CTSI Translational Pilot Studies Program awards 13 new grants for 2022

Overcoming therapeutic resistance in prostate cancer remains a challenge in the clinic. In this study, investigators will use combined information of histopathology, transcriptomics, epigenomics, and proteomics with drug screens to determine what therapy would be most effective to a patient. Application of the tools provided from this study can be readily applied in the clinic to make more informed therapeutic decisions. This project has the potential to provide optimal therapeutic strategies for long-term benefit for patients with high-risk localized or advanced disease that no longer respond to standard of care.

Patients experiencing their first episode of a psychosis often gain substantial weight as a result of the medication they receive to control their disorder. This project will assess the feasibility and provide preliminary evidence of the efficacy of a program for first episode psychosis (FEP) patients that advances previous programs. Most FEP patients live with their parents, therefore, this project involves a parent in family-based treatment (FBT). In addition, dopamine antagonists used to treat FEP enhance the reinforcing value of food, and the proposed FBT will build alternative reinforcers to compete with food to reduce the impact of the medications on food reinforcement and the desire to eat.

This study aims to determine whether brain-derived neurotrophic factor (BDNF) and microRNA (miRNAs) can serve as novel biomarkers of recovery, and return of autonomic nervous system function after concussion. The project will expand upon previous work by examining the relationship between prescribed aerobic exercise and biomarkers in adolescents with sports-related concussion (SRC). The ultimate goal of this project is to develop a non-invasive, easy-to-use salivary test that enables clinicians to determine recovery from SRC and ultimately improve patient outcomes with prescribed aerobic exercise.

Catheter-associated urinary tract infection (CAUTI) is a major healthcare problem worldwide and extremely difficult to treat due to the presence of bacterial biofilms. Investigators have identified a need to develop novel, noninvasive approaches that can rapidly and completely eradicate catheter-associated biofilms. This proposal explores antimicrobial photodynamic therapy (aPDT) for the eradication of polymicrobial catheter biofilms. Based on preliminary data, researchers hypothesize that aPDT parameters can be optimized to eradicate catheter biofilms formed by a wide range of urinary microbes, and that aPDT represents an effective alternative to current treatment modalities.

Sepsis is a major contributor to morbidity and mortality in children. Delayed antimicrobial therapy increases the duration of organ dysfunction and mortality in pediatric sepsis, with rapid pathogen identification and appropriate antibiotic treatment being crucial to survival. Microbial culture remains the diagnostic gold standard for sepsis despite low sensitivity and specificity and delayed results. There is therefore an unmet need to develop rapid, point-of-care, diagnostic tools to identify pathogens and select appropriate narrow spectrum antibiotics for the treatment of pediatric sepsis. The goal of this pilot study is to test the feasibility of using metagenomic sequencing via the Nanopore platform for pathogen identification and prediction of antimicrobial resistance in critically-ill children with sepsis. This technology offers the possibility of fast pathogen detection and identification of antibiotic marker genes in an unbiased manner. Investigators will perform validation studies to determine the sensitivity, specificity, and applicability of this technique compared to Illumina sequencing and blood culture analysis for pathogen identification and profiling of antibiotic resistance.

The aging process is associated with loss of muscle mass and the majority of weight loss programs for older patients lead to further loss of muscle mass. Preliminary data indicate that semaglutide, a drug approved for treatment of obesity and type 2 diabetes, could target fat mass reduction while preserving muscle mass. Researchers will study the effect of semaglutide treatment on body weight and body composition in elderly obese subjects, and anticipate that semaglutide will induce significant weight loss in these patients while improving the overall proportion of lean body mass, potentially increasing muscle strength and mobility.

Oral cavity squamous cell carcinoma accounts for approximately 650,000 annual cases worldwide and efforts to improve survival and outcome have been hampered by increased recurrence rates, leading to a static survival rate. Tumors at anatomical subsites within the oral cavity have differing tendencies for recurrence/metastasis. While the underlying mechanisms are unclear, researchers hypothesize a role for the local microbiome. This study will determine whether there are microbiome signatures associated with specific tumor anatomic sites and disease progression and recurrence, and use this information to build a predictive model to help clinicians optimize treatment according to malignant potential.

Each year in the United States, one in 940 babies are born with cleft lip or palate, which is caused by disruption of palatogenesis during embryonic development. This project aims to delineate critical molecular mechanisms underlying cleft palate pathogenesis by using a newly generated laboratory mouse model to study how heparan sulfate modulates key signaling pathways during palatogenesis in the developing mouse embryo. This study is expected to advance our knowledge in palatogenesis and eventually lead to development of better methods for diagnosis, treatment, and prevention for cleft palate patients.

Studies have examined microbiome composition and diversity, and its relationship with disease, at selected human sites. However, few studies have evaluated the microbiome at multiple body sites in the same individual to understand the separate and potential synergistic effects multisite microbiota have on health and disease in aging. This pilot will provide critical data on feasibility, quality control, sample size, and power for an R01 grant to measure the microbiome at multiple body sites sampled in an ongoing study of older women, and evaluate microbiome associations (separate and synergistic) with aging-related diseases.

Bioinformatics analysis of GISAID epidemiology data shows reduced prevalence of virus Spike glycosylation mutations in the human disease population, suggesting that glycans are important for virus function. Investigators hypothesize that glycans play a major functional role in SARS-CoV-2 mediated infection and other coronavirus-related ailments. This study aims to help bridge the gap between studies performed with pseudovirus in BSL-2 setting and assays with the authentic SARS-CoV-2 virus in BSL3. Researchers hope to demonstrate that this can be used for a broad range of structure-function studies, and also in animal models.

With the introduction of long-acting injectables for pre-exposure prophylaxis (PrEP) to prevent HIV, clinical and translational research related to these new therapeutic agents is needed to maximize the benefits they offer through less frequent dosing schedules for the prevention of HIV transmission. This mixed methods project involves current healthcare providers, future healthcare providers (i.e., medical and pharmacy students), and patients currently taking oral PrEP. This pilot study aims to identify key barriers and facilitators in the PrEP care continuum and provide recommendations for intervention strategies that will accelerate adoption of long-acting injectable PrEP to reduce HIV infection among at-risk and underserved adult populations.

Individualization of a treatment regimen on a patient-by-patient basis using therapeutic drug monitoring is a critical part to treating bacterial infections in the hospital setting. Recent changes to the treatment guidelines for vancomycin have resulted in increased interest to using improved strategies that better account for patient-to-patient differences in achieving maximally precise dosing. Study investigators hypothesize that development of therapeutic drug monitoring that utilizes local Western New York epidemiology of resistant bacteria will provide highly precise PK/PD-driven drug regimens at the individual patient and bacteria level in Western New York.

Mindfulness-based intervention (MBI) is shown to reduce depression and anxiety across chronic health conditions, including pulmonary hypertension (PH). Underserved racial minority (URM) adults with chronic conditions such as PH can benefit from a mindfulness-based practice as a complementary health approach in symptom self-management and health promotion. Investigators hypothesize that a mindfulness mediation for adults with PH is acceptable to URM adults with PH, and reduces symptom burden, depression, and anxiety. This study aims to determine the feasibility, acceptability, and preliminary impacts of the mindfulness meditation for PH mobile-health program in URM adults with PH in symptom management and quality-of-life.