Research has shown that drinking motives (or reasons for consuming alcohol) are strong predictors of alcohol use; moreover, enhancement and social motives are among the strongest predictors of alcohol use. Given limited research to date, the purpose of the current study is to examine how drinking motives relate to drinking alone and also to drinking with friends. College student drinkers ages 18-24 were recruited for an ongoing study. To be eligible, participants had to report alcohol use two or more days a week and one or more occasions of heavy episodic drinking in the last two weeks. Baseline data on alcohol use, drinking motives, and drinking context were used for the current analyses (N = 292 to date; 52% female, 71% Caucasian, mean age = 20.17 years). Participants were asked to report how often they drank alone and with friends on a scale from “never” to “daily or almost daily.” In addition, they were asked to report motives for drinking on each of five subscales using response options from “almost never/never” to “almost always/always." The current study will use regression analyses to test associations with four of the subscales: coping-anxiety, coping-depression, enhancement, and social motives. We hypothesize that higher coping motives will be associated with being more likely to report drinking alone and with friends. Additionally, we hypothesize that higher social and enhancement motives will be associated with being less likely to report drinking alone and more likely to report drinking with friends. Results from this study will provide a better understanding of why people decide to drink and in which different social contexts, thus providing valuable information to guide interventions on how to better incorporate drinking motives and social context.

With advances in sequencing technology it has become feasible to sequence a patient’s genome in a clinical setting, but our ability to interpret the effect of genetic variants on health and disease remains a large challenge. Genome-wide association studies (GWAS) have helped to interpret DNA variants by correlating thousands of variants in the genome with disease. However, many of these variants fall in noncoding DNA (making it hard to predict their effects) and are often in tight linkage with neighboring single nucleotide polymorphisms (SNPs) (meaning these neighboring SNPs may also be responsible for driving the correlation with disease). Consequently, most disease-associated variants still need functional validation. There is mounting evidence that a large number of these variants may be effecting gene regulation (when, where, and to what degree a gene is expressed), and several groups have tried testing whether these SNPs effect regulatory activity with traditional reporter assays. In this study, we aimed to validate GWAS candidates linked to osteoarthritis, a joint disorder with several SNPs previously associated. We compiled a list of these variants as well as all SNPs in linkage disequilibrium, for a total of 1,605 variants. To screen this list for functional candidates, we leveraged “self-transcribing active regulatory region sequencing” (STARR-seq), a reporter assay that can test thousands of sequences for regulatory activity in a single experiment. Our screen identified two variants with statistically significant differences between the major and minor alleles. To validate these findings in the genome, we introduced the minor allele of one variant into cell lines via CRISPR/Cas9. We found a similar difference in transcription between the major and minor allele in the genome as our initial episomal screen. We are currently working with our collaborators to further validate these findings in patient samples.

Research has examined the association between marijuana use and delay discounting (i.e., relative preference for immediate versus future rewards). However, limited research has compared those who use marijuana and those who do not on future self-consideration. The purpose of this study is to examine the association between marijuana use and consideration of consequences. College students ages 18-24 were recruited for an ongoing study. To be eligible, participants had to report alcohol use two or more days a week and one or more occasions of heavy episodic drinking in the last two weeks. Baseline data were used for the current analyses (N = 292 to date; 52% female, 71% Caucasian, mean age = 20.17 years). Participants were asked to report on current marijuana use, number of hours high from marijuana in a typical week, and number of marijuana-related consequences experienced in the last three months. To assess participants’ consideration of immediate rewards and future consequences, participants answered questions on the Zimbardo Time Perspective Inventory (ZTPI) and the Consideration of Future Consequences (CFC) scales, respectively. Independent samples t-tests will compare current marijuana users (57%) to nonusers (43%) on CFC and ZTPI scores. We hypothesize that students who report current marijuana use will report significantly lower scores on the CFC scale (i.e., less consideration of future consequences) and significantly higher scores on the present hedonistic ZTPI subscale (i.e., greater consideration of immediate rewards) compared to those who do not use marijuana. Among marijuana users, regression analyses will examine associations between the CFC and ZTPI with levels of marijuana use and consequences. We hypothesize that people who score lower on the CFC and higher on the ZTPI will report higher marijuana use in a typical week and more marijuana-related consequence. Results will inform how future-self consideration may be addressed in interventions.

The development of neurodegenerative diseases, such as Parkinson’s, Huntington’s, and Alzheimer’s affect millions of people every year. Previous studies have shown that an enzyme found in the endemic Herpes Simplex Virus (HSV-1); UL12.5, degrades the mitochondrial genome, which we hypothesize may predispose patients to neurodegenerative conditions. A majority of the human population is infected with HSV-1 and other herpesviridae, which encode similar enzymes, and their reactivation is commonly seen throughout life. We have found that the degradation of mitochondrial DNA by UL12.5 activity is widely conserved and when UL12.5 is expressed in the model organism, Caenorhabditis elegans (C.elegans), mitochondrial DNA content drops nearly 10-fold. Interestingly, we find that activation of the HSV-1 UL12.5 enzyme alters cellular proteostasis; the cell’s mechanism for maintaining properly folded and functional proteins. This change in proteostasis alters the aggregation of misfolded proteins, especially those involved in the cause of neurodegenerative diseases, and leads to neurological phenotypes like paralysis, which we can quantify in the worm. To study the enzymatic activity of the UL12.5, we used modified worms expressing the protein using an inducible transgene that can be verified by fluorescent microscopy. The effects of the UL12.5 activity is determined by tracking lifespan of worms, performing paralysis assays, and counting protein aggregates with controls that use a catalytically inactive version of UL12.5. We have also found that Emodin, a compound found in traditional Chinese medicine, which has previously been shown to inhibit UL12.5, alters the activity of UL12.5 in a worm model of Huntington’s disease. We hypothesize that activation of this enzyme may cause similar pathologies in the human brain and may be a causative factor in human neurodegenerative disease. Further, inhibitors of UL12.5 like Emodin may prove useful therapeutics for treating neurodegenerative diseases.

2-deoxy-ATP (dATP) is a nucleotide used in DNA synthesis and its presence has been seen to improve the magnitude and rate of contractions in heart muscle cells. However, levels of dATP are naturally low in mature cells. As an attempt to develop a novel treatment for heart failure, methods to increase the expression of ribonucleotide reductase (RNR), a key enzyme in the production of dATP are being investigated. RNR is regulated by ubiquitin-proteasome degradation of the Rrm2 subunit. We constructed a variant version in which two regions were changed to prevent ubiquitination. This new variant should lead to higher levels of RNR in cardiomyocytes, which also indirectly increases levels of dATP. Our preliminary results show a successful increase in levels of both RNR protein and dATP in cultured neonatal rat cardiomyocytes. Although levels of RNR and dATP were increased, the level present in our cultured samples are much higher than expected for adult rat and mice cells. Therefore, we are currently testing this RNR variant in vitro in cultured adult rat cells, as well as in vivo in aged adult mice. These models are more representative of a therapeutic use. Preliminary results have been promising toward identifying a more effective method of increasing dATP levels for improving cardiac function.

The Digital Future Lab is creating a 3D strategy game called “SEED”. It is a reverse tower defense game in the sense that rather than set up obstacles (towers) on a playing field to stop or destroy waves of enemies from reaching their destination, you set up towers, in this case helpful characters called Muses, to help waves of creatures called Tali along their hazardous journey across the playing field. My responsibilities for SEED were making assets and creating concept art to help in the 3D pipeline. Using Adobe Photoshop, I painted concept art that refines the 2D designs of other students to prepare them for modeling and texturing in a 3D space. It is difficult to imagine certain design or visual ideas without a visual representation and so I created diagrams and sketches to aid my team members. In order for a character to work in a 3D space, certain aspects of its design needed to be altered in order for it to be easily animated, as well as for it to look good in the game itself. In addition to designing these characters, I modeled them using Autodesk Maya and textured them using Substance Painter. As of now, these characters have been fully modeled and are in the game. Apart from that, I also determined the look and feel of the environment of the game and created concept art in order to unify the visual experience between all these different, complex elements. Ideally, all this work will go towards immersing and wowing a player when they first load into the game.