Kevin E Fogarty

Kevin E Fogarty
University of Massachusetts Medical School | UMMS · Program in Molecular Medicine

About

197
Publications
27,310
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11,929
Citations
Additional affiliations
July 2007 - present
University of Massachusetts Medical School
April 1999 - May 1999
University of Cambridge
April 1997 - June 2007

Publications

Publications (197)
Preprint
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We present new, deep, narrow- and broad-band Hubble Space Telescope observations of seven of the most star-forming brightest cluster galaxies (BCGs). Continuum-subtracted [O II] maps reveal the detailed, complex structure of warm ($T \sim 10^4$ K) ionized gas filaments in these BCGs, allowing us to measure spatially-resolved star formation rates (S...
Article
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Context: Rapid on-site evaluation (ROSE) optimizes the performance of cytology, but requires skilled handling, and smearing can make the material unavailable for some ancillary tests. There is a need to facilitate ROSE without sacrificing part of the sample. Objective: We evaluated the image quality of inexpensive deconvolution fluorescence micr...
Article
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For quality, interpretation, reproducibility and sharing value, microscopy images should be accompanied by detailed descriptions of the conditions that were used to produce them. Micro-Meta App is an intuitive, highly interoperable, open-source software tool that was developed in the context of the 4D Nucleome (4DN) consortium and is designed to fa...
Article
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For the information content of microscopy images to be appropriately interpreted, reproduced, and meet FAIR (Findable Accessible Interoperable and Reusable) principles, they should be accompanied by detailed descriptions of microscope hardware, image acquisition settings, image pixel and dimensional structure, and instrument performance. Nonetheles...
Preprint
Full-text available
For the information content of microscopy images to be appropriately interpreted, reproduced, and meet FAIR (Findable Accessible Interoperable and Reusable) principles, they should be accompanied by detailed descriptions of microscope hardware, image acquisition settings, image pixel, and dimensional structure, and instrument performance. Nonethele...
Article
A persistent basal tone in the internal anal sphincter (IAS) is essential for keeping the anal canal closed and fecal continence; its inhibition via the rectoanal inhibitory reflex (RAIR) is required for successful defecation. However, cellular signals underlying the IAS basal tone remain enigmatic. Here we report the origin and molecular mechanism...
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Small-molecule fluorescent wheat germ agglutinin (WGA) conjugates are routinely used to demarcate mammalian plasma membranes, because they bind to the cell's glycocalyx. Here, we describe the derivatization of WGA with a pH-sensitive rhodamine fluorophore (pHRho; pKa = 7) to detect proton channel fluxes and extracellular proton accumulation and dep...
Preprint
Full-text available
Small molecule fluorescent wheat germ agglutinin (WGA) conjugates are routinely used to demarcate mammalian plasma membranes because they bind to the cell's glycocalyx. Here we describe the derivatization of WGA with a pH sensitive rhodamine fluorophore (pHRho: pKa = 7) to detect proton channel fluxes and extracellular proton accumulation and deple...
Article
We present new Atacama Large Millimeter Array observations of the molecular gas and far-infrared continuum around the brightest cluster galaxy (BCG) in the cool-core cluster MACS 1931.8-2635. Our observations reveal (1.9 ± 0.3) × 10^(10) M⊙ of molecular gas, on par with the largest known reservoirs of cold gas in a cluster core. We detect CO(1−0),...
Article
Ion channels in myometrial cells play critical roles in spontaneous and agonist-induced uterine contraction during the menstrual cycle, pregnancy maintenance and parturition; thus identifying the genes of ion channels in these cells and determining their roles are essential to understanding the biology of reproduction. Previous studies with in vitr...
Preprint
We present new ALMA observations of the molecular gas and far-infrared continuum around the brightest cluster galaxy (BCG) in the cool-core cluster MACS 1931.8-2635. Our observations reveal $1.9 \pm 0.3 \times 10^{10}$ M$_{\odot}$ of molecular gas, on par with the largest known reservoirs of cold gas in a cluster core. We detect CO(1-0), CO(3-2), a...
Article
We investigate the evolution of star formation rates (SFRs), stellar masses, and M/L_3.4 micron ratios of brightest cluster galaxies (BCGs) in the COSMOS survey since z ~ 1 to determine the contribution of star formation to the growth-rate of BCG stellar mass over time. Through the spectral energy distribution (SED) fitting of the GALEX, CFHT, Suba...
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Full-text available
Presynaptic reuptake, mediated by the dopamine (DA) transporter (DAT), terminates DAergic neurotransmission and constrains extracellular DA levels. Addictive and therapeutic psychostimulants inhibit DA reuptake and multiple DAT coding variants have been reported in patients with neuropsychiatric disorders. These findings underscore that DAT is crit...
Article
Preterm birth (PTB) is the leading cause of neonatal mortality and morbidity, with few prevention and treatment options. Uterine contraction is a central feature of PTB, so gaining new insights into the mechanisms of this contraction and consequently identifying novel targets for tocolytics are essential for more successful management of PTB. Here...
Article
We study the nature of the feedback mechanism required to offset cooling in the 11 CLASH brightest cluster galaxies (BCGs) that exhibit extended ultraviolet and nebular line emission features. We estimate star formation rates (SFRs), dust masses, and starburst durations using a Bayesian SED fitting technique that accounts for both stellar and dust...
Article
Cells use plasma membrane proton fluxes to maintain cytoplasmic and extracellular pH and to mediate the co-transport of metabolites and ions. Because proton-coupled transport often involves movement of multiple substrates, traditional electrical measurements provide limited information about proton transport at the cell surface. Here we visualize v...
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siRNAs are a new class of therapeutic modalities with promising clinical efficacy that requires modification or formulation for delivery to the tissue and cell of interest. Conjugation of siRNAs to lipophilic groups supports efficient cellular uptake by a mechanism that is not well characterized. Here we study the mechanism of internalization of as...
Article
Full-text available
Smooth muscle sphincters exhibit basal tone and control passage of contents through organs such as the gastrointestinal tract; loss of this tone leads to disorders such as faecal incontinence. However, the molecular mechanisms underlying this tone remain unknown. Here, we show that deletion of myosin light-chain kinases (MLCK) in the smooth muscle...
Data
Supplementary Figures 1-17, Supplementary Tables 1-2 and Supplementary References
Article
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The assembly and maintenance of most cilia and flagella rely on intraflagellar transport (IFT). Recentin vitrostudies have suggested that the calponin-homology domain in the IFT81 N-terminus and the highly basic N-terminus of IFT74 together form a module for IFT of tubulin. UsingChlamydomonasmutants for IFT81 and IFT74, we have tested this hypothes...
Article
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The dopamine (DA) transporter (DAT) facilitates high-affinity presynaptic DA reuptake that temporally and spatially constrains DA neurotransmission. Aberrant DAT function is implicated in attention-deficit/hyperactivity disorder and autism spectrum disorder. DAT is a major psychostimulant target, and psychostimulant reward strictly requires binding...
Article
The CLASH X-ray selected sample of 20 galaxy clusters contains ten brightest cluster galaxies (BCGs) that exhibit significant ($>$5 $\sigma$) extinction-corrected star formation rates (SFRs). Star formation activity is inferred from photometric estimates of UV and H$\alpha$+[NII] emission in knots and filaments detected in CLASH HST observations. T...
Article
Full-text available
Brightest cluster galaxies (BCGs) are usually quiescent, but many exhibit star formation. Here we exploit the opportunity provided by rest-frame UV imaging of galaxy clusters in the CLASH (Cluster Lensing and Supernovae with Hubble) Multi-Cycle Treasury Project to reveal the diversity of UV morphologies in BCGs and to compare them with recent simul...
Article
Beclin 1 is a haploinsufficient tumor suppressor that is decreased in many human tumors. The function of beclin 1 in cancer has been attributed primarily to its role in the degradative process of macroautophagy. However, beclin 1 is a core component of the vacuolar protein sorting 34 (Vps34)/class III phosphatidylinositoI-3 kinase (PI3KC3) and Vps1...
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Background We report a 6.5 year-old female with a homozygous missense mutation in ZFYVE20, encoding Rabenosyn-5 (Rbsn-5), a highly conserved multi-domain protein implicated in receptor-mediated endocytosis. The clinical presentation includes intractable seizures, developmental delay, microcephaly, dysostosis, osteopenia, craniofacial dysmorphism, m...
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The protein nephrocystin-4 (NPHP4) is widespread in ciliated organisms, and defects in NPHP4 cause nephronophthisis and blindness in humans. To learn more about NPHP4's function, we have studied it in Chlamydomonas reinhardtii. NPHP4 is stably incorporated into the distal part of the flagellar transition zone, close to the membrane and distal to CE...
Article
Adrenal chromaffin cells (ACCs), stimulated by the splanchnic nerve, generate action potentials (AP) at a frequency near 0.5 Hz in the resting physiological state, at times described as “rest and digest.” How such low frequency stimulation in turn elicits sufficient catecholamine exocytosis to set basal sympathetic tone is not readily explained by...
Article
Focus stabilization is critical for many imaging modalities like TIRF, PALM and STORM. The focus stabilization device presented here, named pgFocus, is an open source and open hardware solution that can be integrated into microscopes with an existing objective positioner. pgFocus is a programmable and inexpensive circuit board consisting of a micro...
Article
Full-text available
Dopaminergic signaling profoundly impacts rewarding behaviors, movement, and executive function. The presynaptic dopamine (DA) transporter (DAT) recaptures released DA, thereby limiting synaptic DA availability and maintaining dopaminergic tone. DAT constitutively internalizes and PKC activation rapidly accelerates DAT endocytosis, resulting in DAT...
Article
Full-text available
Bronchodilators are a standard medicine for treating airway obstructive diseases, and β2 adrenergic receptor agonists have been the most commonly used bronchodilators since their discovery. Strikingly, activation of G-protein-coupled bitter taste receptors (TAS2Rs) in airway smooth muscle (ASM) causes a stronger bronchodilation in vitro and in vivo...
Data
Bronchodilators are a standard medicine for treating airway obstructive diseases, and b2 adrenergic receptor agonists have been the most commonly used bronchodilators since their discovery. Strikingly, activation of G-protein-coupled bitter taste receptors (TAS2Rs) in airway smooth muscle (ASM) causes a stronger bronchodilation in vitro and in vivo...
Data
Characteristics of [Ca2+]i and contractile responses to bitter tastants and diltiazem in human ASM. (A) Bitter tastants reversed the [Ca2+]i rise and cell shortening induced by Mch. Measurements were taken at the steady state levels in response to Mch and chloroquine. The cell length before stimulation was considered as 100%. *p<0.05 paired Student...
Data
KCl activates L-type VDCCs to increase [Ca2+]i and cause contraction in mouse ASM. (A) KCl failed to generate any global [Ca2+]i increase in the absence of extracellular Ca2+ in isolated single ASM cells. (i) A representative [Ca2+]i response to 60 mM KCl in the presence of extracellular Ca2+. (ii, iii, iv) three examples showing that the same conc...
Data
This clip shows 1 mM chloro reversed the 100 µM Mch-induced increase in [Ca2+]i and cell shortening; the first 120 images of this clip were analyzed and plotted in Figure 2A. The images are displayed as fluorescence intensity (rather than ΔF/F0) because the cell changes its shape dramatically in response to stimuli (and changing thickness makes ΔF/...
Data
Bitter tastant chloroquine dose-dependently increased [Ca2+]i in resting single cells (A) without a significant effect on the contractility (B) of relaxed mouse airways. Results are mean ± SEM, (n = 5–30 cells in (A) and 7 airway rings in (B)). Dose response curves in (A) were generated on the basis of the responses to single dose administration, w...
Data
KCl activates VDCCs in cholinergic nerves and ASM. (A) Atropine dose-dependently inhibited Mch-induced mouse airway contraction. The left panels display representative contractile responses to 3 µM Mch in the absence or the presence of atropine as marked near the traces, and the right panel shows the mean values (mean ± SEM; n = 4–8) of inhibition...
Data
Ca2+ influx plays a major role in producing and maintaining Mch-induced increases in [Ca2+]i and contraction in mouse ASM. (A) In Ca2+ free medium, the tension generated by Mch was less than 20% of that in the presence of extracellular Ca2+. ***p<0.001, Student's paired t-test, n = 9 airway rings for the group with Ca2+, and n = 10 airway rings for...
Data
Role of L-type Ca2+ channel activation in Mch-induced contraction in mouse airway. (A) Left panel: L-type VDCC blocker diltiazem dose-dependently reversed Mch-induced contraction (using tension as a proxy measure). Right panel: results for n = 6 airway rings. % relaxation was calculated the same as in Figure S2B. (B) Diltiazem inhibited Mch- and KC...
Data
Primers for Reverse Transcription-PCR. (TIFF)
Article
In addition to its role as a morphogen, Sonic hedgehog (Shh) has also been shown to function as a guidance factor that directly acts on the growth cones of various types of axons. However, the noncanonical signaling pathways that mediate the guidance effects of Shh protein remain poorly understood. We demonstrate that a novel signaling pathway cons...
Article
Full-text available
Cell surface receptors and other proteins internalize through diverse mechanisms at the plasma membrane and are sorted to different destinations. Different subpopulations of early endosomes have been described, raising the question of whether different internalization mechanisms deliver cargo into different subsets of early endosomes. To address th...
Article
Full-text available
The neuropilins (NRPs) contribute to the function of cancer cells in their capacity as VEGF receptors. Given that NRP2 is induced in breast cancer and correlates with aggressive disease, we examined the role of NRP2 in regulating the interaction of breast cancer cells with the ECM. Using epithelial cells from breast tumors, we defined NRP2(high) an...
Article
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The type 1 ryanodine receptor (RyR1) is expressed widely in the brain, with high levels in the cerebellum, hippocampus, and hypothalamus. We have shown that L-type Ca(2+) channels in terminals of hypothalamic magnocellular neurons are coupled to RyRs, as they are in skeletal muscle, allowing voltage-induced Ca(2+) release (VICaR) from internal Ca(2...
Article
Full-text available
Short-lived, localized Ca(2+) events mediate Ca(2+) signaling with high efficiency and great fidelity largely as a result of the close proximity between Ca(2+)-permeable ion channels and their molecular targets. However, in most cases, direct evidence of the spatial relationship between these two types of molecules is lacking, and, thus, mechanisti...
Article
Full-text available
Context.—Advances in microscopy enable visualization of a broad range of new morphologic features. Objective.—To review and illustrate advances in microscopy with relevance to pathologists. Data Sources.—Literature review and new observations. Results.—Fluorescence microscopy enables multiantigen detection; allows novel optical-sectioning technique...
Article
Full-text available
Advances in microscopy enable visualization of a broad range of new morphologic features. To review and illustrate advances in microscopy with relevance to pathologists. Literature review and new observations. Fluorescence microscopy enables multiantigen detection; allows novel optical-sectioning techniques, with some advantages compared to paraffi...
Article
Full-text available
Protein kinase B/Akt protein kinases control an array of diverse functions, including cell growth, survival, proliferation, and metabolism. We report here the identification of pleckstrin homology-like domain family B member 1 (PHLDB1) as an insulin-responsive protein that enhances Akt activation. PHLDB1 contains a pleckstrin homology domain, which...