A5075772920- Genetic and Kidney Cyst Diseases
- Hedgehog Signaling Pathway Studies
- Renal and related cancers
- Epigenetics and DNA Methylation
- Wnt/β-catenin signaling in development and cancer
- Protist diversity and phylogeny
- Digestive system and related health
- Cancer Cells and Metastasis
- PI3K/AKT/mTOR signaling in cancer
- Radiopharmaceutical Chemistry and Applications
- Medical Imaging Techniques and Applications
- Connective tissue disorders research
- Genetic factors in colorectal cancer
- Renal cell carcinoma treatment
- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- Fibroblast Growth Factor Research
- Multiple and Secondary Primary Cancers
- Protein Degradation and Inhibitors
- Amoebic Infections and Treatments
- Heat shock proteins research
- Advanced Electron Microscopy Techniques and Applications
- FOXO transcription factor regulation
- Cancer Mechanisms and Therapy
- Nutrition and Health in Aging
University of Virginia
2014-2024
Hangzhou City University
2024
University of South China
2022
Shanghai Xuhui Central Hospital
2022
University of Virginia Cancer Center
2021
Nanjing University
2021
Tianjin Medical University
2020
Shandong Tumor Hospital
2019
Shandong First Medical University
2019
Center for Global Health
2014-2016
Malnutrition and cryptosporidiosis form a vicious cycle lead to acute long-term growth impairment in children from developing countries. Insights into mechanisms underlying the will help design rational therapies mitigate this infection. We tested effect of short-term protein malnutrition on Cryptosporidium parvum infection murine model by examining stool shedding, tissue burden, histologic change explored mechanism interaction between through immunostaining immunoblotting. Protein increased...
MAK (male germ cell-associated protein kinase) and MRK/ICK (MAK-related kinase/intestinal cell are human homologs of Ime2p in Saccharomyces cerevisiae Mde3 Pit1 Schizosaccharomyces pombe similar to cyclin-dependent kinase 2 (CDK2) extracellular signal-regulated (ERK2). MRK require dual phosphorylation a TDY motif catalyzed by an unidentified threonine tyrosine autophosphorylation. Herein, we establish that CDK-related CCRK (cell cycle-related is activating T157 for MRK, whereas active...
Significance A properly functioning primary cilium is prerequisite for both normal development and aging of all ciliated organisms, including humans. In vertebrates, the signaling Hedgehog family morphogens depends entirely on cilium. Recently, we reported that fibroblast growth factors (FGF) interacts with Hedgehog, this a consequence FGF regulating length speed processes happen therein. report, provide molecular mechanism such interaction, identifying intestinal cell kinase as mediator...
Male germ cell-associated kinase (MAK) and intestinal cell (ICK) are nuclear Cdc2-related kinases with nearly identical N-terminal catalytic domains more divergent C-terminal noncatalytic domains. The domain is also related to mitogen-activated protein (MAPKs) contains a corresponding TDY motif. Nuclear localization of ICK requires subdomain XI interactions the conserved Arg-272, but not activity or, surprisingly, any domain. Further, required for its activation. activated by dual...
Intestinal cell kinase (ICK), originally cloned from the intestine and expressed in intestinal crypt epithelium, is a highly conserved serine/threonine protein that similar to mitogen-activated kinases (MAPKs) catalytic domain requires dual phosphorylation within MAPK-like TDY motif for full activation. Despite these similarities MAPKs, biological functions of ICK remain unknown. In this study, we report suppression expression cultured epithelial cells by short hairpin RNA (shRNA)...
Objective: To investigate the association between semaphorin 3A (SEMA 3A) and its receptor neuropilin 1 (NRP1) clinicopathologic characteristics of patients with tongue cancer.Study Design: Forty-three squamous cell carcinoma specimens were included.Immunohistochemical staining SEMA3A NRP1 was performed on 15 normal epithelium 43 tumour specimens.Immunoreactivity evaluated based intensity distribution score.Statistical analyses using Chi-squared Spearman tests Kaplan-Meier analysis.Results:...
Loss-of-function mutations in the human
Human endocrine-cerebro-osteodysplasia (ECO) syndrome, caused by the loss-of-function mutation R272Q in intestinal cell kinase (ICK) gene, is a neonatal-lethal developmental disorder. To elucidate molecular basis of ECO we constructed an Ick knock-in mouse model that recapitulates pathological phenotypes. Newborns bearing homozygous mutations die at birth due to respiratory distress. mutant lungs exhibit not only impaired branching morphogenesis associated with reduced mesenchymal...
Mutations in human CILK1 (ciliogenesis associated kinase 1) are linked to ciliopathies and epilepsy. Homozygous point nonsense mutations that extinguish activity impair primary cilia function, whereas outside the domain not well understood. Here, we produced a knock-in mouse equivalent A615T variant identified juvenile myoclonic epilepsy (JME). This residue is intrinsically disordered C-terminal region of separate from domain. Mouse embryo fibroblasts (MEFs) with either heterozygous or...
ICK/MRK (intestinal cell kinase/MAK-related kinase), MAK (male germ cell-associated and MOK (MAPK/MAK/MRK-overlapping kinase) are closely related serine/threonine protein kinases in the kinome. The biological functions regulatory mechanisms of ICK/MAK/MOK family still largely elusive. Despite significant similarities their catalytic domains, they diverge markedly sequence structural organization C-terminal non-catalytic raising question as to whether have distinct, overlapping, or redundant...
Nutritional deficiency and stress can severely impair intestinal architecture, integrity host immune defense, leading to increased susceptibility infection cancer. Although the intestine has an inherent capability adapt environmental stress, molecular mechanisms by which senses responds malnutrition are not completely understood. We hereby report that cell kinase (ICK), a highly conserved serine/threonine protein kinase, is novel component of adaptive signaling responses in murine small...
Kinesin family member 3A (KIF3A) is a molecular motor protein in the heterotrimeric kinesin-2 complex that drives anterograde intraflagellar transport. This process plays pivotal role both biogenesis and maintenance of primary cilium supports tissue development. Ciliogenesis associated kinase 1 (CILK1) phosphorylates human KIF3A at Thr672. CILK1 loss function causes ciliopathies manifest profound multiplex developmental defects, including hydrocephalus, polydactyly, shortened hypoplastic...
Ciliopathies are a group of human genetic disorders associated with mutations that give rise to the dysfunction primary cilia. Ciliogenesis-associated kinase 1 (CILK1), formerly known as intestinal cell (ICK), is conserved serine and threonine restricts (non-motile) cilia formation length. Mutations in CILK1 ciliopathies also linked juvenile myoclonic epilepsy (JME). However, effects JME-related on activity function unknown. Here, we report JME pathogenic N-terminal domain abolish activity,...
The primary cilium provides cell sensory and signaling functions. Cilia structure function are regulated by ciliogenesis-associated kinase 1 (CILK1). Ciliopathies caused CILK1 mutations show longer cilia abnormal Hedgehog signaling. Our study aimed to identify small molecular inhibitors of that would enable pharmacological modulation cilia. A previous screen a chemical library for interactions with protein kinases revealed Alvocidib has picomolar binding affinity CILK1. In this study, we...
The primary cilium, the cell’s sensory and signaling antenna, is a dynamic cellular organelle during cell cycle. It resorbed before cells enter mitosis reformed after exit mitosis, as such acts structural barrier to mitosis. Cancer that undergo rapid cycle replication have low ciliation rate. Therefore, promoting cilia formation elongation thereby reducing their rates of retraction hold key blocking entry into slowing down cancer replication. To perform comprehensive efficient literature...
The primary cilium functions as a cellular sensory organelle and signaling antenna that detects transduces extracellular signals. Mutations in the human gene CILK1 (ciliogenesis associated kinase 1) cause abnormal cilia elongation faulty Hedgehog signaling, with developmental disorders epilepsy. is protein requires dual phosphorylation of its TDY motif for activation extended C-terminal intrinsically disordered region (IDR) mediates targeting to basal body substrate recognition. Proteomics...
Abstract Mutations in human CILK1 (ciliogenesis associated kinase 1) are linked to ciliopathies and epilepsy. Homozygous point nonsense mutations that extinguish activity impair primary cilia function, whereas outside the domain not well understood. Here, we produced a knock-in mouse equivalent of A615T variant identified juvenile myoclonic epilepsy (JME). This residue is C-terminal region separate from domain. Mouse embryo fibroblasts (MEF) with either heterozygous or homozygous A612T...