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Evaluating the Efficacy of CBP/p300 Inhibitors and Degraders As ADC/DAC Conjugates in Cancer Therapy
No full textCREB-binding protein (CBP) and p300 are essential transcriptional co-activators and histone acetyltransferases involved in oncogenic transcription across various cancers. Small-molecule inhibitors, such as IACS-16559, have shown therapeutic potential but are limited by hematotoxicity. This study evaluates the efficacy of CBP/p300 inhibitors and degraders-including IACS-16559, GNE-781, and JET-2091-in prostate cancer cell lines. We hypothesize that CBP/p300 degraders will exhibit superior efficacy compared to inhibitors, and we are also investigating PSMA antibody conjugation to enhance specificity and therapeutic potential. LNCaP and 22Rv1 prostate cancer cells were cultured in RPMI-1640 supplemented with 10% FBS and 1% penicillin-streptomycin, followed by treatment with serial dilutions of each compound over six days. Cell viability was assessed using Promega CellTiter-Glo reagent. Both cell lines demonstrated sensitivity to MMAE, aPSMA-MMAE (positive control), and JET-2091, with the degrader showing greater efficacy than inhibitors. Consistent trends were observed across both cell lines. A hook effect, indicating reduced binding efficiency at high concentrations, was noted with the degrader. These findings suggest that CBP/p300 degraders offer superior therapeutic effectiveness compared to inhibitors, supporting the initial hypothesis. The observed hook effect at higher doses underscores the importance of optimizing dosing strategies for future clinical applications. Keywords: CBP/p300 inhibitors, CBP/p300 degraders, PROTAC, PSMA, Antibody-Drug Conjugates (ADC), Degrader-Antibody Conjugates (DAC), cell viability, prostate cancer. [This project was completed with contributions from Gang Li from UT MD Anderson Cancer Center.]Honors Colleg
Role of Thioredoxin Interacting Protein in Nicotine-Induced Podocyte Injury
No full textCigarette smoking is a well-established risk factor responsible for a broad spectrum of diseases and is the leading cause of preventable deaths globally. Recently, we demonstrated that NADPH oxidase dependent O2•− production (ROS) mediates nicotine-induced NLRP3 inflammasome activation and thereby results in podocyte injury. However, it remains unknown how NADPH oxidase-derived ROS is sensed by NLRP3 inflammasomes in podocytes upon nicotine stimulation. The aim of this research project is to test whether thioredoxin-interacting protein (TXNIP) mediates nicotine-induced NLRP3 inflammasome activation and consequent podocyte injury. In vitro models using differentiated mice podocyte cells were employed to investigate the role of TXNIP in nicotine-induced NLRP3 inflammasome activation and podocyte injury. Cells were exposed to nicotine for 16 hours with or without TXNIP inhibitor (verapamil). Confocal Immunoflorescence analysis and Western Blot analysis were conducted to assess expression levels of active caspase-1 and podocyte-specific markers respectively. Immunoflorescence analysis showed that nicotine treatment increased active caspase-1 expression compared to the control. Furthermore, Western Blot analysis showed decreased podocin expression (podocyte damage) in the nicotine treated group as compared to the control cells. However, pre-treatment with verapamil, attenuated the nicotine-induced active caspase-1 expression and podocyte injury. Our observations reveal that TXNIP plays a pivotal role in nicotine-induced NLRP3 inflammasome activation and podocyte injury.Pharmacological and Pharmaceutical Sciences, Department ofHonors Colleg
Craving the Clouds: Approach Bias and the Struggle to Quit Combustible Cigarettes and Electronic Cigarettes
No full textDual combustible cigarettes (CC) and electronic (ECIG) users face similar health risks and prolonged nicotine addiction as exclusive CC smokers1,2. Addiction arises from imbalance between automatic/impulsive and reflective cognitive systems, fostering substance approach bias3,4 - an automatic tendency to approach rather than avoid appetitive cues.5 The Approach-Avoidance Task (AAT) is a validated tool to measure approach bias, yet no study has examined approach bias in dual CC/ECIG users.6,7 The current study seeks to examine relation between CC/ECIG approach bias and quitting-related processes. Approach bias (CC and ECIG) will significantly impact nicotine dependence, cravings, and quitting motivation, even after controlling for covariates (sex, age, income, cigarettes/day, ECIG puffs/day). [This project was completed with contributions from Mike Rinck from Radboud Universiteit and Jasper Smits from The University of Texas at Austin.]Psychology, Department ofHonors Colleg
The Effect of Social Comparison Feedback on Creative Performance and the Moderating Roles of Creative Self-Efficacy and Creative Personal Identity
No full textHow does social comparison feedback impact creative performance and do creative self-beliefs buffer or enhance the effects of feedback? We asked whether positive (v. negative) social comparison feedback influences subsequent creative performance, and whether creative self-beliefs, specifically creative-self efficacy or creative personal identity, moderates this association. Participants (N=201) were recruited from MTurk and responded to questions about their creative self-beliefs (i.e., creative self-efficacy and creative personal identity) and completed a creative performance task. Subsequently, they were given fake positive or negative social comparison feedback and completed another round of the creative performance task. After data collection, trained coders and two automated scoring methods were used to systematically evaluate participants’ creative performances. Data were analyzed using residualized change regression models. We found that creative personal identity buffered against negative feedback and protected future creative performance (β=0.20, p=.048). We replicated this finding using automated scoring of creative performance (β=0.34, p=.023). Moreover, we found that creative self-efficacy also buffered against negative feedback and protected future creativity when creative performance was assessed with automated scoring (β=0.15, p=.046). Results preliminarily suggest that people’s creativity was differentially impacted by social comparison feedback based on their creative self-beliefs
The Development of a Lunar Navigation System Utilizing Cost Based Path-Finding Algorithms
No full textAdvancements in spatial computing and spatial data science have provided crucial insight in terrain navigation. Innovations within these fields have laid the foundation for the creation of a global positioning system (GPS) that provides the most efficient path to one's intended destination. In terms of terrain navigation, the moon does not have as near of a robust system as the Earth does. Factors such as a hazardous terrain, the lack of landmarks and a lack of a GPS system are some challenges that arise with lunar navigation. The goal of my research was to implement a system that accounts for the moon's unique terrain.Computer Science, Department ofHonors Colleg
Construct as a First Step to Determining Ligand Preferences for Next-Gen Drug Design
No full textcGMP and cAMP play a key role in signal transduction, particularly in the rod and cone for vision, and in the olfactory bulb for smell, among other roles in humans. There are three A-type subunits that form functional channels when expressed alone and an A-type and two B-type subunits, which are only expressed alongside an A type. A functional channel is composed of four monomers each containing: i. A N-terminal region, ii. a transmembrane region which consists of six helical crossings and a pore region, iii. a C-terminal region which consists of a C-linker region, and a cyclic nucleotide binding domain. Previously, we constructed a soluble CNGA1 binding domain by replacing structurally similar binding domain of cyclic AMP receptor protein (CRP) with the CNGA1 binding domain (Scott, et. al. 2001). Using BL21(DE3) CRP- ChloramphenicolR competent cells, the CNGA3/CRP construct in the pet28a vector was expressed undergoing a 5-hour induction period at 25 degrees Celsius. This was followed by His-tag purification then size-exclusion chromatography. To recover protein from the inclusion bodies we underwent refolding experiments using guanidine hydrochloride and purified utilizing size-exclusion chromatography. Herein, we expressed and purified CNGA3/CRP binding domain construct and show that it binds 8-fluo-AMP which is replaceable by cAMP and cGMP. Our goal is to compare the ligand selectivity of the 10 human CNG and HCN channel binding domains, potentially informing future structure-guided drug design.Biology and Biochemistry, Department ofHonors Colleg
Self-Stigma Among Emerging Adults with Serious Mental Illness: Examining Developmental and Mental Health Outcomes
No full textThe impact of Self-Stigma on the developmental processes of Identity Exploration and Independence on the mental health outcomes of Depression, Self-Esteem, Why Try, and Quality of Life among emerging adults (ages 18-29) with serious mental illness (SMI) was examined. Hypotheses included that Identity Exploration and Independence would mediate the relationship between Self-Stigma and mental health outcomes. A sample of 239 emerging adults with SMI completed an online survey. Using observed variable SEM, results showed that the Harm stage of Self-Stigma (Harm) was associated with worse mental health outcomes including more Depression, more Why Try, and less Self-Esteem. Harm was not associated with Identity Exploration. Identity Exploration predicted higher Self-Esteem and less Why Try. Harm was associated with increased Independence, in the opposite direction than expected. Independence was related to higher Self-Esteem, higher Quality of Life, and unexpectedly, more Why Try. Two unanticipated minor positive indirect effects through Independence were found for Harm to Self-Esteem and for Harm to Why Try. A potential explanation for the unanticipated results is that Independence is achieved as a way to manage fears of ending up like a negative stereotype. Independence increases Self-Esteem and Quality of Life, offsetting Harm's negative impact. However, Why Try is elevated since Independence is rooted in Harm
Arbitrage Returns on the MISO Exchange
No full textThis paper examines arbitrage opportunities available in one of the largest wholesale electricity markets in the world, the Midcontinent Independent System Operator (MISO) electricity exchange. While prior research suggests that market efficiency on the exchange has increased over time, this study reveals that historical pricing information can still be used to generate positive returns. I find that a trading rule based on prior spot and forward prices generates statistically and economically significant risk-adjusted returns across the entire MISO footprint. These returns may in part be explained by the relatively small number of financial traders in the market and the ability of generation owners to exercise market power
Sleep and Academic Performance Among STEM vs Non-STEM Students at UH
No full textThis study explores the relationship between sleep habits and academic performance among STEM and non-STEM students at the University of Houston. The research investigates whether STEM students experience more sleep deprivation, lower sleep quality, and higher academic stress compared to non-STEM students. A survey with 59 participants that are UH students (ages 18-23) was conducted, collecting data on sleep quantity, quality, and its impact on academic performance. Results showed STEM students reported more sleep interference due to workload and stress while non-STEM students faced this issue to a lesser degree. Both groups slept between 6-8 hours, with STEM students generally getting less sleep. Sleep quality for both groups was mostly average or poor, though more STEM students reported poor sleep. Based on these findings. a health initiative was proposed using transtheoretical model to address sleep habits, focusing on awareness, resources, and behavior change. Further research should explore external factors like jobs, extracurricular activities, and pre-professional tracks that may influence sleep. The study concluded that workload, not major is a primary factor influencing sleep quality, and both groups face similar challenges. This highlights the need for broader support systems to address sleep deprivation among college students.Psychological, Health, and Learning Sciences, Department ofHonors Colleg
The Evaluation of Place of Service on the Treatment of Opioid Use Disorder
No full textPurpose: Delays in buprenorphine initiation remain a hindrance in therapeutic management of Opioid Use Disorder (OUD), with structural barriers to treatment and inequitable access to care, further complicating recovery efforts. We evaluate the impact of telehealth services on buprenorphine initiation among persons with OUD. Method: We utilized the Humana Integrated Medical and Pharmacy database to identify adult patients with confirmed OUD who initiated buprenorphine treatment between March 17,2020, and December 31,2023. Based on their index place of service, patients were categorized in-person or telehealth. Analyses included (i) Least Absolute Shrinkage and Selection Operator regression to identify predictors influencing treatment initiation via place of service; (ii) Inverse probability treatment-weighted (IPTW) multinomial logistic regression estimated the impact of place of service on buprenorphine adherence, utilizing group-based trajectory modeling: (iii) IPTW-Cox proportional hazard modeling assessed time to emergency department (ED) utilization between places of service. Results: Most patients initiated treatment in-person (81.5%), while 18.5% used telehealth. Younger adults (24-35: aOR: 1.55, 95% CI: 1.09-2.20), patients with private insurance (aOR: 1.98, 95% CI: 1.05-3.71), and patients in rural areas were more likely to initiate buprenorphine via telehealth. Patients with no comorbidities had increased odds of initiating via telehealth (aOR: 1.72, 95% CI: 1.31-2.26). A co-occurring diagnosis of cannabis use disorder (aOR: 1.42, 95% CI: 1.11-1.80), mood disorders (aOR: 1.23, 95% CI: 1.02-1.49), or sedative use disorder (aOR: 1.77, 95% CI: 1.34-2.33) raises the odds of telehealth initiation. Compared to patients in the adherent group, there was no significant difference in the likelihood of being in the rapid discontinuation group (aRRR: 1.02, 95% CI: 0.83-1.26) or the gradual decline groups (aRRR: 0.99, 95% CI: 0.76-1.29). We found no significant difference in ED utilization between groups (aHR: 0.98, 95% CI: 0.90-1.07). Conclusion: Telehealth-initiated buprenorphine yielded results comparable to in-person treatment in terms of medication adherence and ED use. However, sociodemographic and clinical variations indicate that telehealth might be a critical point of entry for certain groups. Limiting telehealth alternatives may prevent one in five patients from receiving care. Future treatment plans for OUD should consider the moderating impacts of geography, race, and mental health to provide individualized and equitable care