Yu-Hsin Chiu's research while affiliated with National Tsing Hua University and other places
What is this page?
This page lists the scientific contributions of an author, who either does not have a ResearchGate profile, or has not yet added these contributions to their profile.
It was automatically created by ResearchGate to create a record of this author's body of work. We create such pages to advance our goal of creating and maintaining the most comprehensive scientific repository possible. In doing so, we process publicly available (personal) data relating to the author as a member of the scientific community.
If you're a ResearchGate member, you can follow this page to keep up with this author's work.
If you are this author, and you don't want us to display this page anymore, please let us know.
It was automatically created by ResearchGate to create a record of this author's body of work. We create such pages to advance our goal of creating and maintaining the most comprehensive scientific repository possible. In doing so, we process publicly available (personal) data relating to the author as a member of the scientific community.
If you're a ResearchGate member, you can follow this page to keep up with this author's work.
If you are this author, and you don't want us to display this page anymore, please let us know.
Publications (45)
Growth differentiation factor 15 (GDF15) is a secreted protein that regulates food intake, body weight, and stress responses in pre-clinical models ¹ . The physiological function of GDF15 in humans remains unclear. Pharmacologically, GDF15 agonism in humans caused nausea without accompanying weight loss ² , and the effect of GDF15 antagonism is bei...
Discovery of new small molecules that can activate distinct programmed cell death pathway is of significant interest as a research tool and for the development of novel therapeutics for pathological conditions such as cancer and infectious diseases. The small molecule raptinal was discovered as a pro-apoptotic compound that can rapidly trigger apop...
Pannexin 1 (PANX1) is a widely expressed large-pore ion channel located in the plasma membrane of almost all vertebrate cells. It possesses a unique ability to act as a conduit for both inorganic ions (e.g. potassium or chloride) and bioactive metabolites (e.g. ATP or glutamate), thereby activating varying signaling pathways in an autocrine or para...
Extracellular purines, such as ATP, act as ligands of P2X and P2Y receptors to modulate many important physiologies. The discovery of multiple ATP-releasing plasma membrane ion channels, such as CALHM1 and Pannexin 1 (Panx1), presents previously unappreciated mechanisms to activate purinergic signaling pathways. Panx1 channels are widely expressed...
Activation of Pannexin 1 (PANX1) ion channels causes release of intercellular signaling molecules in a variety of (patho)physiological contexts. PANX1 can be activated by G protein-coupled receptors (GPCRs), including α1-adrenergic receptors (α1-ARs), but how receptor engagement leads to channel opening remains unclear. Here, we show that GPCR-medi...
Allergic airway inflammation is driven by type-2 CD4+ T cell inflammatory responses. We uncover an immunoregulatory role for the nucleotide release channel, Panx1, in T cell crosstalk during airway disease. Inverse correlations between Panx1 and asthmatics and our mouse models revealed the necessity, specificity, and sufficiency of Panx1 in T cells...
Pannexin 1 (Panx1) is a membrane channel implicated in numerous physiological and pathophysiological processes via its ability to support release of ATP and other cellular metabolites for local intercellular signaling. However, to date, there has been no direct demonstration of large molecule permeation via the Panx1 channel itself, and thus the pe...
Pannexin 1 (Panx1) channels are widely expressed and play important roles in apoptotic cell clearance, inflammation, blood pressure regulation, neurological disorders, opiate withdrawal, and cancer progression and metastasis. We performed (1) physicochemical analysis on a constitutively closed Panx1 channel (designated fPanx1ΔC) to examine the enti...
The serine protease Factor XI (FXI) is a prominent drug target as it holds promise to deliver efficacious anti-coagulation without an enhanced risk of major bleeds. Several efforts have been described targeting the active form of the enzyme, FXIa. Herein we disclose our efforts to identify potent, selective, and orally bioavailable inhibitors of FX...
The serine protease factor XI (FXI) is a prominent drug target as it holds promise to deliver efficacious anticoagulation without an enhanced risk of major bleeds. Several efforts have been described targeting the active form of the enzyme, FXIa. Herein, we disclose our efforts to identify potent, selective, and orally bioavailable inhibitors of FX...
A large unmet medical need exists for safer antithrombotic drugs because all currently approved anticoagulant agents interfere with hemostasis, leading to an increased risk of bleeding. Genetic and pharmacologic evidence in humans and animals suggests that reducing factor XI (FXI) levels has the potential to effectively prevent and treat thrombosis...
Using an unbiased screen for potential inhibitors of pannexin1 (Panx1) channels, we identified spironolactone, a potent anti‐hypertensive, as being able to block Panx1 channels. This was especially interesting considering spironolactone has been considered a mineralcorticoid receptor (MR) antagonist. Initial confirmation of this result was obtained...
Rationale:
Resistant hypertension is a major health concern with unknown cause. Spironolactone is an effective antihypertensive drug, especially for patients with resistant hypertension, and is considered by the World Health Organization as an essential medication. Although spironolactone can act at the mineralocorticoid receptor (MR; NR3C2), ther...
Pannexin 1 (Panx1) forms plasma membrane ion channels that are widely expressed throughout the body. Panx1 activation results in the release of nucleotides such as adenosine triphosphate and uridine triphosphate. Thus, these channels have been implicated in diverse physiological and pathological functions associated with purinergic signaling, such...
PARK2 is a gene implicated in disease states with opposing responses in cell fate determination, yet its contribution in pro-survival signaling is largely unknown. Here we show that PARK2 is altered in over a third of all human cancers, and its depletion results in enhanced phosphatidylinositol 3-kinase/Akt (PI3K/Akt) activation and increased vulne...
Neuropathic pain symptoms respond poorly to available therapeutics, with most treated patients reporting unrelieved pain and significant impairment in daily life. Here, we show that Pannexin 1 (Panx1) in hematopoietic cells is required for pain-like responses following nerve injury in mice, and a potential therapeutic target. Panx1 knockout mice (P...
Supplementary figures and Supplementary table.
Pannexin 1 (PANX1) subunits form oligomeric plasma membrane channels that mediate nucleotide release for purinergic signalling, which is involved in diverse physiological processes such as apoptosis, inflammation, blood pressure regulation, and cancer progression and metastasis. Here we explore the mechanistic basis for PANX1 activation by using wi...
Using a series of immunoprecipitation (IP) – tandem mass spectrometry (LC-MS/MS) experiments and reciprocal BLAST, we conducted a fly-human cross-species comparison of the phosphoinositide-3-kinase (PI3K) interactome in a drosophila S2R+ cell line and several NSCLC and human multiple myeloma cell lines to identify conserved interacting proteins to...
Objective:
Defective glucose uptake in adipocytes leads to impaired metabolic homeostasis and insulin resistance, hallmarks of type 2 diabetes. Extracellular ATP-derived nucleotides and nucleosides are important regulators of adipocyte function, but the pathway for controlled ATP release from adipocytes is unknown. Here, we investigated whether Pa...
Both purinergic signaling through nucleotides such as ATP (adenosine 5'-triphosphate) and noradrenergic signaling through molecules such as norepinephrine regulate vascular tone and blood pressure. Pannexin1 (Panx1), which forms large-pore, ATP-releasing channels, is present in vascular smooth muscle cells in peripheral blood vessels and participat...
Bromodomain-containing protein 7 (BRD7) is a member of the bromodomain-containing protein family that is known to play a role as tumor suppressors. Here, we show that BRD7 is a component of the unfolded protein response (UPR) signaling through its ability to regulate X-box binding protein 1 (XBP1) nuclear translocation. BRD7 interacts with the regu...
The innate immune system deploys a variety of sensors to detect signs of infection. Nucleic acids represent a major class of pathogen signatures that can trigger robust immune responses. The presence of DNA in the cytoplasm of mammalian cells is a danger signal that activates innate immune responses; however, how cytosolic DNA triggers these respon...
Plasma membrane pannexin 1 channels (PANX1) release nucleotide find-me signals from apoptotic cells to attract phagocytes. Here we show that the quinolone antibiotic trovafloxacin is a novel PANX1 inhibitor, by using a small-molecule screen. Although quinolones are widely used to treat bacterial infections, some quinolones have unexplained side eff...
Phosphoinositide 3-kinase (PI3K) activity is important for regulating cell growth, survival, and motility. We report here the identification of bromodomain-containing protein 7 (BRD7) as a p85α-interacting protein that negatively regulates PI3K signaling. BRD7 binds to the inter-SH2 (iSH2) domain of p85 through an evolutionarily conserved region lo...
Pannexin 1 (Panx1) channels are generally represented as non-selective, large-pore channels that release ATP. Emerging roles have been described for Panx1 in mediating purinergic signaling in the normal nervous, cardiovascular, and immune systems, where they may be activated by mechanical stress, ionotropic and metabotropic receptor signaling, and...
Pannexin 1 (PANX1) is a non-selective ion channel that mediates the uptake of cyanine dyes and release of nucleotides and other metabolites. PANX1 activation and ATP release/dye uptake are regulated by diverse stimuli, including physicochemical factors (e.g., stretch, K+ ions) and signaling by various G protein-coupled and ionotropic receptors. We...
We recently demonstrated that pannexin1 (Panx1) channels release ATP in vascular smooth muscle cells after phenylephrine (PE) stimulation (Billaud et al, Circ Res, 2011). However, the participation of Panx1 in other contractile pathways has not been investigated. Therefore, we stimulated thoracodorsal arteries with angiotensin II, endothelin‐1, ser...
Pannexin‐1 (PANX1) channels release ATP, a “find‐me” signal that recruits macrophages to apoptosing cells. Cleavage of the PANX1 C terminus by caspases represents a new mechanism of ion channel opening, but how the C terminus regulates channel activity is unclear. We provide evidence suggesting that the C terminal residues of PANX1 block the pore a...
Pannexin 1 (PANX1) channels mediate release of ATP, a "find-me" signal that recruits macrophages to apoptotic cells; PANX1 activation during apoptosis requires caspase-mediated cleavage of PANX1 at its C terminus, but how the C terminus inhibits basal channel activity is not understood. Here, we provide evidence suggesting that the C terminus inter...
RIG-I-like receptors (RLRs) activate host innate immune responses against virus infection through recruiting the mitochondrial adaptor protein MAVS (also known as IPS1, VISA, or CARDIF). Here we show that MAVS also plays a pivotal role in maintaining intestinal homeostasis. We found that MAVS knockout mice developed more severe mortality and morbid...
Class IA PI3Ks are activated by growth factor receptors and generate lipid second messengers that mediate downstream responses including cell growth, cell migration, and cell survival. The p85 regulatory subunit of PI3K contains Src homology-2 (SH2) domains that mediate binding to tyrosine-phosphorylated receptors or adaptor proteins to facilitate...
Type I interferons (IFNs) are important for antiviral and autoimmune responses. Retinoic acid-induced gene I (RIG-I) and mitochondrial antiviral signaling (MAVS) proteins mediate IFN production in response to cytosolic double-stranded RNA or single-stranded RNA containing 5'-triphosphate (5'-ppp). Cytosolic B form double-stranded DNA, such as poly(...
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
A study was conducted to understand the three steps of the NF-κB pathway, IκB degradation, processing of NF-κB precursors, and activation of IKK and other kinases. The study also highlighted how deubiquitination enzymes negatively regulate the NF-κB pathway and how dysfunction of these enzymes lead to human diseases. It was observed that NF-κB path...
Ubiquitination is catalyzed by a cascade of enzymes consisting of E1, E2, and E3. We report here the identification of an E1-like protein, termed E1-L2, that activates both ubiquitin and another ubiquitin-like protein, FAT10. Interestingly, E1-L2 can transfer ubiquitin to Ubc5 and Ubc13, but not Ubc3 and E2-25K, suggesting that E1-L2 may be special...
The activation of NF-kappaB and IKK requires an upstream kinase complex consisting of TAK1 and adaptor proteins such as TAB1, TAB2, or TAB3. TAK1 is in turn activated by TRAF6, a RING domain ubiquitin ligase that facilitates the synthesis of lysine 63-linked polyubiquitin chains. Here we present evidence that TAB2 and TAB3 are receptors that bind p...
Citations
... Asundexian (Fig. 1b), a potent dual inhibitor developed by Bayer, exhibits IC 50 values of 1 nM and 6.7 nM for FXIa and PKa, respectively [30]. Compound 1 (Fig. 1b), reported by Novartis group, contains a basic dihydrobenzofuran-3-amine fragment and demonstrates subnanomolar affinity for both FXIa and PKa [31]. Additionally, the pyridine macrocyclic milvexian (Fig. 1b), disclosed by the Bristol Myers Squibb group, exhibits low nanomolar potency against both FXIa and PKa [16]. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/272439640850456-1441966080523_Q64/Eva-Altmann.jpg)
... Src kinase is also involved in this process; however, it is unclear if PANX1 is a direct substrate of Src . In addition to tyrosine phosphorylation, murine PANX1 has been reported to undergo serine phosphorylation at Ser205 and Ser206, although two studies have shown contradictory effects of the two serine phosphorylation sites on PANX1 channel activity (Poornima et al., 2015;Medina et al., 2021). Likewise, the S394 of rat PANX1 could be phosphorylated by CaMKII upon an increase in cytoplasmic Ca 2+ concentration (López et al., 2021). ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/350023708626945-1460463563641_Q64/Christopher-Lucas-4.jpg)
![[object Object]](https://i1.rgstatic.net/ii/profile.image/272476399730701-1441974844475_Q64/Kodi-Ravichandran.jpg)
... In living cells, Panx1 is activated by a variety of stimuli including membrane stretch/shrinkage (14,15), voltage (16), increased concentrations of cations (14,17,18), posttranslational modifications (11,19), and stimulation of membrane receptors (20)(21)(22). Our group recently discovered that lysophospholipids, signaling molecules produced by lipolytic enzymes like phospholipase A2 (PLA2), directly and reversibly activate Panx1 (8). ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/761095144873988-1558470631584_Q64/Catherine-Doyle-2.jpg)
![[object Object]](https://i1.rgstatic.net/ii/profile.image/516107272036353-1500060970294_Q64/Douglas-Bayliss.jpg)
... In apoptotic cells, it is well-established that the Panx1 channel undergoes direct activation through caspase-mediated removal of the C-terminus (23,24). This channel-opening mechanism plays a crucial role in releasing cellular metabolites from dying cells, with a particular emphasis on ATP, which serves as a "find-me" signal for recruiting monocytes (10). ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/761754363629571-1558627801641_Q64/Alex-Kreutzberger.jpg)
![[object Object]](https://i1.rgstatic.net/ii/profile.image/277667820654595-1443212575445_Q64/Pablo-Gaete.jpg)
... To assess supposed antithrombotic activity of synthesized derivatives 4-8, we used the molecular docking method. The protease domain of coagulation factor XI(F11) in complex with an active site inhibitor (PDB identifier: 6TS4) [43] was chosen as the target protein. Three-dimensional (3D) structures were obtained from the RCSB Protein Data Bank [44], whereas the ligand molecules were sketched using ChemBio3D Ultra 14.0. ...
... In other words, abelacimab will neutralize the enzyme before entering the coagulation cascade. Single subcutaneous and intravenous administrations were safe and welltolerated, and suppressed FXI activity beyond 4 weeks [65,66]. Abelacimab significantly prolonged the time to circuit clotting ex vivo [67]. ...
... Pressure Myography of Cannulated Arteries. As described previously (45,66), third order mesenteric arteries were removed, cannulated, and pressurized to 60 mmHg. Arteries were washed with a Ca 2+ -free Krebs-Hepes solution to obtain maximal passive diameter of the vessels. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/664960107548672-1535550252640_Q64/Miranda-Good.jpg)
... Through an unbiased drug screening approach, we have previously identified the antibiotic trova and the anti-hypertensive spironolactone as new inhibitors of PANX1 [26,51]. Discovery of such properties of trova and spironolactone not only highlights the potential side effects of these drugs but also the opportunities to repurpose them to inhibit PANX1 in certain settings. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/279405449498628-1443626858341_Q64/Chris-Medina-2.jpg)
... While this observation suggests that the full-length Panx1 channel is in an active conformation, we propose that the channel activity is cell type dependent. In HEK293 cells, both our research and others' findings have shown that full-length Panx1 does not respond to activation stimuli (42). However, in other cell types such as tsA201 or HEK293S GnTIcells, this construct exhibits voltage-or lysophospholipid-dependent channel activity (8,29). ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/11431281123088634-1677635977899_Q64/Bimal-Desai-6.jpg)
... In the course of activated mitophagy facilitated by Parkin, the latter serves as a crucial mitophagy factor that effectively eradicates impaired mitochondria and their associated proteins, consequently mitigating the levels of ROS within the mitochondria 63 , although its effect may differ on certain occasions 9 . A study found that consuming Parkin could attenuate PD toxin-induced H 2 O 2 ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/411252590432259-1475061666822_Q64/Amit-Gupta-125.jpg)
![[object Object]](https://i1.rgstatic.net/ii/profile.image/903730337681411-1592477511654_Q64/Sara-Anjomani-Virmouni.jpg)
![[object Object]](https://i1.rgstatic.net/ii/profile.image/317566445129738-1452725148835_Q64/Nikos-Koundouros.jpg)
