University Of Texas Rio Grande Valley

NIH Research Projects · FY 2026 · 2022-09

PROJECT SUMMARY/ABSTRACT Dental phobia is associated with avoidance of proper dental care, poor dental health, and decrements in social and oral quality of life. Although dental phobia may persist for many years, the disorder usually first manifests during childhood or adolescence. Hispanic youth may be at particularly high risk of developing dental phobia because Hispanic/Latino families are less likely to take a preventative stance toward dental health. This means that Hispanic youths’ first encounters with a dentist are more likely to be for treatment that is associated with pain, discomfort, or shame – the types of learning experiences related to the development of dental phobia. Although our knowledge about the etiology of dental phobia is well developed, we know considerably less about how to treat dental phobia in youth. Recently, a one-session exposure therapy treatment (OST) for specific phobias has proven successful in addressing a variety of phobias in children and adolescents. However, youth with dental/medical phobias have not been included in the trials assessing OST because of the need to include dental health professionals in the treatment. Therefore, the primary goal of this application is to prepare for and conduct a Stage III trial comparing OST for dental phobia in children and adolescents to an active control treatment in a predominantly Hispanic population and to examine inhibitory learning as the mechanism responsible for changes in anxiety and fear. The aims of the UG3 phase are to do the preparatory work needed for the trial, including the development of all study documentation and finalizing the clinical sites. Additional plans during the UG3 phase include the assessment of the acceptability and feasibility of the study procedures and a trial examining whether youth treated with OST show evidence of changes in inhibitory learning. The primary aim of the UH3 stage is to examine the efficacy of OST in a Stage III social/behavioral clinical trial in which OST is delivered by dental hygienists. This trial would randomize dental clinics to one of the two treatment arms (OST vs. Control) so that patient response and the hypothesized mechanism of treatment can be assessed. Factors related to future dissemination and implementation efforts will also be examined. It is hypothesized that OST can provide an efficacious treatment option that can be delivered by hygienists in the dental office. That is, that the treatment can decrease both anxiety and phobic avoidance in youth. Moreover, although exposure therapy has a high level of empirical support in youth and a good deal of laboratory work has been conducted to develop the theory to explains its effects, the main hypothesized mechanism of action – inhibitory learning – has not been studied as a mediator within the context of a clinical trial; therefore, this work could advance our understanding of the mechanism driving one of the most promising treatments for individuals with anxiety disorders.

NIH Research Projects · FY 2025 · 2022-09

Colorectal cancer (CRC) is the second deadliest cancer, and patients’ survival rate drops from 90% to 14% when cancer metastasizes to distant organs. Herein, we proposed investigating the role of a long noncoding RNA (LncRNA) in anoikis resistance and CRC metastasis. Metastasis is a multistep process, and one of the key steps is to acquire anoikis resistance to survive after detachment from the primary sites. Thus, understanding the molecular players involved in the anoikis process and metastasis could be vital for improving the survival of CRC patients. The aberrant expression of a long noncoding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been identified in CRC; however, its roles in metastasis processes are not yet well defined. Our preliminary results in the anchorage-independent growth (anoikis model) demonstrate increased lncRNA UCA1 and Glucose Transporter1 (GluT1) protein expression. Moreover, the overexpression of lncRNA UCA1 led to high Glut1 expression and higher glucose uptake in CRC cells, which indicates a potential mechanistic role of lncRNA UCA1 in anoikis resistance. In this study, we propose to elucidate the role(s) of UCA1 and its associated signaling pathways during anoikis resistance. We hypothesize that the overexpression of lncRNA UCA1 enhances CRC metastasis through anoikis resistance-associated signaling pathways. We will utilize Isogenic CRC cell lines SW480 (oncogenic) and SW620 (metastatic) to understand the mechanistic regulation of anoikis resistance. AIM 1 is proposed to elucidate lncRNA UCA1 associated molecular mechanisms involved in anoikis resistance and CRC metastasis. We propose to study the role of lncRNA UCA1 in anoikis resistance using Lentiviral transduced stable overexpression (SW480+UCA1//GFP) and knockdown (SW620+CRISPRgUCA1) cell lines using cell cycle, pro-survival, anti-apoptotic, stemness, glucose metabolism, kinase phosphorylation immunoprecipitation (IP), co-IP and Proximity Ligation Assay (PLA) assays. In AIM 2, we proposed investigating UCA1 linked proteins, RNAs, and pathways associated with anoikis resistance. We will use stable isogenic lncRNA UCA1 (OE and KD) cell line models and an unbiased approach to identify novel UCA1 associated/linked proteins and RNAs using Biotin-ReCLP (Reversible Cross-Linked Precipitation), in vivo RNA Antisense Proteomics (iRAP), and RNAseq analyses and validate them by RT-PCR, ddPCR, IP, co-IP and PLA studies. While AIM 3 is proposed to evaluate the functional impact of lncRNA UCA1 expression using a metastatic mouse model. In this aim, SCID adult male/female mice will be injected with Luciferase expressing validated stable isogenic human CRC cell lines (UCA1 OE and KD as in aim1) through the portal vein, and their metastatic potential will be evaluated by bioluminescence imaging. This study will provide new insights into CRC metastasis and will help in developing innovative therapeutics to improve patients’ survival, generate data for future NIH proposals, and training of students at the University of Texas Rio Grande Valley (UTRGV).

NIH Research Projects · FY 2026 · 2022-03

PROJECT SUMMARY/ABSTRACT Formation, maintenance, and/or modification of myelin is necessary for high order brain functions including learning, but it is still unclear whether myelin defects contribute to the onset of neurological conditions including Learning Disabilities (LD), Attention Deficit and Hyperactivity Disorder (ADHD), and Autism Spectrum Disorders (ASD). As genetic factors are believed to contribute to the onset of these conditions, the overall goal of this study is to define molecular links for defective myelin/myelination and subnormal learning and memory in a monogenic disease. Two myelin-centered mouse models of Costello Syndrome (CS) will be used as: CS is caused by mu- tations in a single gene (HRas); CS patients present with high predisposition to develop LD, ADHD, and ASD in correlation with abnormal myelin and White Matter (WM); and CS mouse models mimic diverse patient pheno- types. To test the hypothesis that a CS mutation impairs motor skill learning by disturbing the function and the timely/accurate formation of myelin, HRasG12V mutation will be induced in Oligodendrocytes (OLs; myelin pro- ducing cells) and OL Precursor Cells (OPCs) at strategic time points. Preliminary results support that HRasG12V in pre-existing OLs impairs learning of fine motor skills. Hence, Aim1 involves defining cell-autonomous/non-cell- autonomous mechanisms regulating this learning phenotype, particularly those linked to increased nitric oxide (NO) signaling. The Aim 2 will define changes in basal and learning-induced myelination, and functional connec- tivity upon HRas mutation in OPCs of the developing and adult brain. This study is original and innovative as it can impact our general understanding of brain function/dysfunction; it will be first in establishing developmental and chronic roles of HRas as the link for defective myelin and subnormal learning. Drugs studied used here - targeting glial NO - can diversify and expedite the development of treatments for CS and associated conditions. Finally, experimental evidence obtained will help settle the long-lasting debate on the links between abnormal myelin and the neuropathophysiology of RAS/MAPK pathway-related diseases (RASopathies). The PI’s expertise is in in vivo glial pathways and behavioral analyses and has been productive in RASopathy research. To establish a solid research program and become competitive for NIH R01 funding, training goals include attaining expertise in myelin biology, learning brain-wide research approaches (fcMRI, high-volume brain imaging), and acquiring a clinical perspective of RASopathies. Therefore, the mentoring team includes 1) a pio- neer scientist in myelin biology (~30 years in the field), 2) an expert/innovator in rodent MRI brain analyzes, 3) a leading clinician in RASopathies, and 4) a prosperous intramural scientist to guide the PI’s tenure promotion. The planned research and training were designed to promote the PI’s independence and to be foundation for an R01 application aimed toward defining myelin-regulated behaviors upon germline HRas mutation. Additionally, obtaining collaborations and preliminary data for electrophysiological analyses, behavioral tests of ADHD and ASD, and transcriptional and epigenomic analysis, among others, are scheduled in the period of support.

NIH Research Projects · FY 2025 · 2021-09

PROJECT SUMMARY/ABSTRACT A fundamental problem in cell biology is understanding how DNAs are structured by compaction in the densely packed cellular environment, and accurately passed down to daughter cells. Chromosome-associated proteins are key factors in dynamically and accurately organizing chromosomes, and directly influence the replication, transcription, and translation of genetic information. As such, many diseases including various cancers are linked to malfunctioning of chromosome-associated proteins. In a majority of bacteria, ParABS partitioning system and structural maintenance of chromosomes (SMC) protein complex are main contributors for chromosome segregation and organization. The ParABS system is composed of ATPase variant ParA, short palindromic DNA sequence parS, and parS-binding protein ParB. The parS sites are located in the vicinity of bacterial origin of replication. A longstanding conundrum in the chromosome biology field is that ParB proteins are not only found on the parS sites but also associate extensive (10-20 kb) flanking regions – a phenomenon termed spreading. It had been attributed to the ability of ParB protein to bridge different segments of DNA, that allows long-distance interactions. A new way of thinking derived from recent discoveries that ParB protein is not merely a DNA binding protein but also a novel CTPase enzyme. It was proposed that cytidine triphosphate (CTP) binding to the ParS and its subsequent hydrolysis cycle drives self-loading of ParS onto parS sites and subsequent sliding away from the loading sites. However, this “clamp and sliding” model alone has limitations in accounting for in vivo chromosome immunoprecipitation data. Another critical role of ParB proteins is that they recruit SMC protein complex to the vicinity of the replication origin. However, little has been known about the SMC protein recruitment mechanism. Once recruited, bacterial SMC is thought to organize DNAs by actively extruding DNA loops. This simple mechanism that can explain many aspects of chromosome structuring is required to be demonstrated with bacterial SMC complex. The PI has almost 15 years of single-molecule techniques expertise and his lab is devoted to elucidating the mechanisms of various DNA-binding proteins and their impacts on chromosome structure. During the next five years, the PI’s laboratory will tackle the outstanding problems of underlying ParB and bacterial SMC working mechanisms and their interplays utilizing his single-molecule approaches and newly acquired surface plasmon resonance (SPR)-based expertise. Information one could extract from those proteins in traditional biology approaches is possibly averaged out due to the nature of simultaneous measurements of multiple proteins (ensemble measurements). Our approach will be expected to uncover hidden mechanisms with unprecedented details. The in vitro results will be corroborated by in vivo-based assays and theoretical modeling. The proposed work will pave the way for other future DNA-protein interaction studies. The long-term goal of the PI’s research program is to elucidate how different DNA-binding proteins and their cofactors cooperate to maintain the genome stability and dynamics.

NIH Research Projects · FY 2025 · 2021-08

PROJECT SUMMARY/ABSTRACT Heart disease is the leading cause of death in the United States and together with cerebrovascular diseases account for over 28% of total deaths in the United States. Acute cardiac events (e.g., myocardial infarction, stress cardiomyopathy, and sudden cardiac death) are concerning because of their unpredictability and the lack of knowledge regarding causative mechanisms. Psychosocial stressors (e.g., anxiety, personality traits, social isolation) overburden the cardiovascular system and are risk factors for cardiovascular events and stroke. Characterization of heart-brain interactions in the context of psychosocial stress is an important first step in identifying gene-environment interactions that are associated with increased disease risk. Researchers have proposed that emotional and psychosocial stress may lead to a sympathetic-catecholaminergic surge that decreases myocyte viability and/or cardiac function. Hypothalamic arginine-vasopressin (AVP) and the V1A receptor (V1AR) have great therapeutic potential for psychosocial stress-associated heart disease, as AVP and its receptors promote health and survival by regulating neuroendocrine stress responses. The main thesis of this proposal is that AVP, acting via the V1AR, promotes health and wellbeing by dynamically modulating neural responses in the ventral tegmental area (VTA) to stressors. AVP is linked to stress-related disorders in humans and altered emotional reactivity in animals, that can be modulated by antipsychotic treatment, suggesting an AVP-VTA interaction in stress-associated responses. However, the neural mechanisms that underlie the relationships among AVP, Avpr1a gene expression, VTA-dependent stress responses, and cardiovascular function have not been fully characterized. To address this gap in knowledge, the major goals of this proposal are to investigate the cardioprotective properties of the neuropeptide AVP and determine whether there is an association between the Avpr1a gene expression, catecholamine release, and heart disease outcomes in a psychosocial stress-induced myocardial injury animal model. Many susceptible individuals are exposed to multiple risk factors that often interact with each other, magnifying cardiovascular disease risk. Using the Syrian hamster, I plan to investigate the interaction between two psychosocial risk factors, social isolation and aggression. Aim 1 will test the hypothesis that AVP in the VTA blocks stress-induced catecholamine release and exacerbation of myocardial ischemia-reperfusion injury, and aim 2 will test the hypothesis that V1AR gene expression patterns will predict response to stress and AVP- treatment on heart injury and catecholamines. The trainee will also participate in career development activities: learn how to perform myocardial ischemia-reperfusion injury surgeries and conduct gene expression studies; participate in a formal career development program; participate in a special program in cardiovascular genetics and epidemiology; complete scientific courses to gain new knowledge; improve grant writing skills by receiving mentorship from experienced investigators; and establish a successful independent research program.

NIH Research Projects · FY 2024 · 2020-09

Alzheimer’s disease (AD) affects a higher proportion of Hispanics - the fastest growing group of older adults in the U.S. - than Caucasians, and at younger ages. The causes of these differences are unknown, partly due to underrepresentation of Hispanics in AD research. Uncovering the reasons for this disparity may provide insight into the causes of AD and help to develop solutions and is this project's goal. Robust findings have linked the social and physical characteristics of neighborhoods to cognitive health, and the neighborhood - el barrio - is known to be important to Hispanic populations. However, identifying specific contextual and individual factors that affect risk of AD is a complex problem. This project aims to determine the effects of neighborhood factors on AD-like cognitive trajectories in Hispanic Americans, by a novel approach that integrates 1) individual differences revealed by high-dimensional multi-omics (genetic and metabolic molecular markers) and 2) mediation/moderation by family and neighborhood dynamics. Our access to a Mexican American cohort - the San Antonio Mexican American Family Study (SAFS) - will enable us to test if variations in AD-like cognitive trajectories across neighborhoods are explained exclusively by individual characteristics, or depend at least partly on social and physical elements of neighborhoods. SAFS participants have been deeply characterized for almost 30 years, including clinical (cardiometabolic and cognitive trajectories), structural neuroimaging, and environmental data; whole-genome sequencing (WGS), and other -omics (e.g., metabolic profiles, epigenomics, protein and RNA expression patterns). The specific aims of this project are to 1) determine if familism provides protection from AD-like cognitive decline compared to non-AD like cognitive decline in Mexican Americans; 2) analyze the associations between social and built environments of different neighborhoods and AD-like cognitive trajectories, by using online street imagery analysis of 17 neighborhoods within each of which at least 30 SAFS participants reside; 3) detect environmental (social and spatial) signals at neighborhood and family levels, reflected in any high-dimensional metabolomic/lipidomic, epigenomic, and transcriptomic biomarkers we find correlated with risk of AD-like cognitive decline; and 4) exploit the results to provide guidance for neighborhood-based projects aimed at decreasing the risk of AD-like cognitive decline, by developing a strategic communication toolkit, and convening a forum that will engage diverse stakeholders, particularly neighborhood designers and city planners. Overall, the results will elucidate pathways through which neighborhood-specific factors contribute to AD-like cognitive decline in Hispanics, offering new approaches to mitigation of AD.

NIH Research Projects · FY 2024 · 2020-08

PROJECT SUMMARY A diverse biomedical science research workforce is vital to the nation in remaining globally competitive in scientific discovery and innovation. One of the leaky pipelines in the pathway to research science careers is the matriculation of students at community college (CC) institutions and subsequently to baccalaureate programs at four-year institutions. Thus, this proposal aims to develop a program, which will support this pipeline between the University of Texas Rio Grande Valley and our partnering CCs, Texas Southmost College (TSC) and South Texas College (STC). These three institutions are in the Rio Grande Valley (RGV) of South Texas, which bears the disproportionate burden of health disparities such as obesity, diabetes and mental health issues which are exacerbated by poverty and illiteracy and are underserved in healthcare. These academic institutions are located in Cameron and Hidalgo County, which is characterized by a large Hispanic population (89.8 and 92.3%, respectively) and a high poverty rate (27.7 and 29.5%, respectively of the population living below the federal poverty line). Although UTRGV has memorandum of understanding with both TSC and STC to facilitate seamless transfer from the community colleges to, transfer rates to a BS degree program and specifically to the BS in Biomedical Sciences (BMED) at UTRGV are very low or vary between years. The impediments in transfer rates may be associated with a lack of awareness of the BMED degree program and career opportunities in biomedical sciences, specific academic preparation and adequate advising and support services for transfer and success in a 4-year college. Currently, we do not have a formal program that supports successful transfer from TSC or STC to UTRGV and successful completion of a BMED degree. In an effort to fulfill the long-term goal of the Bridges to Baccalaureate program to increase diversity in the biomedical research workforce, UTRGV, TSC and STC are committed to increase the number of underrepresented students who: 1) successfully complete their Associate degrees and transfer to the UTRGV BMED program, 2) complete the BMED program and 3) apply to graduate school and/or enter the biomedical science research workforce. Through self- assessment of areas that need to be improved and strengthened to achieve this goal, the following specific aims have been proposed: 1) Establish Partnership with community colleges to Recruit Potential Students who are Interested in Biomedical Sciences, 2) Develop Advanced Courses for Research Skills Development, 3) Provide Mentored-Research Experience Supplemented with Activities to Develop Research Competencies and 4) Develop Methods to Improve Biomedical Science Education.

NIH Research Projects · FY 2025 · 2020-07

Human Immunodeficiency Virus 1 (HIV-1) remains one of the leading causes of death worldwide predominantly in resource-limited countries. The present Combined Antiretroviral Therapy (cART) has significantly reduced disease mortality among patients. However, the virus still persists in viral reservoir organs such as Gut-associated lymphoid tissue (GALT). Mostly cART drugs have failed to eradicate GALT reservoir because of its complex physiology. In this regard, drugs that specifically reach out to that remote lymphatic tissue at therapeutic level for an extended period of time will be of current interest. Considering the next-generation therapy for HIV-1 as one of the priority research areas of Office of AIDS Research, we propose to develop a nanomedicine based long-acting anti-HIV drug formulation targeting Microfold cells (M-cell) in the GALT. M-cells are specialized epithelial cells that are predominantly present in the gastrointestinal tract. It effectively transports many micromolecules to the underlying mucosal immune system. Considering the transcytosis property of M-cell, we have developed a pluronic nanocarrier containing three currently recommended anti-HIV drugs (also called nanodrug). This nanodrug is bio-conjugated with anti-M-cell specific antibody for targeted drug delivery to M-cell. We hypothesize that an M- cell mediated drug delivery will be more sustained and effective than conventional drugs to the GALT.

NIH Research Projects · FY 2024 · 2018-09

Summary – Overall Alzheimer’s disease (AD) and AD-related dementias (ADRD) disproportionately impact Hispanic Americans, who exhibit AD/ADRD rates 1.5 times higher and average onset 7 years earlier than do older Whites. Predicted growth of the US Hispanic population, faster in Texas portends exacerbation of the elevated health and economic burdens of AD/ADRD in Hispanics. A shortage of researchers focused on AD/ADRD in Hispanic Americans, particularly from underrepresented racial/ethnic groups, restricts progress in this area, and is a key factor contributing to the severe underrepresentation of Hispanic Americans in research studies in AD/ADRD. To overcome these barriers, responding to NIA's AD/ADRD RCMAR Program (RFA-AG-23-025), and leveraging the robust mentorship and research infrastructure our RCMAR developed during the first 5-yr funding cycle, we aim to continue the Rio Grande Valley AD/ADRD RCMAR: Partnership for Progress at the University of Texas Rio Grande Valley (UTRGV), one of the nation's largest Hispanic-serving institutions. We will combine evidence-based mentoring and support mechanisms to develop and promote a first-rate regional and national cadre of researchers from underrepresented groups, to analyze the complex mechanisms and interacting factors that contribute to disparate Hispanic AD/ADRD vulnerability. The Center will support development of social and behavioral interventions using the NIH Stage Model for Behavioral Intervention Development, considering pathways and developmental time points at which changes in social circumstances and behavior can exert the largest favorable impacts on the prevention and progression of AD/ADRD among Hispanic populations. The Center will also exploit its unique resources to develop infrastructure and data collections that will attract and support researchers from multiple disciplines to conduct research aimed at reducing impacts of AD/ADRD on Hispanics. UTRGV's socio-demographic profile reflects that of its local community, positioning it uniquely to advance studies of disparities in health & health care and contribute innovative solutions to improve minorities' health. To achieve the Center's goals, the aims are: 1) Identify, engage, mentor, and provide high-quality training and individualized career development support to outstanding faculty, especially from underrepresented groups; 2) Support innovative, high-impact multidisciplinary pilot projects; 3) Continue providing expertise and resources for culturally-sensitive measures & analysis of cognitive risk factors in older Hispanics, including behavioral, neuropsychological, neuroimaging, cardiovascular, and genetic traits; and 4) Create needed expertise & resources to develop social/behavioral interventions at different ecological levels, via sustained community engagement of older Hispanics and their care partners in South TX. We will achieve these aims by continuation of 3 Cores (Leadership & Admin., Analysis, Community Liaison/Recruitment) and the Research Education Component. The Center will also leverage & build upon experience of collaborators at the UTRGV Institute of Neuroscience and the South TX Diabetes & Obesity Institute, and NIA-South Texas AD Research Center.