IMPRS 2019 works

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    Activation of the oncogene ERG by the Ras/ERK and PI3K/AKT pathways
    (2019-08) Willhite, Sydney; Strittmatter, Brady; Hollenhorst, Peter
    Background and Hypothesis: The TMPRSS2-ERG re-arrangement occurs in ~50% of prostate cancers and results in aberrant expression of the transcription factor ERG in the prostate. ERG is known to be activated by the Ras/ERK and PI3K/AKT pathways, however, the exact mechanism of this activation is not fully understood. The aim of this project is to identify how activation of these signaling pathways differentially effect transcription of ERG target genes. Experimental Design or Project Methods: In order to test how the Ras/ERK and PI3K/AKT pathways effect ERG target gene transcription, normal prostate epithelial cells (RWPE1) were transfected with constitutively active AKT in combination with phospho-mutants of ERG. These cell lines were then used to conduct Quantitative Reverse Transcription PCR and Western blotting of known downstream ERG target genes to identify how the activation status of these signaling pathways affected transcription and protein production. Results: Overall, our results demonstrate that ERG mediated transcription of the VIM gene, a marker of EMT, was activated by the Ras/ERK pathway and was repressed by the PI3K/AKT pathway. In addition, we found that ERG expression decreased FOXO1 protein expression in our cell lines regardless of Ras/ERK and PI3K/AKT status. Transcription and protein quantification was also measured for ERG target gene VEGFA, a critical regulator of angiogenesis. Conclusion and Potential Impact: This project helps identify the molecular mechanisms by which a common oncogene in prostate cancer is activated. Our results demonstrate how upstream signaling pathways differentially regulate oncogenic transcription and cell transformation. Overall, this project will provide insight to the molecular mechanisms of possible therapeutic targets in prostate cancer, the most common cancer amongst men.
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    Long-Acting Reversible Contraception (LARC) Knowledge and Intent to Use among IUPUI Students
    (2019-08) Asdell, Stephanie M.; Bennett, Rachel D.; Cordon, Sabrina A.; Zhao, Qiuhong; Peipert, Jeffrey F.
    BACKGROUND AND HYPOTHESIS: More than 50% of births to women in their early 20s are unintended, and unintended pregnancies have adverse consequences on students’ education. Long-acting reversible contraceptives (LARC), including hormonal and copper intrauterine devices (IUDs) and the contraceptive implant, offer highly-effective, long-term prevention of pregnancy, yet are utilized at low rates. Thus, we sought to assess students’ LARC knowledge and intent to use LARC at Indiana University-Purdue University in Indianapolis (IUPUI) to inform a campus family planning initiative. We hypothesized that students with higher levels of LARC knowledge are more likely to intend to use LARC in the future. We also hypothesized that a lower proportion of students utilize LARC compared to the US rate of 15.8% of all contraceptive users in 2017. EXPERIMENTAL DESIGN AND PROJECT METHODS: We designed a cross-sectional survey for undergraduates, graduate students, and resident physicians assessing sexual experiences, contraceptive use, LARC knowledge, and intent to use LARC. We summarized participants’ characteristics using descriptive statistics, compared awareness of LARC methods using McNemar’s test, and evaluated association between LARC knowledge and future intent to use a LARC method using Fisher exact. RESULTS: Thus far, we have recruited 126 participants with a response rate of 88.7%. Mean score on the 10-question LARC assessment was 5.2/10; higher levels of LARC knowledge were positively associated with future intent to use LARC (P < 0.05). Only 7.9% of contraceptive users surveyed used LARC, compared to 15.8% of US contraceptive users in 2017. Differences in awareness of the copper IUD (61.1%), hormonal IUD (74.6%) and implant (88.9%) were statistically significant (P < 0.05). The most common reason cited for not considering LARC use was “need for more information.” CONCLUSION AND POTENTIAL IMPACT: Low LARC knowledge and use and high desire for LARC education further supports need for a campus contraceptive initiative that will empower students to make informed reproductive decisions.
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    Predictors of Quality of Life after Liver Transplant
    (2020-11-14) Wu, Joey; Desai, Archita
    Background and Hypothesis: The impact of chronic liver diseases on patients and their family member is often understated and understudied. Chronic liver diseases can sometimes progress to a need for Liver transplant (LT). While recent studies have described quality of life (QOL) at different stages of liver disease, the impact of the patient’s QOL in LT survivors has not been examined. The importance of studying QOL in patients is due to its effect on the survivorship of LT recipients. We hypothesize that QOL in LT patients is lower than the general population. Our aim was to describe predictors of QOL in a well-described cohort of LT patients. Methods:Patients were enrolled at the Digestive and Liver Disease Liver clinic at Indiana University Hospital. All patients over the age of 18 were approached, if patients consented to the study, they were then enrolled during their liver follow up visit. The PROMIS survey was administered on an iPad and completed during the clinic visit. Survey were then scored and analyzed.Results: The T-scores for post liver transplant patients are lower in physical function, anxiety and depression, but higher in general life satisfaction compared to the general population. LT recipients have similar T-scores in Fatigue, Sleep disturbance, ability to participate in social activities, and pain interference compared to the general population. Conclusion and Potential Impact: Previous diagnosis of PBC, HCC, diagnosis of depression, household income, insurance status, Charlson Comorbid Index and number of non-transplant related medications have the highest association with quality of life. Further enrollment is needed to increase the power of the study. However, this can inform physicians the importance to taking these factors in to consideration in order to improve the QOL in LT recipients.