| 159 | Jessica Tanis, Ph.D. | <p>Assistant Professor <br></p> | (302) 831-8439 | | jtanis@udel.edu | 233 Wolf Hall | | | <ul>
<li>B.S. – Muhlenberg College
</li><li>Ph.D. – Yale University
</li><li>Postdoctoral – Yale University
</li><li>Postdoctoral – University of Pennsylvania Perelman School of Medicine<br> </li></ul> | | <p>Calcium homeostasis modulator 1 (CALHM1) is an ion channel expressed
in the brain and taste buds that plays important roles in cultured
cortical neuron excitability and taste perception. Human genetic studies
suggest that the P86L polymorphism in CALHM1 accelerates late onset
Alzheimer’s disease onset, however, the physiological significance of
CALHM1 activation in the mammalian brain remains unclear. CALHM1 and its
<em>C. elegans</em> homolog, CLHM-1, exhibit similar biophysical properties when expressed in <em>Xenopus</em> oocytes and functional conservation when expressed in <em>C. elegans</em>. We are utilizing the anatomical simplicity, genetic tools, and easily quantifiable behaviors of <em>C. elegans</em> to define CLHM-1 function.</p><p><strong>Our study of <em>C. elegans</em> CLHM-1 has resulted in the development of diverse projects</strong>.
Using a combination of genetic, imaging, behavioral,
electrophysiological, and biochemical approaches members of my lab are
seeking to 1) understand mechanisms underlying extracellular vesicle
formation and cargo sorting, 2) identify regulators of CLHM-1 function,
3) understand the role of diet in amyloid-beta toxicity, 4) characterize
novel factors that regulate signaling at the neuromuscular junction,
and 5) develop novel genetic methods / tools.<br></p> | <p><strong><img src="/content-sub-site/PublishingImages/people/jtanis/fig1.png" alt="Fig 1: Ciliated sensory neurons" class="ms-rtePosition-2" style="margin:5px;" />Identifying biogenesis and cargo sorting mechanisms for extracellular vesicle subpopulations</strong>
Extracellular vesicles (EVs) are membrane-wrapped structures that transfer bioactive macromolecules
between cells and play key roles in development and homeostasis as well
as the progression of pathological conditions including
neurodegenerative diseases and cancer. Remarkably, a single cell can
release multiple distinct EV subpopulations, each with different cargo
enrichment. <em>C. elegans</em> CLHM-1 is expressed in the IL2, CEM, HOB
and RnB sensory neurons and localizes to the cilia from which EVs are
released (Fig. 1). We discovered that animals expressing functional
GFP-tagged CLHM-1 at endogenous levels release CLHM-1::GFP in ciliary
derived EVs. <img src="/content-sub-site/PublishingImages/people/jtanis/fig2.png" class="ms-rtePosition-2" alt="Fig 2: CLHM-1" style="margin:5px;" />Analysis of animals expressing both tdTomato-tagged CLHM-1
and GFP-tagged PKD-2, a known cargo in EVs released from the same
ciliated sensory neurons, showed that the two fluorescent proteins do not colocalize in EVs (Fig. 2). Our goal is to use strengths of the <em>C. elegans</em> system to define EV biogenesis mechanisms and understand how EV cargo sorting specificity is achieved.
 </p><p><strong>Identification of CALHM channel regulators</strong>
We are also utilizing the powerful <em>C. elegans</em> model to gain
critical insights into cellular CALHM channel function. Our goal is to
identify and characterize CLHM-1 regulators in order to determine the
molecular mechanisms that control channel localization and function. We
have isolated CLHM-1 regulators in <em>C. elegans</em> by performing an
unbiased forward genetic screen for suppressors of toxicity associated
with CLHM-1 over-expression. After identifying the causative mutations
by a whole genome sequencing strategy, we will characterize the mutants
using genetic, behavioral and cell biological approaches.</p><p><strong>Impact of Diet on Amyloid-beta Toxicity in <em>C. elegans</em></strong>
We use a <em>C. elegans</em> model of Alzheimer’s disease (AD) to
identify factors that impact Aβ toxicity, a causative factor in AD
pathogenesis. Expression of human Aβ1-42 in <em>C. elegans</em>
causes fully penetrant, age-dependent paralysis. We found that loss of
CLHM-1 had no effect on Aβ toxicity, however, while conducting these
experiments we discovered that the type of <em>E. coli</em> diet that
Aβ-expressing animals consume alters paralysis rate. Our goal is to
determine how diet affects Aβ levels, mitochondrial morphology,
mitochondrial function, and gene expression in Aβ-expressing <em>C. elegans</em>.</p><p><strong>Characterization of novel regulators of post-synaptic signaling at the NMJ</strong>
<em>C. elegans</em> body-wall muscles are comparable to vertebrate
skeletal muscles and provide an excellent model to study neuromuscular
transmission. To identify novel factors that regulate post-synaptic
cholinergic signaling we carried out a genome wide RNAi screen in <em>C. elegans</em>
for gene knockdowns that cause hypersensitivity or resistance to the
AChR agonist levamisole. We discovered 156 gene knockdowns that caused
altered levamisole response. Our goal is to define the mechanism(s) by
which neuromuscular transmission is altered by determining how the gene
knockdowns affect locomotion, signaling, and synaptic structure using
biomechanical, optogenetic and imaging approaches. </p><p>
<strong><img src="/content-sub-site/PublishingImages/people/jtanis/fig3.png" class="ms-rtePosition-2" alt="Fig 3: Schematic of a superselective primer" style="margin:5px;" />A rapid, super-selective method for detection of single nucleotide variants</strong>
With
wide spread use of single nucleotide variants generated through
mutagenesis screens, the million mutation project, and genome editing
technologies there is pressing need for an efficient and low-cost
strategy to detect single nucleotide variants. We developed a rapid and
inexpensive method for detection of single nucleotide variants by
adapting superselective primers for end-point PCR. Each superselective
primer contains an anchor, bridge, and foot with the last nucleotide in
the foot region determining specificity for the mutant allele versus
wild type (Fig. 3). We explored how length, stability and sequence
composition of each segment affected primer selectivity and developed
simple rules for primer design (manuscript in preparation). We have
demonstrated the utility of superselective primers for routine
genotyping, detection of genome editing events, and colony PCR to
identify successful site-directed mutagenesis constructs. Additional
ongoing projects in the lab are aimed at developing novel genetics
methods.<br></p> | <p><strong><img src="/content-sub-site/PublishingImages/people/jtanis/tanislab-group.png" alt="Tanis Lab" class="ms-rtePosition-2" style="margin:5px;" />Denis Touroutine </strong>Postdoc (MS Chemistry, Moscow State
University; PhD, University of Illinois - Chicago, laboratory of Janet
Richmond) EV biogenesis and cargo sorting; CLHM-1 regulators; novel
methods development</p><p><strong>Michael Clupper</strong> Graduate Student (BS, Penn State University) EV biogenesis and cargo sorting</p><p><strong>Andy Lam</strong> Graduate Student (BA, University of Delaware) Impact of diet on amyloid-beta toxicity; NMJ signaling</p><p><strong>Rachael Gill</strong> Graduate Student (BS, Liberty University) EV biogenesis and cargo sorting</p><p><strong>Jaclyn Littmann</strong> Undergraduate BS Biological Sciences major (University of Delaware) EV biogenesis and cargo sorting</p><p><strong>Charlotte Leslie</strong> Undergraduate BS Biological Sciences major (University of Delaware) Impact of diet on amyloid-beta toxicity</p><p><strong>Erin Smith</strong> Undergraduate BS Biological Sciences major (University of Delaware) NMJ signaling</p><p><strong>Elizabeth Whelahan</strong> Undergraduate BA Exercise Science major (University of Delaware) NMJ signaling</p><p><strong>Previous Group Members</strong></p><p><strong>Kirsten Kervin</strong> Graduate Student (BS Delaware State
University, MS University of Delaware) Impact of diet on amyloid-beta
toxicity; NMJ signaling. Current - Laboratory Technician II at WuXi
AppTec.</p><p><strong>Elaine Miller</strong> Research Associate (BS, University of
California – Davis) CLHM-1 regulators; NMJ signaling. Current – graduate
student at George Washington University.</p><p><strong>Shrey Patel</strong> Undergraduate Biological Sciences Major
(BA, University of Delaware) NMJ signaling. Current – medical student at
Drexel University College of Medicine.<br></p> | <p>Ma Z, Taruno A, Ohmoto M, Jyotaki M, Lim JC, Miyazaki H, Niisato N,
Marunaka Y, Lee RJ, Hoff H, Payne R, Demuro A, Parker I, Mitchell CH,
Henao-Mejia J, <strong>Tanis JE</strong>, Matsumoto I, Tordoff MG, Foskett JK. (2018)<a href="https://www.ncbi.nlm.nih.gov/pubmed/29681531"> CALHM3 Is Essential for Rapid Ion Channel-Mediated Purinergic Neurotransmission of GPCR-Mediated Tastes</a>. Neuron 98(3):547-561.e10. doi: 10.1016/j.neuron.2018.03.043. Epub 2018 Apr 19.</p><p>
<strong>Tanis JE</strong>, Ma Z, Foskett JK. (2017) <a href="https://www.ncbi.nlm.nih.gov/pubmed/28515089">The NH2 terminus regulates voltage-dependent gating of CALHM ion channels</a>. Am J Physiol Cell Physiol 313(2):C173-C186.</p><p>
Collins KM, Bode A, Fernandez RW, <strong>Tanis JE</strong>, Brewer JC, Creamer MS, Koelle MR. (2016) <a href="https://www.ncbi.nlm.nih.gov/pubmed/27849154">Activity of the <em>C. elegans</em> egg-laying behavior circuit is controlled by competing activation and feedback inhibition</a>. Elife e21126.</p><p>
Vais H, Mallilankaraman K, Mak DD, Hoff H, Payne R, <strong>Tanis JE</strong>, Foskett JK. (2016) <a href="http://www.ncbi.nlm.nih.gov/pubmed/26774479">EMRE Is a Matrix Ca2+ Sensor that Governs Gatekeeping of the Mitochondrial Ca2+ Uniporter</a>. Cell Rep. 14(3):403-10.</p><p>
Ma Z, <strong>Tanis JE</strong>, Taruno A, Foskett JK. (2015) <a href="http://www.ncbi.nlm.nih.gov/pubmed/26603282">Calcium homeostasis modulator (CALHM) ion channels</a>. Pflugers Arch. 468(3):395-403.</p><p>
Vais H, <strong>Tanis JE</strong>, Müller M, Payne R, Mallilankaraman K, Foskett JK. (2015) <a href="http://www.ncbi.nlm.nih.gov/pubmed/26445506">MCUR1, CCDC90A, Is a Regulator of the Mitochondrial Calcium Uniporter</a>. Cell Metab. 22(4):533-5.</p><p>
Vingtdeux V, <strong>Tanis JE</strong>, Chandakkar P, Zhao H, Dreses-Werringloer U, Campagne F, Foskett JK, Marambaud P. (2014) <a href="http://www.ncbi.nlm.nih.gov/pubmed/25386646">Effect of the CALHM1 G330D and R154H human variants on the control of cytosolic Ca2+ and Aβ levels</a>. PLoS One. 9(11):e112484.</p><p>
Krajacic P*, Pistilli EE*, <strong>Tanis JE*</strong>, Khurana TS, Lamitina ST. (2013) <a href="http://www.ncbi.nlm.nih.gov/pubmed/24244862">FER-1/Dysferlin promotes cholinergic signaling at the neuromuscular junction in <em>C. elegans</em> and mice</a>. Biol. Open 2(11):1245-52.</p><p>
<strong>Tanis JE</strong>, Ma Z, Krajacic P, He L, Foskett JK, Lamitina T. (2013) <a href="http://www.ncbi.nlm.nih.gov/pubmed/23884934">CLHM-1 is a functionally conserved and conditionally toxic Ca2+-permeable ion channel in Caenorhabditis elegans</a>. J. Neurosci. 33(30):12275-86.</p><p>
Somasekharan S, <strong>Tanis J</strong>, Forbush B. (2012) <a href="http://www.ncbi.nlm.nih.gov/pubmed/22437837">Loop
diuretic and ion-binding residues revealed by scanning mutagenesis of
transmembrane helix 3 (TM3) of Na-K-Cl cotransporter (NKCC1)</a>. J. Biol. Chem. 287(21):17308-17.</p><p>
<strong>Tanis JE</strong>, Bellemer A, Moresco JJ, Forbush B, Koelle MR. (2009) <a href="http://www.ncbi.nlm.nih.gov/pubmed/19675228">The
potassium chloride cotransporter KCC-2 coordinates development of
inhibitory neurotransmission and synapse structure in Caenorhabditis
elegans</a>. J. Neurosci. 29(32):9943-54.</p><p>
Rinehart J, Maksimova YD, <strong>Tanis JE</strong>, Stone KL, Hodson
CA, Zhang J, Risinger M, Pan W, Wu D, Colangelo CM, Forbush B, Joiner
CH, Gulcicek EE, Gallagher PG, Lifton RP. (2009) <a href="http://www.ncbi.nlm.nih.gov/pubmed/19665974">Sites of regulated phosphorylation that control K-Cl cotransporter activity</a>. Cell 138(3):525-36.</p><p>
<strong>Tanis JE</strong>, Moresco JJ, Lindquist RA, Koelle MR. (2008) <a href="http://www.ncbi.nlm.nih.gov/pubmed/18202365">Regulation
of serotonin biosynthesis by the G proteins Galphao and Galphaq
controls serotonin signaling in Caenorhabditis elegans</a>. Genetics 178(1):157-69.</p><br> | | | <img alt="" src="/Images%20Bios/Tanis_Jessica.jpg" style="BORDER:0px solid;" /> | |
