المؤلفون: Wichaidit, Chonlarat.

الوصف: Thesis (Ph.D.)--University of Wisconsin--Madison, 2006.
Includes bibliographical references (p. 141-151). Also available on the Internet.

الإتاحة: http://www.library.wisc.edu/databases/connect/dissertations.htmlTest

المؤلفون: Taylor, Clinton A., Cormier, Kevin W., Keenan, Shannon E., Earnest, Svetlana, Stippec, Steve, Wichaidit, Chonlarat, Juang, Yu-Chi, Wang, Junmei, Shvartsman, Stanislav Y., Goldsmith, Elizabeth J., Cobb, Melanie H.

المصدر: Proceedings of the National Academy of Sciences of the United States of America, 2019 Jul . 116(31), 15514-15523.

الوصول الحر: https://www.jstor.org/stable/26848148Test

المؤلفون: Liu, Zhenan, Yoon, Joonho, Wichaidit, Chonlarat, Jaykumar, Ankita B., Dbouk, Hashem A., Embry, Addie E., Liu, Liping, Henderson, Joel M., Chang, Audrey N., Cobb, Melanie H., Miller, Richard Tyler

المساهمون: University of Texas Southwestern Medical Center

المصدر: Frontiers in Cell and Developmental Biology ; volume 8 ; ISSN 2296-634X

مصطلحات موضوعية: Cell Biology, Developmental Biology

الوصف: Cytoskeletal structure and its regulation are essential for maintenance of the differentiated state of specific types of cells and their adaptation to physiologic and pathophysiologic conditions. Renal glomerular capillaries, composed of podocytes, endothelial cells, and the glomerular basement membrane, have distinct structural and biophysical properties and are the site of injury in many glomerular diseases. Calcineurin inhibitors, immunosuppressant drugs used for organ transplantation and auto-immune diseases, can protect podocytes and glomerular capillaries from injury by preserving podocyte cytoskeletal structure. These drugs cause complications including hypertension and hyperkalemia which are mediated by WNK (With No Lysine) kinases as well as vasculopathy with glomerulopathy. WNK kinases and their target kinases oxidative stress-responsive kinase 1 (OSR1) and SPS1-related proline/alanine-rich kinase (SPAK) have fundamental roles in angiogenesis and are activated by calcineurin inhibitors, but the actions of these agents on kidney vasculature, and glomerular capillaries are not fully understood. We investigated WNK1 expression in cultured podocytes and isolated mouse glomerular capillaries to determine if WNK1 contributes to calcineurin inhibitor-induced preservation of podocyte and glomerular structure. WNK1 and OSR1/SPAK are expressed in podocytes, and in a pattern similar to podocyte synaptopodin in glomerular capillaries. Calcineurin inhibitors increased active OSR1/SPAK in glomerular capillaries, the Young’s modulus (E) of glomeruli, and the F/G actin ratio, effects all blocked by WNK inhibition. In glomeruli, WNK inhibition caused reduced and irregular synaptopodin-staining, abnormal capillary and foot process structures, and increased deformability. In cultured podocytes, FK506 activated OSR1/SPAK, increased lamellipodia, accelerated cell migration, and promoted traction force. These actions of FK506 were reduced by depletion of WNK1. Collectively, these results demonstrate the importance of WNK1 ...

الإتاحة: https://doi.org/10.3389/fcell.2020.618898Test

المؤلفون: Martin-Vega, Ana, Earnest, Svetlana, Augustyn, Alexander, Wichaidit, Chonlarat, Gazdar, Adi, Girard, Luc, Peyton, Michael, Kollipara, Rahul K., Minna, John D., Johnson, Jane E., Cobb, Melanie H.

المصدر: bioRxiv

مصطلحات موضوعية: Article

الوصف: The transcription factor achaete-scute complex homolog 1 (ASCL1) is a lineage oncogene that is central for the growth and survival of small cell lung cancers (SCLC) and neuroendocrine non-small cell lung cancers (NSCLC-NE) that express it. Targeting ASCL1, or its downstream pathways, remains a challenge. However, a potential clue to overcoming this challenage has been information that SCLC and NSCLC-NE that express ASCL1 exhibit extremely low ERK1/2 activity, and efforts to increase ERK1/2 activity lead to inhibition of SCLC growth and surival. Of course, this is in dramatic contrast to the majority of NSCLCs where high activity of the ERK pathway plays a major role in cancer pathogenesis. A major knowledge gap is defining the mechanism(s) underlying the low ERK1/2 activity in SCLC, determining if ERK1/2 activity and ASCL1 function are inter-related, and if manipulating ERK1/2 activity provides a new therapeutic strategy for SCLC. We first found that expression of ERK signaling and ASCL1 have an inverse relationship in NE lung cancers: knocking down ASCL1 in SCLCs and NE-NSCLCs increased active ERK1/2, while inhibition of residual SCLC/NSCLC-NE ERK1/2 activity with a MEK inhibitor increased ASCL1 expression. To determine the effects of ERK activity on expression of other genes, we obtained RNA-seq from ASCL1-expressing lung tumor cells treated with an ERK pathway MEK inhibitor and identified down-regulated genes (such as SPRY4, ETV5, DUSP6, SPRED1) that potentially could influence SCLC/NSCLC-NE tumor cell survival. This led us to discover that genes regulated by MEK inhibition suppress ERK activation and CHIP-seq demonstrated these are bound by ASCL1. In addition, SPRY4, DUSP6, SPRED1 are known suppressors of the ERK1/2 pathway, while ETV5 regulates DUSP6. Survival of NE lung tumors was inhibited by activation of ERK1/2 and a subset of ASCL1-high NE lung tumors expressed DUSP6. Because the dual specificity phosphatase 6 (DUSP6) is an ERK1/2-selective phosphatase that inactivates these kinases and has a pharmacologic inhibitor, we focused mechanistic studies on DUSP6. These studies showed: Inhibition of DUSP6 increased active ERK1/2, which accumulated in the nucleus; pharmacologic and genetic inhibition of DUSP6 affected proliferation and survival of ASCL1-high NE lung cancers; and that knockout of DUSP6 “cured” some SCLCs while in others resistance rapidly developed indicating a bypass mechanism was activated. Thus, our findings fill this knowledge gap and indicate that combined expression of ASCL1, DUSP6 and low phospho-ERK1/2 identify some neuroendocrine lung cancers for which DUSP6 may be a therapeutic target.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::ef94a0bdbf60f3cbe21c93831e08f2fcTest
https://europepmc.org/articles/PMC10312738Test/

المؤلفون: Kankanamalage, Sachith Gallolu, Lee, A-Young, Wichaidit, Chonlarat, Lorente-Rodriguez, Andres, Shah, Akansha M., Stippec, Steve, Whitehurst, Angelique W., Cobb, Melanie H.

المصدر: Proceedings of the National Academy of Sciences of the United States of America, 2016 Dec . 113(50), 14342-14347.

الوصول الحر: https://www.jstor.org/stable/26472840Test

المؤلفون: Taylor, Clinton A., Cormier, Kevin W., Martin-Vega, Ana, Earnest, Svetlana, Stippec, Steve, Wichaidit, Chonlarat, Cobb, Melanie H.

المساهمون: Welch Foundation, National Institute of Diabetes and Digestive and Kidney Diseases, Mary Kay Foundation

المصدر: Biochemistry ; volume 62, issue 9, page 1433-1442 ; ISSN 0006-2960 1520-4995

مصطلحات موضوعية: Biochemistry

الإتاحة: https://doi.org/10.1021/acs.biochem.3c00044Test

المؤلفون: Gallolu Kankanamalage, Sachith, Lee, A-Young, Wichaidit, Chonlarat, Lorente-Rodriguez, Andres, Shah, Akansha M., Stippec, Steve, Whitehurst, Angelique W., Cobb, Melanie H.

المصدر: Autophagy ; volume 13, issue 5, page 969-970 ; ISSN 1554-8627 1554-8635

الإتاحة: https://doi.org/10.1080/15548627.2017.1286431Test

المؤلفون: Kalwat, Michael A., Wichaidit, Chonlarat, Nava Garcia, Alejandra Y., McCoy, Melissa K., McGlynn, Kathleen, Hwang, In Hyun, MacMillan, John B., Posner, Bruce A., Cobb, Melanie H.

المساهمون: Welch Foundation

المصدر: ACS Sensors ; volume 2, issue 2, page 316-316 ; ISSN 2379-3694 2379-3694

مصطلحات موضوعية: Fluid Flow and Transfer Processes, Process Chemistry and Technology, Instrumentation, Bioengineering

الإتاحة: https://doi.org/10.1021/acssensors.7b00012Test

المؤلفون: Barry, David M., Koo, Yeon, Norden, Pieter R., Wylie, Lyndsay A., Xu, Ke, Wichaidit, Chonlarat, Azizoglu, D. Berfin, Zheng, Yi, Cobb, Melanie H., Davis, George E., Cleaver, Ondine

المصدر: Circulation Research ; volume 119, issue 7, page 810-826 ; ISSN 0009-7330 1524-4571

الوصف: Rationale: Vascular tubulogenesis is essential to cardiovascular development. Within initial vascular cords of endothelial cells, apical membranes are established and become cleared of cell–cell junctions, thereby allowing continuous central lumens to open. Rasip1 (Ras-interacting protein 1) is required for apical junction clearance, as well as for regulation of Rho GTPase (enzyme that hydrolyzes GTP) activity. However, it remains unknown how activities of different Rho GTPases are coordinated by Rasip1 to direct tubulogenesis. Objective: The aim of this study is to determine the mechanisms downstream of Rasip1 that drive vascular tubulogenesis. Methods and Results: Using conditional mouse mutant models and pharmacological approaches, we dissect GTPase pathways downstream of Rasip1. We show that clearance of endothelial cell apical junctions during vascular tubulogenesis depends on Rasip1, as well as the GTPase Cdc42 (cell division control protein 42 homolog) and the kinase Pak4 (serine/threonine-protein kinase 4). Genetic deletion of Rasip1 or Cdc42, or inhibition of Pak4, all blocks endothelial cell tubulogenesis. By contrast, inactivation of RhoA (Ras homologue gene family member A) signaling leads to vessel overexpansion, implicating actomyosin contractility in control of lumen diameter. Interestingly, blocking activity of NMII (nonmuscle myosin II) either before, or after, lumen morphogenesis results in dramatically different tubulogenesis phenotypes, suggesting time-dependent roles. Conclusions: Rasip1 controls different pools of GTPases, which in turn regulate different pools of NMII to coordinate junction clearance (remodeling) and actomyosin contractility during vascular tubulogenesis. Rasip1 promotes activity of Cdc42 to activate Pak4, which in turn activates NMII, clearing apical junctions. Once lumens open, Rasip1 suppresses actomyosin contractility via inhibition of RhoA by Arhgap29, allowing controlled expansion of vessel lumens during embryonic growth. These findings elucidate the stepwise ...

الإتاحة: https://doi.org/10.1161/circresaha.116.309094Test

المؤلفون: Jaykumar, Ankita B., Plumber, Sakina, Barry, David M., Binns, Derk, Wichaidit, Chonlarat, Grzemska, Magdalena, Earnest, Svetlana, Goldsmith, Elizabeth J., Cleaver, Ondine, Cobb, Melanie H.

المصدر: Proceedings of the National Academy of Sciences of the United States of America; 7/26/2022, Vol. 119 Issue 30, p1-12, 12p

مصطلحات موضوعية: CELL junctions, ENDOTHELIAL cells, NEOVASCULARIZATION, PROTEIN-tyrosine kinases, TIGHT junctions

مستخلص: Angiogenesis is essential for growth of new blood vessels, remodeling existing vessels, and repair of damaged vessels, and these require reorganization of endothelial cell–cell junctions through a partial endothelial–mesenchymal transition. Homozygous disruption of the gene encoding the protein kinase WNK1 results in lethality in mice near embryonic day (E) 12 due to impaired angiogenesis. This angiogenesis defect can be rescued by endothelial-specific expression of an activated form of the WNK1 substrate kinase OSR1. We show that inhibition of WNK1 kinase activity not only prevents sprouting of endothelial cells from aortic slices but also vessel extension in inhibitor treated embryos ex vivo. Mutations affecting TGF-β signaling also result in abnormal vascular development beginning by E10 and, ultimately, embryonic lethality. Previously, we demonstrated cross-talk of WNK1 with TGF-β–regulated SMAD signaling, and OSR1 was identified as a component of the TGF-β interactome. However, molecular events jointly regulated by TGF-β and WNK1/OSR1 have not been delineated. Here, we show that inhibition of WNK1 promotes TGF-β–dependent degradation of the tyrosine kinase receptor AXL, which is involved in TGF-β–mediated cell migration and angiogenesis. We also show that interaction between OSR1 and occludin, a protein associated with endothelial tight junctions, is an essential step to enable tight junction turnover. Furthermore, we show that these phenomena are WNK1 dependent, and sensitive to TGF-β. These findings demonstrate intimate connections between WNK1/OSR1 and multiple TGF-β–sensitive molecules controlling angiogenesis and suggest that WNK1 may modulate many TGF-β–regulated functions. [ABSTRACT FROM AUTHOR]

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