A5003561532- Cardiac Valve Diseases and Treatments
- Cardiac, Anesthesia and Surgical Outcomes
- Tissue Engineering and Regenerative Medicine
- Pluripotent Stem Cells Research
- Anesthesia and Sedative Agents
- Anesthesia and Neurotoxicity Research
- Anesthesia and Pain Management
- Mesenchymal stem cell research
- Congenital Heart Disease Studies
- Respiratory Support and Mechanisms
- Cardiac Structural Anomalies and Repair
- Hedgehog Signaling Pathway Studies
- Cellular Mechanics and Interactions
- Cardiac tumors and thrombi
- Reproductive Biology and Fertility
- Developmental Biology and Gene Regulation
- Airway Management and Intubation Techniques
- Mechanical Circulatory Support Devices
- Pulmonary Hypertension Research and Treatments
- Assisted Reproductive Technology and Twin Pregnancy
- 3D Printing in Biomedical Research
- CRISPR and Genetic Engineering
- Tracheal and airway disorders
- Cardiomyopathy and Myosin Studies
- Adrenal Hormones and Disorders
Medical College of Wisconsin
2020-2025
Imamura Hospital
2024-2025
University of Michigan–Ann Arbor
2015-2021
University of Virginia
2009-2016
Ann Arbor Center for Independent Living
2016
Aso Iizuka Hospital
2003-2013
Kyushu University
2008-2012
University of Minnesota
2005-2009
Twin Cities Orthopedics
2008
Gunma Prefectural Cardiovascular Center
2001
Development of the asymmetric amniotic sac-with embryonic disc and ectoderm occupying opposite poles-is a vital milestone during human embryo implantation. Although essential to embryogenesis pregnancy, sac development in humans remains poorly understood. Here, we report pluripotent stem cell (hPSC)-based model, termed post-implantation embryoid (PASE), that recapitulates multiple embryogenic events centered around development. Without maternal or extraembryonic tissues, PASE self-organizes...
Melanopsin (Opn4) is a photopigment found in subset of retinal ganglion cells (RGCs) that project to various brain areas. These neurons are intrinsically photosensitive (ipRGCs) and implicated nonimage-forming responses environmental light such as the pupillary reflex circadian entrainment. Recent evidence indicates ipRGCs respond at birth, but questions remain whether when they undergo significant functional changes. We used bacterial artificial chromosome transgenesis engineer mouse line...
We demonstrate that dissociated human pluripotent stem cells (PSCs) are intrinsically programmed to form lumens. PSCs two-cell cysts with a shared apical domain within 20 hr of plating; these collapse monolayers after 5 days. Expression pluripotency markers is maintained throughout this time. In cysts, an domain, marked by EZRIN and atypical PKCζ, surrounded apically targeted organelles (early endosomes Golgi). Molecularly, actin polymerization, regulated ARP2/3 mammalian diaphanous-related...
Actin filament assembly in nonmuscle cells is regulated by the actin polymerization machinery, including Arp2/3 complex and formins. However, little known about regulation of muscle cells, where straight filaments are organized into contractile unit sarcomere. Here, we show that Fhod3, a myocardial formin localizes to thin striated pattern, regulates sarcomere organization cardiomyocytes. RNA interference-mediated depletion Fhod3 results marked reduction filamentous disruption sarcomeric...
Holoprosencephaly (HPE) is a severe human genetic disease affecting craniofacial development, with an incidence of up to 1/250 conceptions and 1.3 per 10,000 live births. Mutations in the Sonic Hedgehog (SHH) gene result HPE humans mice, Shh pathway targeted by other mutations that cause HPE. However, at least 12 loci are associated humans, suggesting defects pathways contribute this disease. Although TGIF1 (TG-interacting factor) maps HPE4 locus, heterozygous loss function HPE, mouse models...
Abstract The weakly inwardly rectifying K + channel Kir4.1 is found in many glial cells including astrocytes. However, questions remain regarding the relative contribution of to resting conductance mature astrocytes situ. We employed a bacterial artificial chromosome transgenic approach mice visualize expression vivo. These (Kir4.1‐EGFP) express enhanced green fluorescent protein (EGFP) under transcriptional control promoter. brains adult Kir4.1‐EGFP showed co‐expression EGFP and In...
Renovascular hypertension (RVHT) is most commonly caused by renal artery stenosis (RAS) secondary to arteriosclerosis. Other causes of RVHT include fibromuscular dysplasia (FMD) and other rare causes, such as Takayasu arteritis (TA). A male patient in his early 20s presented with hypertension. Laboratory findings were positive for hypokalemia well elevations plasma renin activity aldosterone concentration. Plain computed tomography revealed atrophy the right kidney, magnetic resonance...
Tgif1 and Tgif2 are transcriptional co-repressors that limit the response to TGFbeta signaling play a role in regulating retinoic-acid-mediated gene expression. Mutations human TGIF1 associated with holoprosencephaly, but it is unclear whether this result of deregulation TGFbeta/Nodal signaling, or effects on other pathways. Surprisingly, mutation mice results only relatively mild developmental phenotypes most strain backgrounds. Here, we show loss-of-function mutations both failure...
Human pluripotent stem cells (hPSCs) self-organize into apicobasally polarized cysts, reminiscent of the lumenal epiblast stage, providing a model to explore key morphogenic processes in early human embryos. Here, we show that apical polarization begins on interior single hPSCs through dynamic formation highly organized perinuclear apicosome structure. The membrane surrounding is enriched markers and displays microvilli primary cilium; its space rich Ca2+. Time-lapse imaging isolated reveals...
Murine intestinal villi are rapidly demarcated by patterned intraepithelial forces that induced mesenchymal cell clusters and accelerated division.
The transcriptional activity of LIM-homeodomain (LIM-HD) proteins is regulated by their interactions with various factors that bind to the LIM domain. We show reduced expression single-stranded DNA-binding protein 1 (Ssdp1), which encodes a co-factor domain interacting (Ldb1), in mouse mutant headshrinker (hsk) disrupts anterior head development partially mimicking Lim1 mutants. Although visceral endoderm and definitive endoderm, together comprise organizer, were able form normally...
The formin family proteins play pivotal roles in actin filament assembly via the FH2 domain. mammalian Fhod3 is highly expressed heart, and its mRNA adult heart contains exons 11, 12, 25, which are absent from non-muscle isoforms. In cultured neonatal cardiomyocytes, localizes to middle of sarcomere appears function organization, although it suggested that differently heart. Here we show, using immunohistochemical analysis with three different antibodies, each recognizing distinct regions...
Neural rosettes (NPC rosettes) are radially arranged groups of cells surrounding a central lumen that arise stochastically in monolayer cultures human pluripotent stem cell (hPSC)-derived neural progenitor (NPC). Since NPC rosette formation is thought to mimic behavior the early tube, these represent important vitro models for study tube morphogenesis. However, using current protocols, not synchronized and results inconsistent among different hPSC lines, hindering quantitative mechanistic...
Critical early steps in human embryonic development include polarization of the inner cell mass, followed by formation an expanded lumen that will become epiblast cavity. Recently described three-dimensional (3D) pluripotent stem cell-derived cyst (hPSC-cyst) structures can replicate these processes. To gain mechanistic insights into poorly understood machinery involved cavity formation, we interrogated proteomes apical and basolateral membrane territories 3D hPSC-cysts. APEX2-based...
Mouse embryos conditionally lacking Tgif1 and Tgif2 have holoprosencephaly defects in left-right asymmetry. To identify pathways affected by loss of Tgif function during embryogenesis, we performed transcriptome profiling on whole mouse embryos. Among the genes with altered expression Tgifs were a number links to cilium function. One these, Evi5l, encodes RabGAP that is known block formation cilia when overexpressed. Evi5l increased Tgif1; Tgif2-null double-null embryo fibroblasts (MEFs)....