Jessica Tanis, Ph.D.

Research Interests

Regulation of Ca2+ homeostasis is an essential cellular function controlled by diverse mechanisms. Disruption of neuronal Ca2+ homeostasis can occur following ischemic stroke, epileptic seizures and traumatic brain injury and has been linked to neurodegenerative diseases. However, the molecular mechanisms that underlie disruptions in cellular Ca2+ handling are not completely understood. Calcium homeostasis modulator 1 (CALHM1) is an ion channel regulated by voltage and extracellular Ca2+ that controls cytosolic Ca2+ levels. Human genetic studies suggest that the P86L polymorphism in CALHM1 accelerates the onset of late-onset Alzheimer’s disease. CALHM ion channels have also been shown to play important roles in cortical neuron excitability and taste perception in mice and locomotion in C. elegans. CALHM proteins have a unique pharmacological profile and lack sequence similarity with known channels, thus they belong to a new, evolutionarily conserved class of physiologically significant ion channels. Using a combination of genetic, cell biological, behavioral, electrophysiological and biochemical approaches my lab is 1) identifying the physiological functions of CALHM channels as well as mechanisms by which CALHM channels are regulated in vivo and 2) characterizing novel factors that regulate Ca2+ signaling at the neuromuscular junction.

Current Projects

Identification of CALHM channel regulators using C. elegans

Genetic redundancy and the multimeric structure of mammalian CALHM proteins complicates the analysis of CALHM1. We discovered that the sole C. elegans homolog, CLHM-1, and human CALHM1 exhibit similar biophysical properties when expressed in Xenopus oocytes and are functionally interchangeable when expressed in C. elegans. Thus, we can utilize the powerful model system C. elegans to gain critical insights into CALHM channel function in vivo. One of our primary goals is to identify and characterize CALHM regulators in order to determine the molecular mechanisms that control channel localization and function. We have isolated CLHM-1 regulators in C. elegans 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 and SNP mapping strategy, we will characterize the mutants using genetic, behavioral and cell biological approaches. This project is funded by an INBRE Pilot Project award.

Functional consequences of CALHM signaling in C. elegans sensory neurons

Since human CALHM1 is primarily expressed in neurons, understanding how CLHM-1 regulates the activity of C. elegans neurons could provide critical insight into conserved function in vivo. We have shown that CLHM-1 is expressed in the IL2, ASG, ASK, ASJ, PHA and PHB sensory neurons. Our goal is to determine if CLHM-1 signaling affects the function, Ca2+ transients and/or excitability of these neurons. We will use clhm-1 knockout worms and transgenic animals over-expressing CLHM-1 for behavioral analyses and in vivo Ca2+ imaging to further define the role(s) of CALHM channels in neurons. This project is funded by an INBRE Pilot Project award.

The role of CALHM proteins in mammalian taste perception

CALHM1 is expressed in type II taste cells which lack synapses and instead communicate with afferent nerves by action potential-dependent release of the neurotransmitter ATP. Calhm1 knockout mice cannot perceive sweet, bitter and umami tastants and exhibit defects in ATP release from type II taste cells, indicating that CALHM1 is an ATP release channel required for taste perception. Yet, how can the fast action potentials required for ATP release stimulate CALHM1 which has slow activation kinetics? We used a candidate gene approach and identified an interacting protein that confers fast kinetics to the CALHM1 channel. Our goal is to define the role of this novel regulator in taste perception and ATP release from type II taste cells. This project is funded by the National Institute on Deafness and other Communication Disorders.

Characterization of novel regulators of post-synaptic signaling at the NMJ

C. elegans body-wall muscles are comparable to vertebrate skeletal muscles and provide an excellent model in which to study neuromuscular transmission. To identify novel factors that regulate post-synaptic cholinergic signaling we carried out a genome wide RNAi screen in C. elegans for gene knockdowns that cause hypersensitivity or resistance to the AChR agonist levamisole. We discovered 156 gene knockdowns that caused altered levamisole response. We will 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. This work will lead to the characterization of novel molecular mechanisms of cholinergic signaling regulation.


Selected Publications

Assistant Professor

Phone: (302) 831-8439


Office: 233 Wolf Hall


  • B.S. – Muhlenberg College
  • Ph.D. – Yale University
  • Postdoctoral – Yale University
  • Postdoctoral – University of Pennsylvania Perelman School of Medicine