A5103146970- Circadian rhythm and melatonin
- Retinal Development and Disorders
- Photoreceptor and optogenetics research
- Retinopathy of Prematurity Studies
- Wnt/β-catenin signaling in development and cancer
- Cancer-related gene regulation
- Neonatal Respiratory Health Research
- Retinal Diseases and Treatments
- Epigenetics and DNA Methylation
- Lysosomal Storage Disorders Research
- Angiogenesis and VEGF in Cancer
- Retinal Imaging and Analysis
- Hepatocellular Carcinoma Treatment and Prognosis
- Cancer Genomics and Diagnostics
- Adipose Tissue and Metabolism
- Lymphatic System and Diseases
- Pancreatic and Hepatic Oncology Research
- Biomedical Research and Pathophysiology
- Cancer Mechanisms and Therapy
- Colorectal and Anal Carcinomas
- Light effects on plants
- Sympathectomy and Hyperhidrosis Treatments
- Kruppel-like factors research
- Axon Guidance and Neuronal Signaling
- Retinal and Optic Conditions
Case Western Reserve University
2015-2024
Cleveland Clinic Lerner College of Medicine
2015-2024
Cleveland Eye Clinic
2014-2024
Cleveland Clinic
2015-2024
Eli Lilly (United States)
2020-2022
Cincinnati Children's Hospital Medical Center
2007-2018
University of Cincinnati
2005-2013
University of Washington
2013
Fred Hutch Cancer Center
2005
Macrophages are required for tissue homeostasis through their role in regulation of the immune response and resolution injury. Here we show, using kidney as a model, that Wnt pathway ligand Wnt7b is produced by macrophages to stimulate repair regeneration. When inducibly ablated from injured kidney, canonical epithelial cells reduced. Furthermore, when somatically deleted macrophages, injury greatly diminished. Finally, injection regulator Dkk2 enhances process suggests therapeutic option....
Recent genome-wide association studies of individuals Asian and European descent have found that SNPs located within the genomic region (1p31.3) encoding Wntless (Wls)/Gpr177 protein are associated significantly with reduced bone mineral density. Wls / Gpr177 is a newly identified chaperone specifically escorts Wnt ligands for secretion. Given strong functional between signaling pathways development homeostasis, we generated osteoblast-specific Wls-deficient ( Ocn-Cre;Wls-flox ) mice....
Abstract The Wnt‐signaling pathway is necessary in a variety of developmental processes and has been implicated numerous pathologies. Wntless (Wls) binds to Wnt proteins facilitates sorting secretion. Conventional deletion Wls results early fetal lethality due defects body axis establishment. To gain insight into the function later stages development, we have generated conditional null allele. Homozygous germline confirmed prenatal failure embryonic formation. Deletion using Wnt1‐cre...
Macrophages have been suggested to stimulate neo-lymphangiogenesis in settings of inflammation via two potential mechanisms: (1) acting as a source lymphatic endothelial progenitor cells the ability transdifferentiate into and be incorporated growing vessels; (2) providing crucial pro-lymphangiogenic growth factors proteases. We set out establish whether myeloid lineage are important for development vasculature through either these mechanisms. Here, we provide tracing evidence demonstrate...
PURPOSE SEQUOIA compared efficacy and safety of adding pegilodecakin (PEG), a pegylated recombinant human interleukin (IL)-10, with folinic acid, fluorouracil, oxaliplatin (FOLFOX) in patients following progression on first-line gemcitabine-containing therapy metastatic pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS SEQUOIA, randomized, global phase III study, FOLFOX PEG + as second line gemcitabine-refractory PDAC. Patients were randomly assigned 1:1 (PEG FOLFOX:FOLFOX)...
Almost all life forms can detect and decode light information for adaptive advantage. Examples include the visual system, in which photoreceptor signals are processed into virtual images, circadian entrains a physiological clock. Here we describe response pathway mice that employs encephalopsin (OPN3, 480 nm, blue-light-responsive opsin) to regulate function of adipocytes. Germline null adipocyte-specific conditional show light- Opn3-dependent deficit thermogenesis become hypothermic upon...
Macrophages have a critical function in the recognition and engulfment of dead cells. In some settings, macrophages also actively signal programmed cell death. Here we show that during developmentally scheduled vascular regression, resident are an obligatory participant signaling switch favors death over survival. This occurs when ligand angiopoietin 2 has dual effect suppressing survival endothelial cells (VECs) stimulating Wnt production by macrophages. response to ligand, VECs enter cycle...
Circadian clocks regulate various aspects of photoreceptor physiology, but their contribution to development and function is unclear. Cone photoreceptors are critical for color vision. Here, we define the molecular circadian activity within cone reveal a role clock genes Bmal1 Per2 in regulating spectral identity. ChIP analysis revealed that BMAL1 binds promoter region thyroid hormone (TH)-activating enzyme type 2 iodothyronine deiodinase (Dio2) thus regulates expression Dio2. TH treatment...
The Wnt/β-catenin response pathway is central to many developmental processes. Here, we assessed the role of Wnt signaling in early eye development using mouse as a model system. We showed that surface ectoderm region includes lens placode expressed 12 out 19 possible ligands. When these activities were suppressed by conditional deletion wntless (Le-cre; Wlsfl/fl) there dramatic consequences included saucer-shaped optic cup, ventral coloboma, and deficiency periocular mesenchyme. This...
Particulate matter ≤2.5μm (PM2.5) air pollution is a leading environmental risk factor contributing disproportionately to the global burden of non-communicable disease. We compared impact chronic exposure PM2.5 alone, or with light at night (LL) on metabolism. induced peripheral insulin resistance, circadian rhythm (CR) dysfunction, and metabolic brown adipose tissue (BAT) akin LL (with no additive interaction between LL). Transcriptomic analysis liver BAT revealed widespread but unique...
Normal development requires tight regulation of cell proliferation and death. Here, we have investigated these control mechanisms in the hyaloid vessels, a temporary vascular network mammalian eye that Wnt/β-catenin response for scheduled regression. We whether Wnt was linked to oncogene Myc, cyclin-dependent kinase inhibitor CDKN1A (P21), both established regulators cycle progression Our analysis showed pathway co-receptors LRP5 LRP6 overlapping activities mediate signaling endothelial...
A single pool of multipotent retinal progenitor cells give rise to the diverse cell types within mammalian retina. Such cellular diversity is due precise control various processes like specification, proliferation, differentiation, and maturation. Circadian clock genes can expression key regulators cycle progression therefore synchronize state a heterogeneous population cells. Here we show that protein encoded by circadian gene brain muscle arnt-like protein-1 (
Ramucirumab is indicated for patients with advanced hepatocellular carcinoma (HCC) and α-fetoprotein (AFP) ≥400 ng/mL following sorafenib. Here, we prospectively studied ramucirumab non-sorafenib systemic therapies.This open-label, non-comparative cohort of REACH-2 enrolled HCC, Child-Pugh class-A liver disease, AFP who had received 1-2 lines therapy, excluding sorafenib or chemotherapy. was administered 8 mg/kg intravenously Q2W. The primary endpoint safety. Secondary endpoints were overall...
Abstract The Hippo-YAP/TAZ-TEAD signaling pathway plays critical roles in tumorigenesis and tumor progression. Genetic alterations of Hippo regulators, such as NF2 or LATS1/2, have been shown to induce YAP/TAZ-TEAD transcriptional activity, promoting initiation progression many solid tumors. In addition, studies that activation mediates resistance multiple targeted therapies, particularly EGFR-KRas-MAPK inhibitors. TEAD family transcription factors (TEAD1/2/3/4) share structural similarity...
To date, there are no effective antiviral medications for COVID-19. Drug repurposing, a strategy that uses existing drugs, offers potential prevention and treatment options We discuss one combines anti-inflammatory (melatonin) (toremifene) agents patients infected with SARS-CoV-2 from network medicine-based findings. also describe the pathobiology immunologic characteristics of COVID-19 highlight rationale combination drug to rescue pulmonary cardiovascular conditions resulting A preliminary...
637 Background: Effective therapies are limited for advanced metastatic pancreatic ductal adenocarcinoma (PDAC) patients (pts) who have progressed after 1 st line gemcitabine-based chemotherapy (Gem). FOLFOX has clinical benefit in Gem-refractory PDAC pts. A phase trial demonstrated promising activity with pegilodecakin (PEG; pegylated IL-10) and pts, providing rationale the 3 (SEQUOIA; NCT02923921). Methods: SEQUOIA is a randomized study of alone or PEG Pts were 1:1, excluding pts prior...