- Crystal Archer, Ph.D.
- Allison Doyle Brackley, Ph.D.
- Chase Carver, Ph.D.
- Marlene Garcia, Ph.D.
- Nathan Mitchell, Ph.D.
- Jeremy Stubblefield, Ph.D.
- Desiree Wilson, 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.
Research Activities: Dr. Carver joined the Department of Physiology at the UTHSCSA as a postdoctoral researcher under the supervision of Dr. Mark S. Shapiro in Fall 2015. His focus has been to study voltage-gated ion channel physiology and correlated neurological dysfunction in determining heretofore unknown mechanisms of epileptogenesis in the hippocampus. The aim of his current research is to investigate “M-type” (KCNQ) K+ channels in hyperexcitability, since KCNQ2/3 channels are responsible for M-current to maintain homeostatic control over the neuronal resting membrane potential and firing frequency. Dr. Carver is currently investigating the interaction of muscarinic acetylcholilne receptors and M-channels in the dentate gyrus using electrophysiology and super resolution microscopy. He formed a hypothesis that in dentate gyrus granule cells, increased muscarinic actylcholine receptor activity at the axon initial segment results in greater seizure susceptibility via depression of M-current. This study will be tested by molecular expression, neuronal imaging, electrophysiology, and behavioral studies in mice. He is using novel transgenic tools in order to investigate mechanistic modulation of activities that originate in the dentate gyrus.
In the above studies, Dr. Carver is receiving training in new technical expertise as follows:
- Total Internal Reflective Fluorescence Microscopy and Imaging
- Super Resolution STORM Imaging
- Immunocytochemistry and Immunohistochemistry using heterologous expression systems
- DREADD (Drug Receptor Exclusively Activated by Designer Drug) delivery in vivo for molecular expression and pharmacological assays
2015 San Antonio Postdoctoral Research Forum, UTHSCSA, San Antonio, TX 2015 American Epilepsy Society, Annual Meeting, Philadelphia, PA
2016 San Antonio Postdoctoral Research Forum, UTHSCSA, San Antonio, TX
September 2015 Perimenstrual Upregulation of δ-subunit GABAA Receptors Mediating Tonic Inhibition and Neurosteroid Sensitivity. San Antonio Postdoctoral Research Forum. UTHSCSA
December 2015 Role of Tonic and M Currents in the Hippocampal Dentate Gyrus in Controlling Neuronal Excitability and Seizure Susceptibility. American Epilepsy Society, Annual Meeting, Philadelphia, PA (platform presentation) Carver CM, Shapiro MS. Parsing the necessary network components of the hippocampus in temporal lobe epileptogenesis. 5th Annual Cellular and Integrative Physiology Graduate Student Symposium. San Antonio, TX, April 7, 2017. Poster Presentation.
April 7, 2017 Carver CM, Shapiro MS. Parsing the necessary network components of the hippocampus in temporal lobe epileptogenesis. 5th Annual Cellular and Integrative Physiology Graduate Student Symposium. San Antonio, TX,. Oral Presentation.
April 7, 2017 Cook ME, Carver CM, Shapiro MS. M-type potassium channels are upregulated in the hippocampus in response to seizure activity. 5th Annual Cellular and Integrative Physiology Graduate Student Symposium. San Antonio, TX, April 7, 2017. Poster Presentation.
December, 2016 Carver CM, Shapiro MS. Maladaptive suppression of KCNQ/M-channel current by muscarinic acetylcholine receptor activation promotes epileptiform activity originating in the dentate gyrus. American Epilepsy Society Annual Meeting, Houston, TX,. Poster Presentation
September, 2016. Carver CM, Shapiro MS. Selective Activation of Muscarinic Receptors in Dentate Gyrus-CA3 Promotes Hyperexcitability and Seizure Susceptibility. Society of General Physiologists, Woods Hole, MA, Poster Presentation
2015 – American Epilepsy Society Postdoctoral Fellow, American Epilepsy Society
- 2012-pres – Society for Neuroscience
- 2014-pres – American Epilepsy Society
Coursework/Workshops: Dr. Carver actively participated in workshops during the Fall 2015 / Spring 2016 that included:
Spotlight on Research Integrity (workshop)
Dr. Garcia has recently completed her cardiology fellowship at UT Health San Antonio and is currently enrolled in the postdoctoral research program. She graduated from UT Southwestern Medical Center and completed her internal medicine residency there as well. Dr. Garcia’s prior experience has been mostly regarding community-based research. As her training progressed, she has developed an appreciation for clinical research in interventional cardiology, particularly as it relates to peripheral vascular disease and health disparities in the Hispanic community. Dr. Garcia is currently evaluating geographic trends and multivariate predictors regarding non-traumatic amputations in the state of Texas. In addition to this, she is actively involved in an epidemiologic study regarding subclinical lower extremity peripheral arterial disease in Mexican Americans in South Texas.
Research Activities: Innovative research efforts will combine Dr. Mitchell’s prior investigations in the development of novel anti-depressant drug efficacy via the function and ontogeny of organic cation transporters to examine the poorly understood comorbidity between cardiovascular diseases such as arterial hypertension and mood disorders such as depression. In Dr. Toney’s laboratory, he will explore the neurobiological underpinnings of this comorbidity using new skills that include in vivo single neuron recording and patch clamp electrophysiology in brain slices. These research efforts will address the hypothesis that high salt intake is a critical link between depression and salt-sensitive hypertension; according to this hypothesis, hyperexcitability and hyperactivity of sympathetic and mood controlling neurons will have common molecular triggers, including IL-17a which is a potent inducer of microglial activation. It is anticipated that as microglia become activated, foci of neuroinflammation gradually spread and disrupt mechanisms that maintain synaptic homeostasis. Because synaptic mechanisms that control sympathetic activity and those that control mood are different, the hypothesis is that common components within the proinflammatory milieu of sympathetic and mood controlling brain regions will nevertheless induce distinct cellular responses such that synaptic adaptations among pro-hypertensive neurons will be largely distinct from those that lead to depression. These studies will employ a well-established animal model of salt-sensitive hypertension.
Nathan C. Mitchell, Lee T. Gilman, Lynette C. Daws and Glenn M. Toney. Salt loading Activates Microglia and Increases Grooming Time and Time Spent Mobile in the Forced Swim Test: Is High Salt Intake a Causal Factor Linking Hypertension and Anxiety? Abstract, 4/24/17 Experimental Biology Annual Meeting
Mitchell, N.C., Bowman, M., Gould, G.G., Koek, W., Daws, L; Ontogeny of NET expression and antidepressant-like response to desipramine in wild-type and SERT mutant mice; The Journal of Pharmacology and Experimental Therapeutics 360; 84-94; PMID: 27831486: PMCID: PMC5193070
Koek, W., Mitchell, N.C., and Daws, L.C. (2017) Biphasic effects of selective serotonin reuptake inhibitors on anxiety: rapid reversal of escitalopram’s anxiogenic effects in the novelty-induced hypophagia (NIH) test in mice? Behav. Pharmacol. (In press).
April, 2017 “Salt loading Activates Microglia and Increases Grooming Time and Time Spent Mobile in the Forced Swim Test: Is High Salt Intake a Causal Factor Linking Hypertension and Anxiety?” Oral Presentation, Cell & Integrative Physiology Student Research Symposium
April, 2017 “Salt loading Activates Microglia and Increases Grooming Time and Time Spent Mobile in the Forced Swim Test: Is High Salt Intake a Causal Factor Linking Hypertension and Anxiety?” Poster Presentation, Experimental Biology 2017
May 2017 “Identifying Causal Factor(s) that Link Mood Disorder and Hypertension (…and Sleep Apnea).” Oral Presentation. University of North Texas Health Science Center at Fort Worth Hosted by Steve Mifflin
Dr. Stubblefield is conducting research in the laboratory of Dr. James Lechleiter. Broadly, the Lechleiter lab is interested in studying the neuroprotective role of thyroid hormone in stroke models. The Lechleiter lab has found that administration of thyroid hormone, 3,3,5 triido-L-thyronine (T3), to mice immediately following photothrombosis-induced stroke reduced stroke volume. T3 is also able to stimulate fatty-acid metabolism in astrocytes through binding and activation of Mitochondrial Trifunctional Protein (MTP). Dr. Stubblefield will be studying the molecular mechanisms of MTP activation in response to T3 administration both in vitro with primary murine astrocytes and in vivo with mice.
Interestingly, mortality from stroke follows a circadian pattern with a stronger probability of mortality occurring in the morning hours between 10 AM – 12 PM. Additionally, both Thyroid Stimulating Hormone (TSH) (the precursor to T3) and T3 oscillate in the circulation. Through his research, Dr. Stubblefield will examine whether the neuroprotective role of T3 in stroke severity also follows a circadian rhythm. He will use molecular, biochemical, and optical techniques to examine rhythmic metabolic processes within astrocytes to better understand their physiology in response to T3.
September 2017 – San Antonio Postdoctoral Research Forum
October 2017 – IIMS Community Engagement Symposium
April 2018 – Texas Society for Circadian Biology and Medicine Conference
May 2018 – Society for Research on Biological Rhythms Conference
F-Troop (Grantsmanship workshop) (planned, Fall 2017)
Responsible Conduct of Research Course (planned, Spring 2018)
Society for Research on Biological Rhythms, 2016-Present
Research Activities: Dr. Wilson’s postdoctoral training focuses on developing predictive models of surgical outcomes in frail patients with cardiovascular disease. Frailty is characterized as diminished physiological reserves and is more common in elderly populations. Greater than half of all surgeries in the United States are performed on patients > 65 years old, a demographic that will increase by 20.2% by 2050. Frail individuals are more likely to experience post-operative complications and co-morbidities. Identifying frail individuals prior to operative procedures would allow patients and clinicians to develop optimal treatment plans that minimize detrimental post-operative outcomes, time to recovery, and 30-day readmission rates. The Administrative Risk Analysis Index (RAI-A) is a measure of frailty that has been validated for use in predictive models for adverse post-operative outcomes. Minorities and patients in the low socioeconomic strata experience more co-morbidities. Including ethnicity, social risk factors and frailty (RAI-A) into a surgical outcome model will improve the predictive accuracy of the model beyond using RAI-A alone. The overall hypothesis is ethnicity, social risk factors and additional clinical variables such as grip strength will lead to improved accuracy in predicting adverse outcomes in patients prior to surgical procedures. To test this hypothesis, Dr. Wilson will utilize clinical information in electronic medical records (EMRs) and registry data obtained from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) and Veterans Affairs Surgical Quality Improvement Program (VASQIP) databases using the following aims:
Specific Aim 1: Determine the association of ethnicity and socioeconomic status on the effectiveness of RAI-A scores in predicting post-operative morbidity and mortality
Hypothesis 1A: RAI-A scores will predict similar morbidity and mortality in Hispanic and Caucasian populations
Hypothesis 1B: RAI-A scores will predict increased morbidity and mortality rates in frail patients with low socioeconomic status compared to middle and high socioeconomic status.
Specific Aim 2: Determine the association of RAI-A scores in predicting 30 day post-operative morbidity and mortality for vascular and cardiovascular procedures based upon type of surgery performed and emergency versus elective procedures
Hypothesis: RAI-A scores associated with increased morbidity and mortality will be associated with emergency events and surgical procedures that enter the thoracic and abdominal cavities
Specific Aim 3: Implement RAI and grip strength screening in Vascular Surgery clinics at the STVHCS and UHS
Hypothesis: The combination of RAI frailty screening and grip strength, a physical measure of muscle strength, will better predict postoperative morbidity and mortality than either measure alone
Dr. Wilson’s goal is to become an independent clinical informatics researcher utilizing EMRs and precision medicine to improve patient care. Understanding how data is obtained during a research study is paramount as the collection process influences analysis and interpretation. Her postdoctoral fellowship with Paula Shireman, MD and Jon Gelfond, MD, PhD will provide Dr. Wilson with direct, hands-on clinical experience while working to improve surgical outcome prediction models. Having a deeper understanding of the clinical variables effecting surgical outcomes will lead to a more robust model, which in turn will optimize patient care and further the field of precision medicine.
August 23 – 25, 2017 – San Antonio Geriatric & Palliative Education (SAGE) Symposium, San Antonio, Texas
September 21, 2017 – San Antonio Postdoctoral Research Forum, San Antonio, Texas
August 2012 to current – Association for Computing Machinery (ACM)
Statistics with R Specialization
Applied Data Science with Python Specialization
Data Science Specialization
Oracle Database SQL Certifed Associate