Abstracts 2022
Here are the abstracts of all presentations for RID 2022!
#1
Never Too Early: Examining College-Going Culture and Access to a Local Private University for Elementary Latino Students
Presenter: Genesis Santos
PI: Dr. Kevin Magill
Latinos are underrepresented in higher education, but college-going cultures can help with postsecondary accessibility. The purpose of this study is to examine the college-going culture and the ways Latino students are supported in accessing a local private university at one elementary school in a Southwestern town. I utilized a community cultural wealth framework (Yosso, 2005) to understand how Latino students’ cultural capital is being used by the elementary school’s college-going culture. I conducted interviews with individuals connected to the school to analyze the college-going culture. Initial findings suggest that family and educator support and early college exposure exists, but the well-meaning messaging often lack explanation, context, and ground support. Implications suggest utilizing Latino cultural capital in college-going culture to increase college access among students, families, and institutions.
#2
Trait extroversion relates to cardiovascular reactivity but not habituation to repeated acute psychosocial stress
Presenter: Briana Roenz
PI: Dr. Annie Ginty
Research suggests the Big 5 personality trait Extraversion is associated with positive cardiovascular outcomes. Additionally, research has shown positive cardiovascular outcomes are linked to both cardiovascular reactivity and cardiovascular reactivity habituation in response to acute psychological stress. The present study aims to examine the association between extraversion and cardiovascular reactivity and habituation to acute psychological stress. Male and female participants (N= 467) completed two 4-minute mental arithmetic stressors, each with a separate baseline, during a single laboratory session. Heart rate and blood pressure were monitored throughout both tasks and participants self-reported their stress level immediately following each task. Extraversion was measured using the Big Five Inventory. High extraversion was significantly associated with cardiovascular reactivity. This was seen through lower systolic blood pressure reactivity (β = −.19, t = −3.96, p < .001), lower diastolic blood pressure reactivity (β = −.12, t = −2.54, p = .011) and lower heart rate reactivity (β = −.16, t = −3.46, p < .001) compared to people with low extraversion. High extraversion was also found to be associated with lower self-reported stress in the initial stress task (r(451) = -.12, p = .009). Extraversion was not significantly associated with cardiovascular reactivity habituation as seen through measurements of systolic blood pressure, diastolic blood pressure, and heart rate in the second task (all p’s >0.05). There was also no significant association (p > 0.05) between extraversion and self-reported stress during the second stress task. In this study, high extraversion was associated with initially lower psychological and cardiovascular responses to acute psychological stress. This finding suggests cardiovascular reactivity to stress is a psychophysiological mechanism linking extraversion to positive health outcomes.
#3
History of Intermittent Access to 20% EtOH On Behavioral Responses to Stress in C57BL/6J Male Mice
Presenter: Rika Morales
PI: Dr. Lara Hwa
Stress and alcohol drinking are naturally intertwined. In preclinical experiments exploring the role that alcohol plays on stress responses, male mice have been more commonly studied. There is an increase in alcohol use disorder (AUD) in women, so the need to identify sex-dependent factors in AUD has grown. The current experiments aim to compare female and male mice and their stress reactions after long-term alcohol drinking or no alcohol exposure. C57BL/6J male mice were given intermittent access to alcohol to two-bottle choice for 18 days to induce heavy voluntary drinking. After a 10-day period of protracted abstinence mice performed a series of behavioral tests which included the elevated plus maze (EPM), a predator odor stress test, and fear conditioning. After six weeks of drinking, it was found that male mice escalate their drinking when given intermittent access to alcohol. For the EPM, there were no significant differences in anxiety-like behavior between alcohol-drinking mice and H2O-drinking control group during protracted withdrawal. There were also no significant differences in avoidance behavior between groups for the predator odor stress test. However, alcohol drinking correlated with approach behavior to the predator odor, indicating abnormal stress responses. Additionally, while there were no significant differences between groups for freezing behavior in the shock-paired context and shock-paired auditory cue, there were differences in fear learning during the learning phase of fear conditioning. We can conclude that despite heavy alcohol drinking, at these time points, these stress tests might not be as sensitive to detect behavioral differences. We are looking to compare results between male and female mice to see if there are any sex-dependent factors. This research aims to explore prevention for permanent behavioral changes after long-term drinking to provide strategies and treatments for AUD.
#4
Racial Differences in Sleep Averages Over Time
Presenter: Leah Bullinger
Insufficient sleep can negatively impact individuals on social, academic, medical, and societal levels. Unfortunately, racial minority groups tend to be disproportionally affected by poor sleep and are more likely to face general sleep issues than non-minorities. However, there are gaps in the literature regarding the relationship between race groups and sleep averages over time. So, for this study, data was collected from five waves of The National Longitudinal Study of Adolescent to Adult Health (Add Health) to longitudinally assess racial differences in sleep (n = 2,427). One-Way ANOVA analysis showed that Whites tended to report the highest sleep averages, followed by Hispanics, participants in the “Other” race category, and Blacks. Furthermore, the data also showed that reported sleep averages decreased across all five study waves for the pooled sample (from 7.88 hours to 6.66 hours). These results suggest that the connections between sleep, race, and time are deserving of more investigation. Future research should aim to find effective solutions for racial disparities in sleep health and study further longitudinal trends.
#5
A Critically Appraised Topic: Intervention Outcomes for Children with Language Disorders and Challenging Behaviors
Presenter: Rhea Vikas
PI: Dr. Diane Loeb. First author: Rhea Vikas
Children with language delays or disorders often also display challenging internalizing and/or externalizing behaviours (i.e., hitting, yelling, anxiety, depression, etc.). A recent study indicated that speech-language pathologists struggle in knowing how to best provide services for children with challenging behaviors (Chow & Wallace, 2019). Because internalizing and externalizing behaviors are related to expressive and receptive language abilities (Bichay-Awadalla et al., 2019); targeting both with one intervention may result in better outcomes in less time (Armstrong, 2011). A Critically Appraised Topic (CAT) is one type of filtered data that involves a brief and rapid review of the current literature (White et al., 2017). In this study, a CAT was conducted to determine the outcome(s) of interventions that focused on both behavior and communication in children with comorbid behavior and communication difficulties. Six databases were searched and 262 articles were initially identified. Sixteen articles remained following review of titles and abstracts. Full-text reviews of the 16 articles applying inclusion and exclusion criteria resulted in four remaining articles. The four articles were then critically appraised and described in detail as the current best evidence available. Two of the studies were quasi-experimental designs and two were non-experimental studies (i.e., pre- and post-test design with no control). Three intervention approaches were effective for positive language and behavior outcomes and one intervention approach significantly improved behavior, but not communication. Theraplay, Parent-Child Interaction Therapy, and Applied Behavioral Analysis showed promise and yet require more rigorous study of their effectiveness that include control groups and randomization.
#6
Neuronal markers of escalated sucrose drinking in C57BL/6J mice
Presenter: Joyane Eriom
PI: Dr. Lara Hwa
Sugar, or sucrose, plays a large role in our daily consumption and healthy functioning. However, overconsumption of sugar can be problematic, so preclinical studies are necessary to monitor the behavioral progression towards diseases. Previous research has shown that intermittent exposure to sucrose using rats can produce sugar bingeing behavior. This study compares intermittent access to 4% sucrose to continuous access to sucrose to elevate consumption levels in C57Bl/6J mice. 24-hour sucrose preference and anxiety-like behavior will be measured after 12 intermittent or continuous days of drinking. During a final binge drinking day, brains will be collected for immunohistochemical c-Fos staining to measure neuronal activation in specific brain areas. Ongoing data suggest that mice given intermittent access to sucrose will escalate their voluntary sucrose drinking to higher levels than mice given continuous access. For brain site activation after a final sucrose binge, it is predicted that brain areas related to addiction and substance use, such as the prefrontal cortex, ventral tegmental area, amygdala, and dorsal raphe nucleus, may have higher c-Fos counts in the intermittent versus continuous access condition. Our studies suggest that binge-like sugar overconsumption can be modeled in mice by simply changing the schedule of availability. In addition to canonical brain sites involved in reward and the development of addiction, this experiment may reveal novel brain sites associated with sucrose binging. Ultimately, this research will have important implications for regulating junk food availability in vulnerable human populations.
#7
Magic Mushrooms: Treatment of Psilocybin, a Serotonin Agonist, for Treatment-Resistant Major Depressive Disorders Measuring Cerebral Blood Flow and Resting State Functional Connectivity with Magnetic Resonance Imaging.
Presenters: Joanne Kwak, Melody Golbarani
Psilocybin, a serotonin agonist and a classic psychedelic drug, occurs naturally in mushrooms and is structurally similar to the endogenous neurotransmitter serotonin. Psilocybin has an old history of medicinal use, but when administered in a supportive, careful environment, it can be used to treat emotional disorders. It has been shown to psychologically support a range of conditions like: anxiety, depression, alcohol and tobacco addiction, OCD, and treatment-resistant major depression. In this study, cerebral blood flow and resting state functional connectivity that is blood-oxygen level dependent is compared with functional magnetic resonance imaging (fMRI) to the before and after treatment with psilocybin for treatment-resistant major depression. In all patients, they were observed to have decreased depressive symptoms within a week and 47% met the criteria for response within 5 weeks. Brain analyses were done and showed decreases in post treatment in the cerebral blood flow. The decrease in amygdala cerebral blood flow is also related with the decrease in symptoms of depression. Increased resting state functional connectivity was observed within the post treatment. This research addresses the knowledge gap of the post-acute brain effects of psychedelics. It suggest that observed changes in brain activity are very different from high doses of psychedelic experiences than acute psychedelic states.
#8
The Effects of Copper Sulfate on the Regenerative Ability of Dugesia dorotocephala
Presenter: Adhwaitha Nambiar
PI: Dr. Marty Harvill
This study hypothesizes that any difference, whether low or high, in copper concentration will affect the regenerative ability in Dugesia dorotocephala. This preliminary study is designed to determine whether there is a correlation between copper levels and the regeneration of cut Dugesia dorotocephala, commonly known as Planarians. Three groups of experimental conditions were created based on differing copper levels in spring water: low, control, and high. Five planarians were placed in each of the four boxes for every experimental group and cut in half horizontally. Over the course of 16 days, the length of each cut planarian was measured and the ratio of alive to dead organisms was calculated. There was a positive correlation between copper concentration and regenerative ability in the control group. It was observed that the planarian survival rate was relatively low in the high concentration level group and that there was little movement in the low concentration group.
#9
The Effects of Aging on Medial Olivocochlear Neuron Morphology, Size, and Synapses
Presenter: Kimberli Taylor
PI: Dr. Dwayne Simmons
Though there is a known association between increased age and hearing loss, there has been little research done to understand the effects of aging on the auditory pathways of the brain. The superior olivary complex is located in the caudal pons of the brainstem, and functions as the first site where sounds from both the left and right cochleas converge to form a neural map of interpretable information. To investigate the effects of increased age in efferent signaling within the central auditory pathways, this study focuses on the structural change of the medial olivocochlear neurons in dTomato mice of different ages. More specifically, we are interested in differences in cell size, synaptic presence, and general morphology between these mice at 8 weeks and 43 weeks of age. We hypothesize that there will be a morphological change in efferent signaling neurons, which could be associated with age-related hearing loss.
#10
Identifying a Standard Pro-inflammatory Activator of Human Microglial Clone 3 Cells
Presenter: Bennett Schackmuth
PI: Dr. Erica Bruce
The human microglial Clone 3 (HMC3) cell line was initially established in 1995 and has since then been authenticated by the American Type Culture Collection (ATCC®). Since its establishment, HMC3 cells have been used in a multitude of studies to assess neuroinflammation and microglial activation. HMC3 cells are considered an optimal model of human embryonic microglial cells until a more cost-effective, simpler method can be developed to generate induced Microglial-like (iMGL) Cells from iPSCs. However, despite their widespread use and reported sensitivities to activation by various stimuli, such as lipopolysaccharide (LPS) and Phorbol 12-myristate 13-acetate (PMA), there is a large discrepancy on the reported effects of such stimuli on these cells. The goal of this study was to compare widely used chemical and biochemical pro-inflammatory activators to identify which one(s) can effectively induce activation of the M1 phenotype in HMC3 cells. HMC3 cells were briefly exposed to varying concentrations of LPS, IFN-y, and PMA. To ensure that pro-inflammatory responses were not transient, dosing schemes were run at both 24-hour and 4-hour exposure times. HMC3 cells were then stained for IL-6 and iNOS, two classic markers for pro-inflammatory phenotypes. Cells were then evaluated using the BD FACSVerseTM flow cytometer. Initial results show that at the 4-hour exposure mark, there was a significant increase in activation when stimulated with LPS, LPS+PMA, and IFNy+IL-1b. This study is significant as it identifies an effective M1 activator for HMC3 cells to be used as a control stimulus for proinflammatory phenotypes in further studies on neuroinflammation. Future experiments could be performed to assess similar phenotypic expression of the M2 anti-inflammatory phenotype under varying compounds.
#11
Detection and Quantification of smallRNA species in Bacteroides fragilis vs. Secretory Outer Membrane Vesicles: Effects on Colorectal Cancer Pathogenesis
Presenter: Michelle Pujol
PI: Dr. Joseph Taube
Colorectal cancer (CRC) is the third most common cancer worldwide and accounts for the second-highest number of cancer-related deaths. Moreover, patients with Inflammatory Bowel Disease (IBD) are at a significantly increased risk of developing CRC. The development of IBD and CRC are highly correlated with imbalanced intestinal microbiota composition. One such species, Bacteroides fragilis, can be present in the gut as either a commensal strain, nontoxigenic B. fragilis (NTBF), or as a pathogenic strain, enterotoxigenic B. fragilis (ETBF). Notably, recent studies have identified enterotoxigenic Bacteroides fragilis as a CRC candidate pathogen. Furthermore, gram-negative bacteria, including B. fragilis, secrete outer membrane vesicles (OMVs), which may pass through the mucosal layer to directly interact or fuse with human intestinal epithelial cells (IECs). These interactions between IECs and OMVs affect homeostasis and pro- or anti-inflammatory host immune responses. However, the microbial mechanisms that influence these responses represent a key gap in knowledge. It has been demonstrated that a major mode of communication between host and bacterial species are attributed to the extracellular smallRNAs (sRNA) encapsulated within OMVs, which can weaken or activate immune response. We aimed to investigate and compare the selective sRNA content of whole cell Bacteroides fragilis and their secretory OMVs using RTqPCR and gel electrophoresis for verification to understand the contribution of bacterial extracellular vesicles (OMVs) or their cargo sRNA species in microbe-host communication. Our results suggest that there is a selective process in smallRNA packing into outer membrane vesicles as evidenced by the dissimilarity of sRNA content of whole cell bacterial species and their secretory OMVs. This evidence suggests that these sRNA species could be governing microbe-host communication and furthermore, colorectal cancer pathogenesis.
#12
The Effects of Shock Therapy Before and During Regeneration in Dugesia dorotocephala
Presenters: Adley Kitchens, Lexi Haviland, Giulia Ishi
PI:Dr. Harvill
The purpose of this experiment is to measure the effects of shock therapy before and after regeneration in Dugesia dorotocephala. Dugesia dorotocephala serve as a model organism because of their ability to regenerate through the use of pluripotent stem cells. This process has been found to be affected through electric stimulus. Shock therapy is a successful mechanism used to help heal wounds in humans, by stimulating the production of growth factors, promoting healing. In this experiment, this data was applied to Dugesia dorotocephala to determine if electric shock would trigger the production of pluripotent stem cells in these organisms as well. Researchers hypothesized when the Dugesia dorotocephala are allowed to regenerate while undergoing electric shock, they will regenerate quicker, concluding that shock therapy heals wounds faster, allowing for a shorter regeneration period. Three groups were used; the first group was the control group, the second group regenerated while being shocked once a day, and the third group entered the experiment previously shocked for two weeks. After the Dugesia dorotocephala were cut, their length was recorded three times a week for three weeks to monitor the regeneration of their tails. The results did not support the original hypothesis. Visualization plots indicate Group 3 had the greatest increase in mean, while Group 2 does not show an overall increase. ANOVA test demonstrated that the results were statistically significant. In conducting this experiment, it will be beneficial to determine if shock therapy stimulates, delays, or inhibits growth by allowing the wound to heal.
#13
The role of the Nonsense-Mediated mRNA Decay pathway in S. cerevisiae response to low iron conditions
Presenters: Jana Chao
PI: Bessie Kebaara
Iron deficiency is a physiologically significant issue that has pathological implications in humans. Iron homeostasis is critical to all eukaryotic organisms because while iron is an essential micronutrient involved in crucial metabolic pathways, high levels of iron are toxic to the cell. The Nonsense-Mediated mRNA Decay (NMD) pathway, a highly conserved pathway present in the vast majority of eukaryotic organisms, regulates mRNAs by degrading mRNAs with premature termination codons and the expression of fully functional natural mRNAs. The NMD pathway has been shown to regulate mRNAs involved in iron homeostasis. When yeast cells experience iron deficiency, two transcription factors, Aft1 and Aft2, regulate the iron regulon which is a group of genes that are involved in the cell’s response to low iron conditions. Previous studies demonstrated the NMD pathway regulates some mRNAs in the iron regulon such as FRE2. Our research focus is to investigate whether the NMD pathway regulates the ARN family in low iron conditions in S. cerevisiae. The ARN family (ARN1-4) is a group of four iron-xenosiderophore-specific transporters belonging to the yeast iron regulon in the non-reductive iron import machinery. They transport iron across the plasma membrane. The open reading frames (ORF) of all family members were first amplified by PCR to be used as radioactive probes for detecting mRNA expression in low iron conditions using a wild type and NMD mutant S. cerevisiae strain. We found that ARN1 gene expression was NMD dependent and induced by low iron conditions. ARN1’s basal level expression seems to be kept in check by the NMD pathway. We will continue to probe the remaining ARN family members. Studying how iron homeostasis happens at the molecular level is indispensable to our evolving understanding of iron-related diseases.
#14
Components Towards a Mosquitocidal Plant
Presenter: Eric Jaramillo
PI: Dr. Christopher M. Kearney
Plant tissue culture using Impatiens walleriana and Impatiens balsamina is an effective way to introduce foreign genes to produce a transgenic plant. This could be done by using Agrobacterium tumefaciens strains that contain Green Fluorescent Protein using the 35S promoter from the Cauliflower mosaic virus. The tumor inducing plasmid in A. tumefaciens will work to help a binary vector introduce these foreign genes using transformation. Plant tissue transformed by the A. tumefaciens strains will fluoresce a green color under UV light. This transformed tissue will then be transferred to media that will let it produce shoots and eventually roots. So far, we have transformed three shoots that will be transferred to rooting media. From this a whole impatiens plant with the transgene will then be grown. Consequently, a model will then be available for a transgenic impatiens plant with an insecticidal peptide, called Hv1a, secreted from nectaries that will target and kill mosquitoes. This will aid in better living for humans and an effective defense against mosquito-borne diseases.
#15
Potential “Covert” Counter-defense Mechanism Found in Bacteriophage Albanese Gene 43
Presenter: Ignacio Rodriguez
PI: Dr. Tamarah Adair
The putative function of Gene 43 within arthrobacterphage Albanese has been annotated as a Cas4 family exonuclease; however, differences across databases indicate that this could be incorrect. Therefore, the purpose of this investigation was to determine whether gene 43 encodes for a Cas4 nuclease. Similarities between gene 43 and related nucleases (Cas4, AddAB, and RecBCD) were examined. Bioinformatics tools were utilized to generate a hypothetical gene 43 protein model for comparison with models of said nucleases. Close hits on NCBI-BLASTp, pointing towards Cas4, were all other phages with low similarity (26.6%). In contrast, the broader range of datasets, including non-phage genomes, on HHPred resulted in hits of greater significance (99.9%), belonging to an ‘AdnAB’ family protein, 6PPU. After comparing several hypothetical models generated via SWISS-MODEL, the 6PPR_B (variant of 6PPU) was selected for its greater statistical viability (0.44 QMEANDisCo Global out of maximum 0.50 and coverage of 0.77). A separate hypothetical protein template based on Cas4 was used as a template to prevent bias. FATCAT pairwise alignments provided three statistically significant matches to the gene 43 model: 6PPU_A with a chaining score of 535.25; 4ceh (AddAB) with a score of 371.30; and 4r5q (Cas4) with a score of 188.04. Alignment scores for the Cas4 template were all lower, but 6PPU was still favored over Cas4 (215.70 versus 200.91). These results suggest that Albanese gene 43 is most likely an AdnAB nuclease, due to the comparatively high chaining score and statistical significance.
#16
Assessing Pathogenicity of KCNH2 Variants in Cardiac Ion Channel Trafficking
Presenter: Luke Jones
PI: Dr. Brett Kroncke
Mutations in the KCNH2 gene are thought to be largely causative of long QT syndrome type 2. LQTS2 is a disease that affects the repolarization of the heart following contraction, and predisposes individuals to additional, potentially life-threatening, cardiac arrythmias. The precise classification of cardiac ion channel variants as pathogenic or benign is of significant importance in the clinical management of disease. Computational and experimental methods, in combination, are vital for generating accurate polygenic risk scores that use a numerical scale to predict the probability of disease manifestation. More specifically, predictive algorithms that can account for heterogeneous clinical presentations are of greater utility than mutational classification systems that fail to accurately account for and classify rare variants.
#17
Won't You Be My Neighbor?
Presenter: Lindsay North
PI: Jameson Graber
We construct a continuous mean field game model where like-minded individuals attempt to gather on a one-dimensional, ideological continuum. Intransigent players will minimize an individual total cost curve and are encouraged to cluster in densely packed, homogeneous neighborhoods. To observe the model’s behavior at Nash equilibrium, we discretize the initial and final population measures after an entire population is given the chance to shift to an optimized ideological position and establish a fixed-point algorithm to run numeric simulations on an array of initial population measures. Furthermore, we present iterated numeric simulations to suggest longer-term tendencies of dynamic mean-field game models.
#18
Nanoparticle Mediated HSC Delivery
Presenter: Chase Robinson
PI:Dr. Hans-Peter Kiem
Hematopoietic stem cells (HSCs) are progenitors responsible for creation of all blood cells in a process called hematopoiesis. Due to their capabilities for self-renewal and ability to widely differentiate, these cells can be used to treat a variety of blood cell diseases. With therapeutic applications from HIV to Sickle cell, the potential for genetically modified HSC treatment is great. However, current treatment methods like electroporation require ex-vivo modification. Expensive, wasteful for reagents, and geographically prohibitive, this method has measurable drawbacks. One proposed solution is the use of poly-beta-amino ester (PBAE) nanoparticles for in-vivo HSC delivery. My goal was to optimize the delivery of cargo to HSCs by experimentally varying both nanoparticle and concentration of mRNA. This experiment was an opportunity to learn nanoparticle formation, quality control, and the iterative approach to scientific inquiry. Nanoparticle mediated HSC delivery has promising therapeutic applications, particularly in protein or multiplexed editor delivery.
#19
Synthesis of Carbene-Borate Ligands for Catalytic Applications
Presenter: Ashley Farokhrouz
PI: Dr. Brian Lindley
Exploration of the reactivity between carbenes and anionic borate linkers has led to the development of new ligands with multiple strongly-donating carbene functionalities. These ligands have been previously used for a wide range of catalytic reactions. To expand on this promising class of ligands, we targeted borate-linked multicarbene ligands with different geometries than previously reported. Initial efforts to synthesize a ligand from diisopropylphenyl imidazole and a diphenylboryl linker were unsuccessful. The diphenylboryl linker makes characterization of product mixtures by nuclear magnetic resonance (NMR) spectroscopy difficult. To combat this, we set out to employ di(p-tolyl)boryl as a linker, with p-tolyl groups allowing for easier characterization of compounds via NMR spectroscopy. Specifically, we were able to synthesize di(p-tolyl) bromoborane via a new tin-free method using BBr3 as a reagent. Reaction of the di(p-tolyl)bromoborane with the diisopropylphenyl imidazole afforded us the desired imidazole-borane adduct. All compounds were characterized by NMR (1H, 11B, 13C), which confirmed the isolation of the target compounds. Future research of these compounds focuses on the deprotonation of the diisopropylphenyl-substituted imidazole-borane adduct with strong bases such as lithium hexamethyldisilazide (LiHMDS) to target carbene ligands. Continued research into the synthesis of these ligands will reveal their potential for future catalytic applications.
#20
Development of Boron-Based Ligands for First Row-Transition Metal Complexes
Presenter: Supriya Kotnani
Boron-based ligands have seen wide interest because of their utility in effecting stoichiometric and catalytic reactions in conjunction with transition metals. Our research group has recently developed new diborylamide ligands and demonstrated their ability to form strong bonds with alkali and transition metals. We sought to expand the scope of diborylaminde ligands, while simultaneously targeting a new class of borylated ligands derived from well-known pyridine imine ligands. For diborylamides, we successfully synthesized bis(trimethylsilyl)benzene and bis(dichloroboryl)benzene as ligand building blocks, which we treated with aryl and alkyl lithium reagents to observe their reactivity. Unfortunately, most attempts at synthesizing new diborylamides were unsuccessful, so we shifted our efforts towards the study of borylated pyridine imines. For the pyridine imine reactions, pyridine imines were synthesized via condensation of 2-acetylpyridine with either 2,6-diisopropylaniline or p-toluidine. Two pyridine compounds were successfully characterized by 1H nuclear magnetic resonance (NMR) spectroscopy. This marked a new synthetic route for the p-toluidine compound. Additional efforts to study these products’ borylation reactivity with boron tribromide are currently underway. These continued synthetic efforts show promise towards our initial goal to synthesize and analyze the reactivity of boron-based ligands
Pharmacokinetics of OXi8007 in a RENCA Mouse Model
Presenter: Caleb Tamminga
PI: Dr. Mary Lynn Trawick
Renal cell carcinoma (RCC) is one of the top 10 most common cancers in the world and most common type of kidney cancer. RCC is modeled in mice using the RENCA tumor model. RENCA is a murine kidney cancer cell line that can be orthotopically implanted into mouse kidney and is capable of spontaneous tumor formation in vivo. Tumors generated in the RENCA model and in RCC are characterized by extensive vasculature. Vascular disrupting agents (VDAs) are an emerging class of drugs designed to target the tumor vasculature and induce tumor necrosis. The Trawick laboratory is investigating pharmacokinetic response of a RENCA mouse model treated with OXi8007, a VDA prodrug of the parent antimitotic agent OXi8006 designed and synthesized by the Pinney Group (Baylor University). In this study, we are determining the concentration of prodrug OXi8007, active agent OXi8006, and associated metabolites in blood plasma, kidney tumors, and tissues from RENCA tumor-bearing mice at varying timepoints following drug administration (the Mason laboratory, University of Texas Southwestern Medical Center). The workflow for tissue analysis includes homogenization of a tissue sample in water using a Bead Mill, protein precipitation with acetonitrile, addition of an internal standard, centrifugation, and analysis of the supernatant by liquid chromatography/mass spectrometry (LC-MS) using a Thermo Orbitrap Q Exactive Focus. We have detected and quantified successful delivery of OXi8007 and its active form, OXi8006, to these kidney tumors, as well as other OXi8006 metabolites.