- Crystal Archer, Ph.D.
- Allison Doyle Brackley, Ph.D.
- Elizabeth Gould, Ph.D.
- Tabita Kreko, Ph.D.
- Erica Littlejohn, Ph.D.
Crystal Archer (Mentors: J. Stockand and M. Shapiro) 07/01/2017-present
Dr. Archer’s interest in membrane proteins and ion channels brought her to UTHSCSA in 2011, where she applied biochemical chemical analyses and structural biology methods to improve the understanding of the molecular mechanism of a potassium ion channel. She earned her PhD in Biochemistry, in June 2017, and soon afterward, joined Dr. Jim Stockand’s laboratory at UTHSCSA as a postdoctoral researcher. Her current focus is to understand the molecular mechanism of how minor plasma membrane phospholipids regulate ENaC (Epithelial Na+ Channel) function. ENaC is an ion channel that is critical for the transport of Na+ and filtered fluid reabsorption through the epithelial lining of many tissues, such as the lungs and kidney. Evidence suggests that, similar other ion channels, the phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2), prevents the decrease of ENaC open probability, and phosphatidylinositol 3,4,5-bisphosphate (PIP3) further enhances the basal levels of ENaC current. However, the details of the structural and molecular mechanism of how these phospholipids affect ENaC function are still unclear. ENaC is a tetrameric protein, comprised of an alpha, beta and gamma subunit. The Stockand Lab used mutagenesis to show that the amino terminus of the beta and gamma subunits contain sites rich in basic residues that may directly bind to these phospholipids. The goal of my research is to determine the sites of the ENaC subunits that bind these phospholipids and elucidate their biochemical affinities, in an effort to gain structural evidence on how these phospholipids influence the gating of ENaC.
Dr. Brackley is currently working on two primary research projects in Dr. Toney’s laboratory. The first aims to investigate neural mechanisms involved in sodium-induced cross-sensitization of reward systems and seeking behaviors. Salt is perhaps the most frequently abused substance in modern society. Because emerging evidence implicates the endogenous opioid system in salt appetite and need-free sodium intake, an unmet need exists for the identification of opioid-mediated mechanisms that prime reward circuits to support salt addiction. This project will use the primal need that mammals have for salt as a novel means to access and reinforce the circuit elements, as well as neurochemical and synaptic mechanisms, that promote addiction and seeking behavior for a variety of rewarding substances, especially illicit drugs.
The second aims to investigate the neurocircuitry that underlies the propagation of sleep apnea-related opioid-induced respiratory depression. There is an important interrelationship between opioids, sleep apnea, and overdose. Given that chronic opioid use dose-dependently increases sleep apnea in humans and that sleep apnea increases opioid sensitivity, patients with sleep apnea have a high risk in the clinic for opioid-induced respiratory depression and subsequent overdose. Thus, an unmet need exists to identify the neurocircuitry that underlies the propagation of sleep apnea-related opioid-induced respiratory complications. Understanding these neurochemical and synaptic mechanisms may lead to identification of safer therapeutic options for this patient population. Dr. Brackley’s projects involve concurrent slice patch-clamp electrophysiology and Ca2+ imaging, optogenetics, nerve recordings, in vivo electrophysiology, microinjections, viral transduction, neuroanatomical methods, and integrative whole animal approaches.
Click here to see Dr. Brackley’s online CV.
Elizabeth Gould, PhD (Mentor: J. Kim) 09/01/2018-present
Dr. Gould earned her PhD in Neuroscience from the University of Colorado, Denver in August 2017, where she studied the role of oligodendrocytes, the myelin-producing cell in the central nervous system, in neural circuit function. As a postdoctoral researcher in Dr. Jun Hee Kim’s lab, Dr. Gould continues to study oligodendrocytes and how they modulate neural function through bi-directional communication. Neuronal activity shapes oligodendrocyte development and myelination; however, the cellular and molecular mechanisms through which this occurs are currently unknown. The first aim of Dr. Gould’s work is to understand how oligodendrocyte excitability modulates their response to neuronal activity. The second aim of Dr. Gould’s work focuses on how oligodendrocytes influence neuronal activity by modulating synapse function. Bi-directional signaling between oligodendrocytes is essential for neural circuit development and function. To study the cellular and molecular mechanisms of neuron-oligodendrocyte communication, Dr. Gould utilizes a combination of genetic models, electrophysiology, Ca2+-imaging, immunohistochemistry, and behavioral testing.
Tabita Kreko, PhD (Mentor: J. Pugh) 10/01/2017-present
Dr. Kreko-Pierce earned her PhD in Physiology at UTHSCSA in June 2017, where she studied mechanisms that underlie axonal transport of proteasomes and aging of the neuromuscular junction. Soon after, she joined the laboratory of Dr. Jason Pugh at UTHSCSA where she is currently conducting her postdoctoral research. Her research focuses on the role of the protein dystrophin on the function of neurons in the cerebellum and hippocampus. In skeletal muscle dystrophin is a key component of the multiprotein dystroglycan complex that acts as a linker between the intracellular cytoskeleton and the extracellular matrix, thus mediating the structural stability of the plasma membrane. Mutations in the dystrophin gene cause a common human condition known as muscular dystrophy. In addition to its expression in muscle tissue, dystrophin is also highly expressed in the central nervous system, particularly in neurons of the hippocampus and cerebellum; however, the role of this protein in the CNS remains largely unknown. Interestingly, many individuals with muscular dystrophy display severe cognitive deficits, suggesting the role of dystrophin in normal neuronal function. Dr. Kreko-Pierce’s hypothesis is that dystrophin mutations disrupt cerebellar and hippocampal function which contributes to the loss of motor and cognitive function observed in muscular dystrophy patients. She will test this hypothesis using a combination of genetics (cell specific knock-out animals), patch-clamp electrophysiology, immunohistochemistry and behavioral testing.
Tabita Kreko-Pierce and Benjamin A. Eaton. (2018) Rejuvenation of the aged neuromuscular junctionby exercise. Cell Stress Volume , Issue , pp.
Erica Littlejohn, PhD (Mentor: C. Boychuk) 09/01/2018-present
Dr. Littlejohn is interested in harnessing endogenous repair mechanisms to reduce the burden of disease(s) caused by dysregulation of the central nervous system. Dr. Littlejohn completed her dissertation in May 2018 at the University of Kentucky. She investigated cellular and molecular mechanisms underlying neural plasticity in the hippocampus influencing recovery from traumatic brain injury.
Dr. Littlejohn joined the lab of Dr. Carie Boychuk in August 2018. Her training in Dr. Boychuk’s lab will equip her to use sophisticated electrophysiological techniques to investigate the functional consequences of neural plasticity in the CNS. Parasympathetic drive is critical to the maintenance of whole-body homeostasis and normal physiological organ function. In states of energy homeostatic dysfunction, like obesity, parasympathetic drive is reduced. Parasympathetic output is generated through motor neurons localized in the brain stem whose axons course through the vagus nerve. The set of these preganglionic motor neurons originating in the dorsal motor nucleus of the vagus (DMV) are implicated in diabetic parasympathetic dysregulation since DMV neurons send axonal projections to nearly all subdiaphragmatic viscera important in metabolism. Dr. Boychuk recently showed that in models of energy homeostatic dysfunction like chronic hyperglycemia/hypoinsulinemia, DMV neurons demonstrate significant plasticity, particularly in GABAA receptor function. However, the mechanism of this functional upregulation are currently unknown, making targetable treatment options difficult to assess. One potential target is a secondary, endogenous ligand to the GABA receptor, the neurosteroid derivative of progesterone, allopregnanolone. Interestingly, allopregnanolone has been implicated in estrous cycle modulation of GABAA receptor function as well, making it critically important to understand how these currents work in female, both in health and disease. In Dr. Boychuk’s lab, Dr. Littlejohn will employ obesity models, and to a larger extent diabetes models to investigate the role neurosteroids play in hyperglycemia after high-fat diet on GABAergic regulation of the DMV and glucose metabolism in females.