunological synapse (IS) with antigen-presenting cell (APC). Recent RNAi screens have identified Stim Orai in Drosophila cells, their corresponding mammalian homologs STIM1 Orai1 as essential for CRAC channel activation. Here, we show that are recruited to between primary human cells autologous dendritic cells. Both...
Asthma pathogenesis is focused around conducting airways. The reasons for this focus have been unclear because it has not possible to track the sites and timing of antigen uptake or subsequent presentation effector T cells. In study, we use two-photon microscopy lung parenchyma note accumulation CD11b+ dendritic cells (DCs) airway after allergen challenge but very limited access these airway-adjacent DCs contents airspace. contrast, observed prevalent transepithelial particulate antigens by...
Optical coherence tomography (OCT) is a powerful biomedical imaging technology that relies on the coherent detection of backscattered light to image tissue morphology in vivo. As consequence, OCT susceptible noise (speckle noise), which imposes significant limitations its diagnostic capabilities. Here we show method based purely manipulation able entirely remove speckle originating from turbid samples without any compromise resolution. We refer this as Speckle-Free (SFOCT). Using SFOCT,...
4-1BB (CD137, TNFRSF9) is an inducible costimulatory receptor expressed on activated T cells. Clinical trials of two agonist antibodies, utomilumab (PF-05082566) and urelumab (BMS-663513), are ongoing in multiple cancer indications, both antibodies demonstrate distinct activities the clinic. To understand these differences, we solved structures human 4-1BB/4-1BBL complex, 4-1BBL trimer alone, bound to or urelumab. The complex displays a unique interaction between ligand when compared with...
Abstract Optical Coherence Tomography (OCT) enables real-time imaging of living tissues at cell-scale resolution over millimeters in three dimensions. Despite these advantages, functional biological studies with OCT have been limited by a lack exogenous contrast agents that can be distinguished from tissue. Here we report an approach to implements custom algorithms spectrally identify unique agents: large gold nanorods (LGNRs). LGNRs exhibit 110-fold greater spectral signal per particle than...
Telomerase activity in leukemic blasts frequently is increased among patients with high-risk acute myeloid leukemia (AML). In the current study, authors evaluated feasibility, safety, immunogenicity, and therapeutic potential of human telomerase reverse transcriptase (hTERT)-expressing autologous dendritic cells (hTERT-DCs) adult AML.hTERT-DCs were produced from patient-specific leukapheresis, electroporated an mRNA-encoding hTERT a lysosomal-targeting sequence, cryopreserved. A total 22...
Coordinated efforts between macrophages and epithelia are considered essential for wound healing, but the macrophage-derived molecules responsible repair poorly defined. This work demonstrates that lung rely upon Trefoil factor 2 to promote epithelial proliferation following damage caused by sterile wounding, Nippostrongylus brasiliensis or Bleomycin sulfate. Unexpectedly, presence of T, B, ILC populations was not macrophage-driven repair. Instead, conditional deletion TFF2 in...
Dendritic cells (DCs) initiate and polarize adaptive immune responses toward varying functional outcomes. By means of intravital two-photon microscopy, we report that dermal dendritic (DDCs) Langerhans (LCs) are differentially mobilized during contact sensitization by adjuvants such as unmethylated CpG oligonucleotide (CpG) LPS induce T helper type 1 (Th1) responses, or papain induces 2 (Th2) responses. In ear pinna, sensitization, CpG, LPS, all DDCs in three distinct phases: increased...
<p>Supplementary Figure S5</p>
<p>Supplementary Figure S4</p>
<p>Supplementary Figure S8</p>
<p>Supplementary Figure S9</p>
<p>Supplementary Figure S6</p>
<p>Characterization of the binding and blocking activity 23ME-01473</p>
<p>Supplementary Figure S7</p>
Abstract The landscape of cancer treatment has been transformed by immune checkpoint inhibitors; however, the failure to benefit a large number patients with underlined need identify promising targets for more effective interventions. In this study, we leverage 23andMe, Inc.’s large-scale human germline genetic and health database uncover previously unknown role UL16-binding protein 6 (ULBP6), high-affinity NK group 2D (NKG2D) ligand, in its promise as an immuno-oncology therapeutic target....
<p>List of collaborators from 23andMe Research Team</p>
<p>23ME-01473 significantly inhibits the growth of a NSCLC patient-derived xenograft cancer model <i>in vivo.</i><b>A,</b> Cell surface expression ULBP6/2/5 on EpCAM<sup>+</sup> tumor cells from CTG-3470 PDX cell line implanted and grown in NOG mice as measured by flow cytometry. Data three biological replicates are shown. <b>B,</b> Representative IHC images or MICA/B (top) corresponding isotype controls (bottom) resected tumors....
<p>Supplementary Figure S3</p>
<p>Dual FcγRIIIa and NKG2D activation by 23ME-01473, an Fc effector–enhanced anti-ULBP6/2/5 antibody, induces augmented antitumor immunity. <b>A,</b> IFNγ concentration of the supernatants IL-2/IL-15–primed PBMCs cultured with plate-bound antibodies that activate (Fc-WT-anti-lysozyme antibody; X-lys-E+), (Fc-Att-anti-lysozyme antibody fused to ULBP6-02; ULBP6-lys-E−), both receptors ULBP6-lys-E+), or neither receptor X-lys-E−) for 24 hours. Data represent mean ± SD three...
<p>Supplementary Figure S1</p>
<p>mRNA and protein expression of NKG2D ligands in human cancers. <b>A,</b> Heatmap the median mRNA NKG2DLs per cancer type The Cancer Genome Atlas. types are sorted by <i>RAET1L</i> (ULBP6). <b>B,</b> <i>ULBP2</i>, <i>RAET1G</i>, (ULBP5) stromal, immune, malignant cells (<i>N</i> = 5,902) from 18 treatment-naive patients with HNSC. <b>C,</b> Representative IHC images ULBP6/2/5 HNSC LUSC tumors (top)...
<div>Abstract<p>The landscape of cancer treatment has been transformed by immune checkpoint inhibitors; however, the failure to benefit a large number patients with underlined need identify promising targets for more effective interventions. In this study, we leverage 23andMe, Inc.’s large-scale human germline genetic and health database uncover previously unknown role UL16-binding protein 6 (ULBP6), high-affinity NK group 2D (NKG2D) ligand, in its promise as an immuno-oncology...
<p><i>RAET1L</i> (ULBP6) germline genetics. Regional GWAS plots of the three <i>RAET1L</i> variants: rs1543547, rs1555696, and rs61730071, identified in credible set that are significantly associated with (<b>A</b>) alopecia areata (<b>B</b>) basal cell carcinoma. The fourth variant, rs912565, is not either phenotype. <b>C,</b> variants, but showed significant (<i>P</i> < 5 × 10<sup>−8</sup>)...