Project Title: Novel Therapeutic Approaches to Neurological Manifestations of Lysosomal Diseases

Faculty Mentor’s Name: Dr. Gustavo Maegawa
Phone: 352-294-5559

Research Project Description:

For the past years, my research laboratory has devoted to develop therapeutic strategies for lysosomal storage diseases (LSDs), inborn organelle diseases caused by mutation in genes encoding mostly enzymes that are essential for lysosomes to function as units of compartmental recycling and degradation. From a clinical standpoint, patients suffering from LSDs present involvement of multiple organs and systems, predominantly the central nervous system. Krabbe disease, also known as globoid-cell leukodystrophy, is a LSD caused by the deficiency of galactosylceramidase resulting in accumulation of galactosylceramide and psychosine, which is extremely cytotoxicto myelin-forming cells. Based on the above, there is interest in developing inhibitors of acid ceramidase to prevent psychosine accumulation. There is also interest in developing inhibitors of the enzyme that attaches galactose to ceramide (UGT8) analogous to what Genzyme has done for Gaucher disease. Such inhibitors may be useful for the treatment of GLD. The first step in this effort to develop new inhibitors is to develop new assays for these two enzymes that are appropriate for conducting high throughput screening of large compound collections (nearly 1 million compounds). Compounds discovered in this screen can be used in drug-development efforts to generate agents that are good enough to take into clinical trials for Krabbe disease. In the proposed studies we will develop high throughput assays of acid ceramidase and UGT8 that are appropriate for large-scale, high throughput screening of inhibitor leads. Aim 1: Prepare human UGT8 and develop a high throughput optical (fluorescence) assay for its enzymatic activity. Aim 2: Prepare human acid ceramidase and develop a high throughput optical (fluorescence) assay for its enzymatic activity. Aim 3: Test both assays in a screen of ~1,200 commercially available compounds. The outcome will be the identification of potential small molecule therapies to GLD, which can be used as model to treat neurological disorders affecting the myelin.

Entry Date: September 13, 2019

Project Title: Reliability of spot check transcutaneous hemoglobin measurements in children in the pediatric outpatient setting

Faculty Mentor’s Name: Dr. Molly Posa
Phone: (352) 222-9688

Research Project Description:

Currently the AAP recommends universal screening for IDA at the 12-month-old well child visit and at any age in children who are at increased risk for iron deficiency. The current method for testing for iron-deficiency anemia is through a finger stick to collect a capillary blood sample. Given this is an invasive procedure, this frequently causes stress to both the child and the parent because of the discomfort causes to the child. There is a noninvasive transcutaneous hemoglobin test available, but little research has been done to determine the reliability in the outpatient pediatric setting. Our study assessed the accuracy and reliability of a non-invasive hemoglobin measurement device compared with our standard capillary measurement in an outpatient pediatric office.

Enrollment included any pediatric patient who needed a hemoglobin measurement from July 2019 through April 2020. Each child had a hemoglobin measurement obtained with Pronto Pulse Co-Oximeter followed by capillary sample that was obtained and resulted in clinic. Paired hemoglobin results will be compared.

The medical student will be responsible for completing a retrospective chart review of pediatric subjects to collect data including: capillary hemoglobin value, transcutaneous hemoglobin value, age, weight, race, perfusion index, sick vs well clinic visit and if any other blood tests were obtained during the visit. The correlation between the two measurements (capillary vs transcutaneous) will be evaluated on Bland-Altman analysis. Data collection is currently ongoing, but expected to be completed in April 2020 in order to start working on analysis analysis in May/June 2020. Medical students will participate in data collection and analysis of the chart review along with preparation of abstracts and manuscripts resulting from the study. Results of this study will help determine the validity and reliability of a non-invasive hemoglobin measurement device in the outpatient pediatric clinic setting.

Entry Date: September 30, 2019

Project Title: UF Healthy Kids Medical-Legal Partnership

Faculty Mentor’s Name: Dr. Rachel Coleman
Phone: 508-523-9361

Research Project Description:

Our Healthy Kids MLP is helping our Pediatrics department address the gaps in care for our most vulnerable patients, improving patient access and quality of care in a number of different ways. Current research estimates that approximately 60% of a patient’s health is determined by social factors where they live, work, learn, and play. I serve as the Medical Director for our Pediatric Medical-Legal Partnership (MLP). Through our MLP, we are working to address these social factors impacting patient health and provide a more complete medical home. Currently, we are screening patients in our Severe Asthma clinic for Health Harming legal needs. In the near future, we plan to begin screening patients in our Pediatric Diabetes clinics as well as our Pediatric Sickle cell clinics. Next summer, we would like a student to help with an evaluation of our MLP in a few ways. We would like to compare the patients screened in each clinic to discover how they are similar and different. In addition, we would like to analyze the types of legal needs that are being identified and how we might better serve the patients in those clinics as a whole by additional services.
Additionally, we hope to survey our pediatrics residents, faculty, and staff to determine their knowledge base about SDOH (social determinants of health), HHLN (health harming legal needs), and/or community resources before and after interventions to help with planning future curriculum. The student who takes this position would also be a part of the Department of Pediatrics Health Outcomes Summer Lecture Series which would give them vital additional training on their research project.

Entry Date: November 7, 2019

Project Title:Management and Outcomes of Cerebral Vasculopathy in Children with Sickle Cell Disease: a Retrospective Registry

Faculty Mentor’s Name:Dr. Philipp Aldana

Research Project Description:

Children with sickle cell disease (SCD) are at significant risk for stroke despite best medical management. Cerebral revascularization surgery (CRS) is effective in other diseases in the prevention of stroke due to cerebral vasculopathy, such as Moyamoya syndrome (MMS) – one of the types of vasculopathy seen in SCD. While preliminary studies have shown that these interventions can possibly reduce the risk of stroke in pediatric SCD, they have been mainly single-center case series with small sample sizes. The patients identified to be at high risk for stroke have been managed via existing protocols to diagnose them with cerebral vasculopathy and referred for neurosurgical evaluation when appropriate. Following neurosurgical evaluation, surgical intervention may be recommended to the appropriate patient. These interventions can include CRS procedures as well as obliteration of cerebral aneurysms. However, the role of CRS in this patient population is not clearly defined. Thus, this study aims to compare the stroke outcomes in pediatric patients with SCD and MMS following best medical management alone to those additionally undergoing CRS.

As a multi-center, retrospective cohort study, the objective is to determine the role of CRS in this patient population by examining the surgical indications, techniques, outcomes and adverse events of the procedure. Patient characteristics and stroke occurrence will be compared between those who underwent CRS and those who underwent conservative treatment. Medical students would have the opportunity to analyze data, assist with data accuracy of research data between institutions, and help draft the manuscript.

Entry Date: November 26, 2019

Project Title:Targeting Primary Central Nervous System Lymphomas

Faculty Mentor’s Name:Dr. Paul Castillo

Research Project Description:

Primary central nervous system lymphoma (PCNSL) is mainly caused by a diffuse large B‐cell lymphoma (DLCBL) that accounts for 2% of all brain tumors. Despite standard of care treatments, PCNSL is considered an aggressive neoplasm with most patients dying within 2 years from initial diagnosis. The blood–brain barrier permeability is a major limitation for current treatments, hence innovative approaches to bypass this obstacle become an attractive unmet need.

Our lab has extensive experience using immunotherapy with promising results treating brain tumors. We propose innovative types of intracranial delivery of nanoparticle vaccines to enhance the native and adaptive immune system against unique and exclusive tumor antigens derived from PCNSL murine models.

The student would be able to learn the workflow of a translational lab and techniques such as nanoparticle manufacturing, sterile techniques in tissue culture, RNA extraction, electroporation, PCR, ELISA, and small rodent handling to perform in vivo experiments.

Entry Date: November 23, 2019

Project Title:Longitudinal Musculoskeletal Ultrasound Assessment in Juvenile Idiopathic Arthritis

Faculty Mentor’s Name:Dr. Leandra Woolnough

Research Project Description:

The purpose of this study is to determine the prevalence of ultrasonographic inflammatory changes in the joints of patients with Juvenile Idiopathic Arthritis (JIA) in comparison to healthy children. A secondary aim of this pilot study is to determine if inflammatory joint changes in patients with JIA detected by ultrasound (US) can augment the clinical musculoskeletal assessment in establishing disease severity and predicting disease progression. The overall goal of this study is to further delineate the role of ultrasound in the diagnosis and management of patients with JIA. We aim to improve understanding of the use of US for diagnosis as well as monitoring disease and therapy response in JIA patients.
This work is funded by the Childhood Arthritis and Rheumatology Research Alliance (CARRA).This project is approved by the IRB.
The student will assist in patient recruitment, administering surveys to patients in clinic, and data compilation. They will also get a unique opportunity to learn about using ultrasound to evaluate joints in kids. The student will be invited to participate in the summer research series within the Health Outcomes and Policy track to learn poster and presentation skills.

Entry Date: November 26, 2019

Project Title:Improving glycemic control among children and adolescents with obeistya nd prediabetes with real-time feedback via continuous glucose monitoring and virtual medical nutrition therapy

Faculty Mentor’s Name:Dr. Angelina Bernier

Research Project Description:

The goal of this project is to see if real-time feedback via continuous glucose monitoring (CGM) and virtual medical nutrition therapy can improve glycemic control in children and adolescents with obesity and prediabetes.
We will be applying current diabetes glucose monitoring technology to a new population of patients to have prediabetes which is a risk factor for development of type 2 diabetes. Our intent is to determine whether post prandial glucose biofeedback will change eating behaviors in children with obesity and risk for diabetes. We will be applying this technology with instruction and guidance from medical nutrition therapy (MNT) with a focus on reducing foods with high glycemic index by a register dietitian nutritionist (RDN) in the IFAS extension system.
The initial aim of the study will be to develop a virtual MNT program for patients and caregivers to be delivered by extension agents who are also licensed RDNs over the first few months. The second aim is to evaluate the impact of a CGM sensor and virtual MNT on biochemical markers of prediabetes and dietary intake. Students in this study will have the opportunity to work on literature reviews of optimal MNT in prediabetes in response to glucose excursion data; recruit patients from our metabolic clinics; wear and learn to train patients on placement and use of these devices; and finally track data using a REDCAP registry.

Entry Date: December 4, 2019

Project Title: Determining iron overload in pediatric cancer survivors

Faculty Mentor’s Name: Dr. Tung Wynn
Phone: (352) 273-9120

Project Description:

Pediatric cancer survivors are an increasing population. Blood transfusions are commonly given as a part of most pediatric cancer treatments and contribute to iron overload. The prevalence of the genes associated with hereditary hemochromatosis (HFE) and polymorphisms of these genes are generally common. Often these are associated with abnormal iron studies, even if a clinical diagnosis of hemochromatosis or iron overload can be made. It is also reported that people with HFE mutation and polymorphism have increased rates of cancer development. This project seeks to review the registry of Long term Pediatric Cancer survivors at UF and determine the rates of hemochromatosis and the rates of HFE gene mutations and polymorphisms in this population.

Entry Date: December 20, 2019

Project Title: Pediatric HIV Database

Faculty Mentor’s Name: Dr. Frances Saccoccio
Phone: (352) 294-8591

Project Description:

Quality improvement project to develop 2 RedCap databases that will be used to improve the complex care of pediatric patients living with HIV or perinatally exposed to HIV.
1. Pediatric patients living with HIV – This database will provide a searchable means to determine our patient’s last visit and to identify patients at risk for complications. This project includes creation of the database and entry of data from previous visits. Once this database is complete it will be used to identify patients without viral suppression and at risk for complications of antiretroviral medications such as obesity and decreased renal function.
2. Infants with perinatal HIV exposure – This database will provide a searchable means to determine our patient’s last visit and if testing is up-to-date per guidelines. This project includes creation of the database and entry of data from previous visits of infants currently being following by our practice with perinatal HIV exposure.

Entry Date: April 17, 2020