A5012601024- TGF-β signaling in diseases
- Angiogenesis and VEGF in Cancer
- Kruppel-like factors research
- Cell Adhesion Molecules Research
- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Cancer, Hypoxia, and Metabolism
- Ovarian cancer diagnosis and treatment
- Cancer Cells and Metastasis
- Metabolism, Diabetes, and Cancer
- Connective Tissue Growth Factor Research
- Caveolin-1 and cellular processes
- Pancreatic and Hepatic Oncology Research
- Hippo pathway signaling and YAP/TAZ
- Congenital heart defects research
- Biomarkers in Disease Mechanisms
- Epigenetics and DNA Methylation
- Protein Kinase Regulation and GTPase Signaling
- Genomics, phytochemicals, and oxidative stress
- Proteoglycans and glycosaminoglycans research
- RNA modifications and cancer
- Monoclonal and Polyclonal Antibodies Research
- Histone Deacetylase Inhibitors Research
- Peptidase Inhibition and Analysis
- Signaling Pathways in Disease
University of Arizona
2018-2025
University of Arizona Cancer Center
2019-2020
The Ohio State University
2014-2018
Lung Institute
2012-2016
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
2015-2016
Duke University
2009-2012
Duke Medical Center
2007-2009
Duke University Hospital
2007-2009
Samsung Medical Center
2009
Sungkyunkwan University
2009
Transforming growth factor beta (TGF-beta) signals through two distinct pathways to regulate endothelial cell proliferation, migration, and angiogenesis, the ALK-1/Smad 1/5/8 ALK-5/Smad2/3 pathways. Endoglin is a co-receptor predominantly expressed in cells that participates TGFbeta-mediated signaling with ALK-1 ALK-5 regulates critical aspects of cellular biological responses. The embryonic lethal phenotype knock-out mice because defects angiogenesis disease-causing mutations resulting...
Growth factors in tumor environments are regulators of cell survival and metastasis. Here, we reveal the dichotomy between TGF-β superfamily growth BMP TGF-β/activin their downstream SMAD effectors. Gene expression profiling uncovers SOX2 as a key contextual signaling node regulated an opposing manner by BMP2, -4, -9 activin A to impact anchorage-independent survival. We find that is repressed BMPs, leading reduction intraperitoneal burden improved tumor-bearing mice. Repression driven...
In endothelial cells, transforming growth factor β (TGF-β) signals through two distinct pathways to regulate cell proliferation and migration, the ALK-1/Smads 1/5/8 pathway ALK-5/Smads 2/3 pathway. TGF-β signaling these is further regulated in cells by specific superfamily co-receptor, endoglin. The importance of endoglin, ALK-1, ALK-5 biology underscored embryonic lethal phenotypes knock-outs mice due defects angiogenesis, presence disease-causing mutations genes human vascular diseases....
Endoglin, an endothelial cell-specific transforming growth factor-β (TGF-β) superfamily coreceptor, has essential role in angiogenesis. Endoglin-null mice have embryonic lethal phenotype due to defects angiogenesis and mutations endoglin result the vascular disease hereditary hemorrhagic telangiectasia type I. Increased expression proliferating endothelium of tumors been correlated with metastasis, tumor grade decreased survival. Although is thought regulate TGF-β signaling cells through...
Ovarian cancer remains the most lethal gynecologic malignancy, and is primarily diagnosed at late stage when considerable metastasis has occurred in peritoneal cavity. At abdominal cavity ascites accumulation provides a tumor-supporting medium which cells gain access to growth factors cytokines that promote survival metastasis. However, little known about redox status of ascites, or whether antioxidant enzymes are required support ovarian during transcoelomic this medium. Gene expression...
Acetylation of microtubules (MT) confers mechanical stability necessary for numerous functions including cell cycle and intracellular transport. Although αTAT1 is a major MT acetyltransferase, how this enzyme regulated remains much less clear. Here we report TGF-β-activated kinase 1 (TAK1) as key activator αTAT1. TAK1 directly interacts with phosphorylates at Ser237 to critically enhance its catalytic activity, mutating site alanine abrogates, whereas phosphomimetic induces hyperacetylation...
Insulin-stimulated glucose uptake is known to involve microtubules, although the function of microtubules and microtubule-regulating proteins involved in insulin action are poorly understood. CLASP2, a plus-end tracking microtubule-associated protein (+TIP) that controls microtubule dynamics, was recently implicated as first +TIP associated with insulin-regulated uptake. Here, using protein-specific targeted quantitative phosphoproteomics within 3T3-L1 adipocytes, we discovered regulates...
Transforming growth factor-beta (TGF-beta) signals through three highly conserved cell surface receptors, the type III TGF-beta receptor (T beta RIII), II RII), and I RI) to regulate diverse cellular processes including proliferation, differentiation, migration, apoptosis. Although T RI RII undergo ligand-independent endocytosis by both clathrin-mediated endocytosis, resulting in enhanced signaling, clathrin-independent degradation, mechanism function of RIII is poorly understood. a heparan...
Loss of expression the type III transforming growth factor-β receptor (TβRIII or betaglycan), a (TGF-β) superfamily co-receptor, is common in human breast cancers. TβRIII suppresses cancer progression vivo by reducing cell migration and invasion largely unknown mechanisms. Here, we demonstrate that cytoplasmic domain essential for TβRIII-mediated downregulation vitro inhibition . Functionally, required to attenuate TGF-β signaling, whereas attenuation signaling invasion. Mechanistically,...
The importance of macrophages in kidney diseases has been well established; however, the mechanisms underlying infiltration into injured kidneys are not understood. RGMb is a member repulsive guidance molecule (RGM) family. can be expressed on cell surface but large portion localized intracellularly. Among various immune types, express highest levels RGMb, biological functions remain largely unknown. We find that promoted macrophage migration vitro and vivo, enhanced aggravated inflammation...
Endoglin (CD105) is an endothelial-specific transforming growth factor β (TGF-β) coreceptor essential for angiogenesis and vascular homeostasis. Although endoglin dysfunction contributes to numerous conditions, the mechanism of action remains poorly understood. Here we report a novel in which Gα-interacting protein C-terminus-interacting (GIPC)-mediated trafficking phosphatidylinositol 3-kinase (PI3K) regulates endothelial signaling function. We demonstrate that interacts with PI3K subunits...
Abstract Inhibin is a heterodimeric TGFβ family ligand that expressed in many cancers and selective biomarker for ovarian cancers; however, its tumor-specific functions remain unknown. Here, we demonstrate the α subunit of inhibin (INHA), which critical functionality dimeric A/B, correlates with microvessel density human tissues predictive poor clinical outcomes multiple cancers. We inhibin-regulated angiogenesis necessary metastasis. Although had no direct impact on tumor cell signaling,...
Abstract Defective angiogenesis underlies over 50 malignant, ischemic and inflammatory disorders yet long-term therapeutic applications inevitably fail, thus highlighting the need for greater understanding of vast crosstalk compensatory mechanisms. Based on proteomic profiling angiogenic endothelial components, here we report β IV -spectrin, a non-erythrocytic cytoskeletal protein, as critical regulator sprouting angiogenesis. Early loss endothelial-specific -spectrin promotes embryonic...
Abstract In pathologies including cancer, aberrant Transforming Growth Factor-β (TGF-β) signaling exerts profound tumor intrinsic and extrinsic consequences. Intense clinical endeavors are underway to target this pathway. Central the success of these interventions is pinpointing factors that decisively modulate TGF-β responses. Betaglycan/type III receptor (TβRIII), an established co-receptor for superfamily known bind directly TGF-βs 1–3 inhibin A/B. Betaglycan can be membrane-bound also...
Dynamic changes in the endoplasmic reticulum (ER) morphology are central to maintaining cellular homeostasis. Microtubules (MT) facilitate continuous remodeling of ER network into sheets and tubules by coordinating with many ER-shaping protein complexes, although how this process is controlled extracellular signals remains unknown. Here we report that TAK1, a kinase responsive various growth factors cytokines including TGF-β TNF-α, triggers tubulation activating αTAT1, an MT-acetylating...
Autophagy is the targeted degradation of proteins and organelles critical for homeostasis cell survival. Transforming growth factor β (TGF-β) differentially regulates autophagy in a context-specific manner, although precise intracellular mechanisms remain less clear. Importantly, how TGF-β controls autophagic responses endothelial cells (EC) during angiogenesis unknown. Here we identified endoglin, an EC-specific co-receptor essential angiogenesis, as key determinant autophagy. Among two...
Abstract Hypoxia, a driver of tumor growth and metastasis, regulates angiogenic pathways that are targets for vessel normalization ovarian cancer management. However, toxicities resistance to anti-angiogenics can limit their use making identification new vital. Inhibin, heteromeric TGFβ ligand, is contextual regulator progression acting as an early suppressor, yet also established biomarker cancers. Here, we find hypoxia increases inhibin levels in cell lines, xenograft tumors, patients....
Abstract The C‐terminal phosphorylation domain of the epidermal growth factor receptor is believed to regulate protein kinase activity as well mediate assembly signal transduction complexes. structure and dynamics this proposed autoregulatory were examined by labeling extreme C terminus EGFR intracellular (ICD) with an extrinsic fluorophore. Fluorescence anisotropy decay analysis nonphosphorylated EGFR‐ICD yielded two rotational correlation times: a longer time, consistent global motion 60‐...