Student Research
STUDENTS DESCRIBE THEIR RESEARCH PROJECTS
Dorinda Arch
The focus of my dissertation research is an evaluation of the role of hepatic ATP-binding cassette (ABC) transporters, inclusive of their regulation of expression and function, in hemochromatosis and the development and progression of porphyria cutanea tarda. This project utilizes genetic mouse models of the human diseases.
Sarah Campbell
My research involves analytical toxicology of a metabolite of benzo(a)pyrene (benzo(a)pyrene diol epoxide, BPDE) and whether BPDE-protein adducts can be used as a biomarker of tobacco smoke exposure. I will be developing a HPLC (detector still to be determined) method(s) and using a histological approach, determine if BPDE-protein adduct concentrations correlate to tissue toxicity.
Greg Hadlock
Methamphetamine is widely abused and is neurotoxic to dopaminergic neurons. Multiple high-dose administrations of methamphetamine causes a persistent decrease in the activity of the dopamine transporter, which clears dopamine from the extracellular space back into the neuron, and the formation of higher molecular weight dopamine transporter complexes. My research utilizes mass spectrometry, western blotting, enzymatic assays, and other techniques to elucidate the mechanisms underlying the dopamine transporter complex formation and decrease in activity following methamphetamine administration. I am particularly interested in oxidative stress pathways and the ubiquitin-proteasome system.
Fred Henion
Capsaicin is a mechanism-based inhibitor of cytochrome P450 2E1 (CYP2E1). I am using capsaicin (and analogs of capsaicin) as probes to investigate substrate structural features and the enzyme active site parameters that determine whether CYP2E1 will catalyze dehydrogenation vs. oxygenation reactions. The dehydrogenated products of P450 mediated metabolism are often reactive electrophilic intermediates that can cause toxicity by binding to cellular proteins or DNA.
Jason Little
My research studies the cardiac changes associated with status epilepticus and temporal lobe epilepsy. These cardiac changes are thought to be associated with sudden death or sudden unexplained death in epilepsy. Current studies include evaluating the effect of the Li-pilocarpine model of induced status epilepticus on cardiac myocyte damage and arrhythmogenesis.
Arlo McGinn
Mesenchymal stem cells are bone marrow-derived stem cells that have garnered interest lately for their ability to recover infarcted tissue in the heart post myocardial infarction when they are transplanted into damaged heart tissue. One of the major problems accompanying this surgical procedure is the low survival of implanted mesenchymal stem cells due to hypoxia-induced apoptosis after transplantation. I am looking to improve and extend transplanted mesenchymal stem cell viability by transfecting the stem cells with siRNA directed toward hypoxia-inducible proapoptotic proteins, using a polymeric gene delivery system. We hypothesize that knockdown of these proapoptotic proteins will result in more efficient and complete recovery of the damaged tissue than has been achieved in the past using traditional transplantation techniques.
Chad Moore
My research is currently focused on the formation of reactive intermediates during cytochrome P450 mediated reactions. Specifically, I’m interested the mechanisms that control cytochrome P450 dehydrogenation (desaturation) reactions. To learn more about these reactions, we are using raloxifene/CYP3A4 as a model substrate/enzyme pair to elucidate factors that control dehydrogenation reactions.
Robyn Poerschke
The Moos Lab has an interest in selenium and its role in cancer prevention and treatment. My project specifically is looking at several different selenium compounds and determining how they differentially affect parameters of cellular redox state, as well as the induction of genes regulated by the Nrf2 transcription factor, in a human lung adenocarcinoma and a “normal” human bronchial epithelial cell line. I will also be examining the role of two selenoproteins, thioredoxin reductase 1 and glutathione peroxidase 2, in the modulation of cellular redox state by the selenocompounds.
Przemyslaw Radwanski
My research project focuses on the role of regional ventricular heterogeneities in arrhythmogenesis.
Colleen Rock
The major goals of my research are to determine the transcriptional mechanism responsible for upregulation of Selenoprotein P and to evaluate the antioxidant function of the protein against lipid hydroperoxides. I use multiple molecular techniques for evaluating transcriptional regulation and protein expression, including luciferase reporter assays, quantitative PCR, and western blotting. Various cytometric assays are being used to study the antioxidant effect of Selenoprotein P. We hope that this work will continue to provide information regarding the mechanism by which supplemental selenium exerts a cancer chemopreventive effect.
Nicole Rowley
My research is testing if the betaine/GABA transporter (BGT1) plays an important role in the control of CNS excitability and seizures. Results will help define the importance and role of this transporter in epilepsy, as well as its usefulness as a therapeutic target for the development of novel GABA transport inhibitors
Kiumars Shahrokh
My research focuses on using both computational modeling and bioanalytical techniques to understand the structural, electronic and thermodynamic factors that contribute to P450-catalyzed dehydrogenation reactions.
Karen Thomas
The hypothesis of my work is that TRPV1 activation in lung cells initiates endoplasmic reticulum stress, cell death and acute lung injury in an animal model of septic lung injury. We have shown that TRPV1-mediated ER stress causes lung cell death through activation of the PERK pathway. Subsequent work has focused on understanding how structural features of capsaicinoids alter TRPV1 binding, activation, and cell death as a product of ER stress. The final goal of this work is to establish TRPV1 as a mediator of acute lung injury in a mouse model of sepsis.
Jay Vargas
Increasing evidence suggests that non-neuronal glial cells may contribute to seizure generation and epilepsy. My research seeks to identify changes to protein expression and cell function in astrocytes in an animal model of temporal lobe epilepsy. It is anticipated that this work will reveal new potential therapeutic targets for the treatment of epilepsy.
Jessica Weems
3-Methylindole (3MI) is a highly selective, prototypical pneumotoxicant present in cigarette smoke. Human cytochrome P450 (CYP450) enzymes have been shown to catalyze the dehydrogenation of 3MI to the reactive intermediate 3-methyleneindolenine (3MEIN). This intermediate has been shown to alkylate DNA, resulting in DNA damage. My project is focused on characterizing the relative potency of 3MI to induce mutagenic and pro-apoptotic processes in primary human lung cells.
STUDENT AWARDS
Fellowship Awards:
Jay Vargas has received a Fellowship Award from the Epilepsy Foundation (2007), Michael Koch has received a Pre-doctoral Fellow Award from the American Foundation for Pharmaceutical Education and Kiumars Shahrokh has received a University of Utah Graduate Research Fellowship (2008) College of Pharmacy Willard L. Eccles Foundation First Year Graduate Fellowships were awarded to Kiumars Shahrokh (2004), Robyn Poerschke (2005), Nicole Rowley (2006) and Arlo McGinn (2006)
Presentation Awards:
Colleen Rock was awarded the Postgraduate Best Paper Award in the area of Basic Sciences at the annual meeting for the American Pharmacists Association (2008). Karen Thomas was the Third Prize Recipient, of the Society of Toxicology Molecular Biology Specialty Section Graduate Student Award (2008). Jessica Weems was awarded second place in the Graduate Student and Postdoctoral Platform Presentation Session at the Western Pharmacology Society Annual Meeting (2005) and also second place in the student presentations of the Mountain-West Regional Chapter of the Society of Toxicology (2008).
Travel Awards:
Karen Thomas and Dori Arch (200) and Cassie Deering (2008) received Travel Awards from the Society of Toxicology to attend the Society’s annual meeting. Dori Arch and Kiumars Shahrokh have received travel awards from ASPET and the University of Utah. Robyn Poerschke has received a University of Utah Travel Award to attend the Society of Toxicology annual meeting in 2009. Jessica Weems and Karen Thomas have received Travel Awards from the Mountain West Regional Chapter of the Society of Toxicology (2006).
