Current Pharmacology PhD Students
Yanaira Alonso (Neuroscience), Ferrario Lab
Currently working on the role of the reproductive cycle in modulating approach to food cues in female obesity-prone and obesity-resistant rats.
Veronica Beck (Neuroscience), Isom Lab
I am interested in studying intestinal and metabolic dysfunction in a Dravet model of epilepsy, as well as potential therapeutic effects of a ketogenic diet in this model.
Ian Chronis, Puthenveedu Lab
Amanda Davis (Bolles), Osawa Lab
Protein Quality Control by the Hsp70/Hsp90 Chaperone System and Deubiquitinating Enzymes
Protein quality control is an essential process for the maintenance of cellular function. Proteins can be damaged as a result of disease or exposure to exogenous toxins. Damaged proteins must be selectively degraded to prevent their accumulation that, if left unchecked, can lead to cellular dysfunction. The Osawa lab has utilized mechanism based inactivators to damage neuronal nitric oxide synthase (nNOS) in order to study how the cell selectively culls damaged proteins for degradation. We have found that the heat shock protein 70 and 90 (Hsp70/90) chaperones recognize damaged nNOS and selectively triage the damaged protein for ubiquitination and proteasomal degradation. Through a series of studies investigating the role of the Hsp70/90 chaperones in the regulation of nNOS ubiquitination we have demonstrated that Hsp70 and Hsp90 play opposing roles in the regulation of client protein degradation. Hsp70 and its co-chaperone CHIP (c-terminus of Hsp70 interacting protein) ubiquitinates damaged protein and tags it for proteasomal degradation whereas Hsp90 stabilizes damaged protein and prevents degradation. We have applied the knowledge gained in these studies to develop new therapeutic strategies in neurodegenerative disease by enhancing the degradation of misfolded Hsp70/90 client proteins. In collaboration with the lab of Dr. Andrew Lieberman we demonstrated that activation of Hsp70 reduces neurotoxicity in a Drosophila model of spinal bulbar muscular atrophy. As part of these studies I am currently working to identify the role of deubiquitinating enzymes (DUBs) in the regulation of nNOS ubiquitination. Inhibition of DUBs responsible for nNOS deubiquitination may offer a new therapeutic strategy to enhance the selective degradation of nNOS. Preliminary studies have demonstrated that inhibition of DUBs by WP1130 increases nNOS ubiquitination in HEK293T cells. In order to identify DUBs capable of cleaving nNOS ubiquitin conjugates an in vitro purified protein DUB screen was utilized. Eleven DUBs capable of deubiquitinating nNOS were identified the majority of which were members of the ubiquitin specific protease subclass. These results suggest that DUBs play a role in the regulation nNOS ubiquitination.
Allie Bouza, Isom Lab
Gwendolyn Burgess, Jutkiewicz lab
Neikelyn Burgos, Rotating: Auchus Lab
Naincy Chandan, Smrcka Lab
Song Chen, Parent Lab
Stephanie Crilly (Cellular & Molec Biology), Puthenveedu Lab
Cara D'Amico, Kennedy Lab
Nick Denomme, Isom Lab
Jean Rodriguez Diaz (Neuroscience), Jones K. Lab
Our research is focused on determining the role of NMDA receptors in network activity. In particular we are studying how NMDA receptor antagonism influences chemical induced oscillations.
Nnamdi Edokobi, Isom Lab
Dana Felker (Toxicology), Osawa Lab
Mirella Hernandez (Neuroscience), Jones K. Lab
Caroline Hernadez-Casner, Puthenveedu Lab
Nichelle Jackson, Jones K. Lab
Elizabeth Jaeckel, Birdsong Lab
Kelsey Kochan, Traynor Lab
Jenny Kunselman (Cell & Molecular Biology), Puthenveedu Lab
Zesen "Jason" Lin, Khoriaty/Shayman Lab
Investigation of the function and importance of Syt-7 in exocytosis by FTIR microscopy and patch clamping.
Joshua Lott, Puthenveedu Lab
Alina Morales, Anantharam Lab
Loyda Morales Rodriguez, Puthenveedu Lab
Andrea Pesch, Speers/Rae Lab
Julie Philippe, Jenkins Lab
Zhuoying Ren, Anantharam Lab
Gissell Sanchez, Smrcka Lab
Jaquelyn Sanchez, Cohen Lab
My project focuses on inhibiting function of Hsp90 — a molecular chaperone responsible for the proteostasis of over 400 “client” proteins in eukaryotic cells — to overcome difficult-to-treat drug resistant melanomas. Our novel inhibitors target the carboxy terminus (C-terminal) of the chaperone decreasing adverse effects that plague all other Hsp90 inhibitors tested in clinical trials. We hypothesize that C-terminal inhibition of Hsp90 will simultaneously inhibit resistance pathways to rescue these drug resistant melanomas.
Bryan Sears, Jutkiewicz Lab
Rachel Springsdorf, Ferrario Lab
Ben Thompson, Satin Lab
Chiamaka Ukachukwu, Jones D. Lab
Juan Valentin-Goyco, Smrcka Lab
Nicholas Wagner, Traynor Lab
XiaoXue Zhang, Satin Lab
INVESTIGATING THE ROLE OF ER STRESS ON BETA CELL FUNCTION IN MOUSE PANCREATIC ISLETS
Type 2 diabetes mellitus (T2DM) is characterized by impaired glucose-stimulated insulin secretion and insulin resistance. Insulin is secreted from pancreatic beta-cells in response to a rise in plasma glucose in a pulsatile manner that is driven by Ca2+ oscillations. The endoplasmic reticulum (ER) is known to be one of the important Ca2+ sequestering and releasing organelle in the beta cell. Although it is well accepted that maintaining ER homeostasis is critical to proper beta cell function, the specific effects of ER stress and dysfunction on beta cell function are not completely understood. To determine the interrelationship between ER stress and intracellular free Ca2+ in pancreatic beta cells, we treated insulin-secreting INS-1 cells or isolated mouse islets with tunicamycin (TM; 10μg/ml) or DMSO as a control. Cytosolic Ca2+ was measured by loading islets with the Ca2+ sensing dye FURA2 and imaging its fluorescence using spectrofluorimetry. ER Ca2+ was measured using a novel, genetically-encoded FRET probe (D4ER). Treating islets for 16 hours with TM reduced ER Ca2+. To measure ER stress, levels of xbp1 mRNA splicing and BiP protein were measured by qPCR and immunoblotting. XBP1s and BiP levels started to increase after 6 hours and 12hours of TM treatment, respectively. Furthermore, PARP cleavage, a marker of initiation of apoptotic death, was observed after 12 hours of TM treatment by immunoblotting. We are continuing to fully delineate the effects of ER stress on insulin exocytosis and investigate the mechanism which ER stress occurs prior to ER Ca2+ reduction.
Yang Zhao, Chen Lab