Andre Ghetti

Andre Ghetti
AnaBios Corporation

PhD

About

76
Publications
8,862
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
1,842
Citations
Additional affiliations
June 2013 - present
AnaBios Corporation
Position
  • Executive
June 2011 - May 2013
AnaBios Corporation
Position
  • Principal Investigator
May 2004 - May 2011
AVIVA BioSciences
AVIVA BioSciences
Position
  • CEO

Publications

Publications (76)
Article
Full-text available
Glial cells are an integral part of functional communication in the brain. Here we show that astrocytes contribute to the fast dynamics of neural circuits that underlie normal cognitive behaviors. In particular, we found that the selective expression of tetanus neurotoxin (TeNT) in astrocytes significantly reduced the duration of carbachol-induced...
Article
Biological differences in sensory processing between human and model organisms may present significant obstacles to translational approaches in treating chronic pain. To better understand the physiology of human sensory neurons, we performed whole-cell patch-clamp recordings from 141 human dorsal root ganglion (hDRG) neurons from five young adult d...
Article
Full-text available
Ion channels are important therapeutic targets for the treatment of a variety of conditions. Among ion channel blocking agents, use-dependent inhibitors can be especially effective therapeutic agents. Use dependence allows the selective inhibition of hyperactive neurons or tachycardiac myocytes, while minimizing effects on cells with normal activit...
Preprint
The voltage-gated sodium NaV1.7 channel plays a key role as a mediator of action potential propagation in C-fiber nociceptors and is an established molecular target for pain therapy. ProTx-II is a potent and moderately selective peptide toxin from tarantula venom that inhibits human NaV1.7 activation. Here we used available structural and experimen...
Article
Full-text available
Late sodium current (late INa) inhibition has been proposed to suppress the incidence of arrhythmias generated by pathological states or induced by drugs. However, the role of late INa in the human heart is still poorly understood. We therefore investigated the role of this conductance in arrhythmias using adult primary cardiomyocytes and tissues f...
Article
Chronic pain is a disabling disease with limited treatment options. While animal models have revealed important aspects of pain neurobiology, therapeutic translation of this knowledge requires our understanding of these cells and networks of pain in humans. We propose a multi-institutional collaboration to rigorously and ethically address this chal...
Article
Full-text available
Substantial efforts have been recently committed to develop COVID-19 medications, and Hydroxychloroquine alone or in combination with Azithromycin has been promoted as a repurposed treatment. While these drugs may increase cardiac toxicity risk, cardiomyocyte mechanisms underlying this risk remain poorly understood in humans. Therefore, we evaluate...
Article
Full-text available
Background and purpose: The lack of selective sodium-calcium exchanger (NCX) inhibitors has hampered the exploration of physiological and pathophysiological roles of cardiac NCX 1.1. We aimed to discover more potent and selective drug like NCX 1.1. inhibitor. Experimental approach: A flavan series-based pharmacophore model was constructed. Virtu...
Article
Full-text available
Effects of non-cardiac drugs on cardiac contractility can lead to serious adverse events. Furthermore, programs aimed at treating heart failure have had limited success and this therapeutic area remains a major unmet medical need. The challenges in assessing drug effect on cardiac contractility point to the fundamental translational value of the cu...
Article
In preclinical drug development, accurate prediction of drug effects on the human heart is critically important, whether in the context of cardiovascular safety or for the purpose of modulating cardiac function to treat heart disease. Current strategies have significant limitations, whereby cardiotoxic drugs can escape detection or, potential life-...
Article
Full-text available
Itch induces scratching that removes irritants from the skin, whereas pain initiates withdrawal or avoidance of tissue damage. Whilst pain arises from both the skin and viscera, we investigated whether pruritogenic irritant mechanisms also function within visceral pathways. We show that subsets of colon-innervating sensory neurons in mice express,...
Article
The incomplete understanding of chronic neuropathic and inflammatory pain mechanisms poses a major challenge for the development of new, non-addictive pain medications. Cross-species differences in pharmacological responses and analgesic effects lead to poor translation of preclinical animal models to clinical studies in humans. We have developed m...
Article
Full-text available
Irritable bowel syndrome (IBS) patients suffer from chronic abdominal pain and extraintestinal comorbidities, including overactive bladder (OAB) and interstitial cystitis/painful bladder syndrome (IC-PBS). Mechanistic understanding of the cause and time course of these comorbid symptoms is lacking, as are clinical treatments. Here, we report that c...
Article
Background: T helper type 2 cell-released interleukin 31 (IL-31) is a critical mediator in atopic dermatitis (AD), a prevalent and debilitating chronic skin disorder. Brain-derived natriuretic peptide (BNP) has been described as a central itch mediator. The importance of BNP in peripheral (skin-derived) itch and its functional link to IL-31 within...
Article
Full-text available
To assess drug-induced pro-arrhythmic risk, especially Torsades de Pointe (TdP), new models have been proposed, such as in-silico modeling of ventricular action potential (AP) and stem cell-derived cardiomyocytes (SC-CMs). Previously we evaluated the electrophysiological profile of 15 reference drugs in hESC-CMs and hiPSC-CMs for their effects on i...
Article
Full-text available
Multiphoton microscopy using laser sources in the mid-infrared range (MIR, 1,300 nm and 1,700 nm) was used to image atherosclerotic plaques from murine and human samples. Third harmonic generation (THG) from atherosclerotic plaques revealed morphological details of cellular and extracellular lipid deposits. Simultaneous nonlinear optical signals fr...
Article
Full-text available
Cardiac safety remains the leading cause of drug development discontinuation. We developed a human cardiomyocyte-based model that has the potential to provide a predictive preclinical approach for simultaneously predicting drug-induced inotropic and pro-arrhythmia risk. Methods: Adult human primary cardiomyocytes from ethically consented organ dono...
Article
Full-text available
Background:In silico modeling could soon become a mainstream method of pro-arrhythmic risk assessment in drug development. However, a lack of human-specific data and appropriate modeling techniques has previously prevented quantitative comparison of drug effects between in silico models and recordings from human cardiac preparations. Here, we direc...
Article
While current S7B/E14 guidelines have succeeded in protecting patients from QT-prolonging drugs, the absence of a predictive paradigm identifying pro-arrhythmic risks has limited the development of valuable drug programs. We investigated if a human ex-vivo action potential (AP)-based model could provide a more predictive approach for assessing pro-...
Article
Both biomedical research and clinical practice rely on complex datasets for the physiological and genetic characterization of human hearts in health and disease. Given the complexity and variety of approaches and recordings, there is now growing recognition of the need to embed computational methods in cardiovascular medicine and science for analys...
Article
Full-text available
Scientific studies in drug development and toxicology rely heavily on animal models, which often inaccurately predict the true response for human exposure. This may lead to unanticipated adverse effects or misidentified risks that result in, for example, drug candidate elimination. The utilization of human cells and tissues for in vitro physiologic...
Article
We introduce a strategy for preclinical research wherein promising targets for analgesia are tested in rodent and subsequently validated in human sensory neurons. Here, we evaluate group II metabotropic glutamate receptors, the activation of which is efficacious in rodent models of pain. Immunohistochemical analysis showed positive immunoreactivity...
Article
While current S7B/E14 guidelines have succeeded in protecting patients from QT-prolonging drugs, the absence of a predictive paradigm identifying pro-arrhythmic risks has limited the development of valuable drug programs. We investigated if a human ex-vivo action potential (AP)-based model could provide a more predictive approach for assessing pro-...
Article
Full-text available
Both biomedical research and clinical practice rely on complex datasets for the physiological and genetic characterization of human hearts in health and disease. Given the complexity and variety of approaches and recordings, there is now growing recognition of the need to embed computational methods in cardiovascular medicine and science for analys...
Article
Full-text available
Peripheral neuropathy is dose limiting in paclitaxel cancer chemotherapy and can result in both acute pain during treatment and chronic persistent pain in cancer survivors. The hypothesis tested was that paclitaxel produces these adverse effects at least in part by sensitizing transient receptor potential vanilloid subtype 1 (TRPV1) through Toll-li...
Patent
Provided are methods and compositions for isolating and detecting rare cells from a biological sample containing other types of cells, particularly including debulking that uses a microfabricated filter for filtering samples. The enriched rare cells can be used in a downstream process such as identification, characterization or growth in culture, o...
Article
LLNL has demonstrated simultaneous fluorescence optical imaging and electrophysiological cell signal recording of dissociated human and rat dorsal root ganglia (DRG) nerve cells using a microfabricated in vitro chip-based human investigational platform (iCHIP) device. Both human and rat DRGs on the iCHIP devices after 16 days in vitro are physiolog...
Article
The flow cytometric analysis of leukocytes in whole blood usually requires isolation of leukocytes from other components of whole blood. Density gradient centrifugation and red blood cell lysis are the most commonly used methods to separate leukocytes but come with significant limitations. We report the results of the evaluation of a microfabricate...
Conference Paper
Full-text available
Glial cells have been thought to serve homeostatic functions in the brain. However, recent reports have suggested a potential role for astrocytes in neurotransmission. Various neurotransmitter receptors are expressed in astrocytes, allowing these cells to respond to exogenously applied neurotransmitters or neuronal stimulation with an increase in c...
Article
Full-text available
The voltage-clamp electrophysiology method is the gold standard for measuring the function of ion channels. In the past, this technique has had limited applicability in pharmaceutical drug discovery because of its low throughput, steep learning curve, and challenges in standardization of the experiments. Recently, new electrophysiology platforms ha...
Article
Full-text available
Unintended inhibition of the cardiac potassium channel human ether-a-go-go-related gene (hERG) is considered the main culprit in drug-induced arrhythmias known as torsades de pointes. Electrophysiology is the most reliable in vitro screening method for identifying potential cardiac hERG liabilities, but only the recent advent of planar electrode-ba...
Conference Paper
Full-text available
Glial cells have traditionally been assigned homeostatic functions in the brain. Recent reports, however, have highlighted the potential role for glia in neurotransmission. Various neurotransmitter receptors are expressed in astrocytes, allowing these cells to respond to exogenously applied neurotransmitters or neuronal stimulation with an increase...
Article
Full-text available
Dysiherbaine (DH) is a marine sponge-derived amino acid that causes seizures upon injection into mice. In this report we investigate the behavioral effects and characterize the pharmacological activity of DH. DH induced convulsive behaviors in mice with ED(50) values of 13 pmol/mouse, i.c.v. and 0.97 mg/kg, i.p. In rat brain synaptic membranes DH d...
Article
The ionotropic glutamate receptor subunit GluR6 undergoes developmentally and regionally regulated Q/R site RNA editing that reduces the calcium permeability of GluR6-containing kainate receptors. To investigate the functional significance of this editing in vivo, we engineered mice deficient in GluR6 Q/R site editing. In these mutant mice but not...
Article
Full-text available
Neurotransmitter receptor function can be influenced by the phosphorylation state of the receptor or of associated proteins. Here we show that kainate receptors expressed in cultured hippocampal neurons can be modulated by Ca(2+)/calmodulin-dependent phosphatase (calcineurin) and Ca(2+)/calmodulin-dependent kinase (CaMK). Ca(2+) influx through NMDA...
Article
Full-text available
The interactions established at the 5'-splice site during spliceosome assembly are likely to be important for both precise recognition of the upstream intron boundary and for positioning this site in the active center of the spliceosome. Definition of the RNA-RNA and the RNA-protein interactions at the 5' splice site would be facilitated by the use...
Article
Full-text available
Prp24 was previously isolated as a suppressor of a cold-sensitive U4 mutation and is required for at least the first step of splicing in vitro. Our investigation of the in vitro RNA binding properties of the purified Prp24 protein shows that it binds preferentially to the U4/U6 hybrid snRNAs compared to other snRNAs. The interaction between Prp24 a...