2016 CTRI Pilot Project Recipients

Clinical Research | Translational Research | Innovative Technology | Academic-Community | Dissemination and Implementation Research

The CTRI announces the selection of the 2016 Pilot Projects. Fourteen projects were chosen in five categories, including Clinical Research, Translational Research, Innovative Technology, Academic-Community Partnership, and Dissemination and Implementation. Pilot Project grants are one-year competitive cash awards for researchers to obtain preliminary data. Funding priority is given to junior faculty members. Below are the 2016 projects.

Funding Period is April 1, 2016 (upon IRB Approval) through March 31, 2017.

Clinical Research Pilot Projects

Paula Aristizabal, MD, MAS Paula Aristizabal, MD, MAS
UC San Diego Department of Pediatrics/Rady Children’s Hospital
Department contributed to pilot project funding

Title: Factors affecting Parental Satisfaction, Anxiety and Comprehension of the Informed Consent in Pediatric Oncology Clinical Trials

Pediatric cancer survival rates have improved dramatically, in part due to high patient enrollment in clinical trials. Hispanic children have higher incidences of certain cancers than Non-Hispanic Whites, but poorer survival rates. Postulated reasons for these worse outcomes include the lower participation of Hispanics in clinical trials, despite the National Cancer Institute’s efforts to improve clinical trial recruitment in minorities. Current informed consent standards are aimed at promoting equality when conducting research across diverse populations. However, Hispanics and those with limited English proficiency may face increased barriers during the informed consent process. Low participation of racial/ethnic minorities in clinical trials may result from the complexity of the informed consent.

This project will examine the influence of race/ethnicity, language, socio-economic status (SES), health literacy and acculturation in the informed consent process in pediatric oncology, with particular focus on Hispanics. Our primary aim is to examine factors affecting parental comprehension of the basic concepts of the informed consent for pediatric clinical trials. Secondary aims include exploring the effects of parental level of satisfaction, perception of voluntariness, anxiety and decisional regret on the informed consent process.

Findings derived from this study will constitute an initial step to understand differences in the informed consent process in relation to Hispanic ethnicity, language, SES, health literacy, and acculturation. This is an essential first step towards designing targeted interventions to improve the informed consent process for pediatric oncology clinical trials in underserved populations, particularly Hispanics, the fastest growing racial/ethnic group in the U.S.

Edward Chao, DO, MA Edward Chao, DO, MA
UC San Diego Department of Medicine
Department contributed to pilot project funding

Title: Studying the Effectiveness of Non-Invasive Glucose Sensors in Patients with Diabetes:  The SENSOR Study

Self-monitoring of blood glucose (SMBG) can both facilitate and hinder adherence in patients with diabetes mellitus. Readings provide real-time information on hypoglycemic and hyperglycemic excursions. These data are crucial to successfully managing this disease, as SMBG can help guide decisions on titrating medications, and can potentially encourage patient engagement. There are drawbacks. Piercing the skin to check glucose up to several times a day can be uncomfortable and obtrusive for a patient with diabetes mellitus. SMBG offers only a snapshot of the patient’s glucose at the time of testing.

Continuous glucose monitoring (CGM) can reveal glucose trends. A subcutaneous sensor transmits interstitial glucose readings approximately every five minutes. Yet, sensor insertion requires a needle. Patients still must test SMBG about four times per day to calibrate the CGM sensor. This modality is less accurate with low or rapidly rising glucose. CGM is also not widely available, due to cost and insurance issues. A non-invasive glucose monitor was discontinued due to problems with accuracy and tolerability. Compounding these challenges is the surging number of individuals with diabetes mellitus. Every 19 seconds, an American 20 years of age or older is diagnosed with DM. There is thus an unmet need for a non-invasive glucose monitoring device. UC San Diego nanoengineers developed a flexible, ultra-thin sensor adherent to the skin, similar to a temporary tattoo. Preliminary data from seven individuals without DM demonstrated correlation between glucose measurements from this sensor and a glucometer. This study will evaluate the sensor in participants with diabetes mellitus, comparing their glucose levels as detected by a tattoo sensor with corresponding SMBG.

Farhad Imam, MD, PhD Farhad Imam, MD, PhD
UC San Diego Department of Medicine
Department contributed to pilot project funding

Title: Untargeted, Large-Scale Metabolomics in Neonatology for Disease Biomarker Discovery

We aim to discover an association between specific metabolites and a wide variety of common neonatal diseases including prematurity, hypoxic ischemic injury, meconium aspiration syndrome, neonatal abstinence syndrome, Persistent Pulmonary Hypertension of the Newborn, congenital heart disease, and others. We plan to apply our recently validated methodology1 to perform an unbiased metabolomic analysis of patient samples, measuring thousands of individual metabolites in the blood in order to better understand the organ systems and biological functions that contribute to diseases pathogenesis and/or progression. We hope to identify a unique metabolite signature for each of these diseases. Furthermore, we plan to use metabolic pathway analysis to determine whether differentially regulated metabolites are indicative of a change in a specific signaling pathway or gene, such as in the well-established case of congenital adrenal hyperplasia and particular steroid intermediates. We will use waste blood leftover from samples drawn at our participating hospitals for routine laboratory investigations and thereby not expose patients to additional risks and/or procedures.

Daniel Simpson, MD Daniel Simpson, MD
UC San Diego Department of Radiation Medicine & Applied Sciences
Department contributed to pilot project funding


Title: Restriction Spectrum Imaging for Pre-surgical Assessment of Neoadjuvant Treatment Response in Rectal Cancer

Trimodality therapy with neoadjuvant chemoradiation followed by radical surgical resection of the rectum is the standard of care for locally advanced rectal cancer. Radical surgery to remove the rectum, although effective, comes with significant perioperative and postoperative morbidity and can be associated with decreased quality of life, especially in patients undergoing abdominoperineal resection who are all left with a permanent colostomy. Multiple institutions have published promising results in patients treated with a “watch and wait” strategy in which observation is employed among select patients who demonstrate a good response to neoadjuvant therapy, and radical resection is reserved for salvage. One critical issue is assessment of treatment response to identify which patients may be spared surgery. Unfortunately, current clinical and radiographic techniques for assessing treatment response are inaccurate.

Restriction spectrum imaging (RSI) is a novel advanced MRI diffusion technique originally developed for detection of brain tumors and modified for extracranial tumor detection that offers several potential advantages over traditional imaging techniques, including improved tumor conspicuity, improved specificity for differentiating tumor from inflammation, and decreased geometric distortion. Thus, RSI may improve the diagnostic accuracy of pre-surgical assessment of treatment response in rectal cancer.

This study will evaluate tumor response following neoadjuvant chemoradiation using our novel RSI technique and correlate imaging findings with pathologic specimens following surgery. The aim is to use RSI to examine chemoradiation-induced changes within pre-specified regions of interest (ROI) within rectal tumors. We will measure the mean cellularity index within ROIs to determine if there are detectable changes between pre- and post-treatment images. The second aim is to determine the association between radiographic response by RSI and pathologic response. We will measure the pre-surgical cellularity index within pre-specified ROIs and correlate these with matched histopathologic regions within the excised tumor specimen.

Collaborating are Lisa Parry, MD, Department of Surgery; David Karow, MD, PhD, Department of Radiology; and Mark Valasek, MD, PhD, Department of Pathology.

Translational Research Pilot Projects

Eric Adler, MD Eric Adler, MD
UC San Diego Department of Medicine
Department contributed to pilot project funding
*Also received Daniel O’Connor Award

Title: Preclinical Gene Therapy Study for the Treatment of Danon Disease

Danon disease is an X-linked disorder caused by mutations in the gene encoding lysosome-associated membrane protein type-2 (LAMP-2). LAMP-2 localizes to the lysosomal membrane and is critical for autophagosome-lysosome fusion. LAMP-2 deficiency results in impaired autophagic flux, accumulation of toxic cellular contents, and apoptosis. Clinically, Danon disease is characterized by skeletal muscle weakness, hypertrophic cardiomyopathy, and mild cognitive impairment. Over time, Danon patients develop progressive cardiac fibrosis, ventricular arrhythmias, and end-stage heart failure and typically die in their 20s without heart transplantation. Currently, there are no FDA-approved therapies for the treatment of Danon disease.

Our lab previously characterized Danon disease in vitro (Hashem et al., Stem Cells, 2015) using induced pluripotent stem cell (iPSC) lines generated from Danon patients. We showed that Danon iPSC-derived cardiomyocytes (iPSC-CMs) recapitulated key phenotypic abnormalities seen in Danon patients including: accumulation of immature autophagic vacuoles, elevated reactive oxygen species (ROS) levels, fragmented mitochondria, and increased apoptosis. These abnormalities were completely reversed by overexpressing LAMP-2 in a virally transfected Danon iPSC rescue line with inducible LAMP-2 expression under the control of a doxycycline promoter, a finding that supports the feasibility of gene replacement therapy for treating Danon disease. Our lab also characterized a colony of LAMP-2 knockout mice. These mice demonstrate phenotypic abnormalities similar to Danon patients such as impaired autophagic flux, mitochondrial dysfunction, cardiac hypertrophy and fibrosis, and skeletal muscle weakness, indicating that they are a faithful model of Danon disease.

This preclinical study tests the efficacy for gene replacement in a Danon mouse model. The project includes evaluation of LAMP-2 gene replacement in LAMP-2 knockout mice, and includes production of an adeno-associated virus delivery vector, experimental design and toxicity studies. We will perform functional, biochemical and histological analyses of the mice. This study could lead to clinical trials in human patients and hope for a disease with no other treatment options.

Collaborators include Ju Chen, PhD, Seaweed Canyon Physiology Laboratory, UC San Diego, and Kirk Hammond, MD, Cardiology, UC San Diego.

Conor Caffrey, PhD Conor Caffrey, PhD
UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences
Department contributed to pilot project funding

Title: Rapid, Point-of-care Diagnosis of Schistosomiasis

Schistosomiasis is a morbid neglected disease caused by the Schistosoma blood fluke that resides in the cardio-vascular system. As many as 300 million people are infected, with 700 million at risk. Children and adolescents are most afflicted, and, if left untreated, the disease causes chronic pain and fatigue that detract from school and work performance, and ultimately, social and economic development. Co-morbidities include bladder cancer and an increased risk of HIV infection in women. The World Health Organization regards schistosomiasis as having a socioeconomic impact that rivals malaria. In sub-Saharan Africa, disease prevalence is estimated at the community level by counting parasite eggs in stool or urine before chemical deworming. Egg-count diagnosis is insensitive, meaning that disease prevalence is seriously under-estimated, and that drug efficacy, including possible drug resistance, cannot be reliably measured. This is a growing concern given recent trans-national agency efforts to expand the deployment of the single drug available for treatment. Finally, egg counting is slow, requires trained personnel, and associated equipment and chemicals. A simpler, accurate and sensitive point-of-care (POC) test is needed if schistosomiasis is to be eliminated.

We will deliver a low cost, simple-to-operate and quantitative diagnostic assay for schistosomiasis. We have the tools required to develop and optimize a new proof-of-concept antigen test with collaborators at MBio Diagnostics. These include the defined parasite antigen, monoclonal antibodies and an animal model of infection. The team also has clinical networks in Africa and Brazil for human blood samples and assay performance testing. The project kick-starts the development of a prototype assay. We will first optimize the assay for dynamic range in whole blood spiked with the parasite antigen and then in mice naturally infected with different worm burdens. Finally, we will test infection-positive and -negative human samples from endemic areas in Brazil.

Soumita Das, PhD Soumita Das, PhD
UC San Diego Department of Pathology
Department contributed to pilot project funding

Title: The Link between MCP-1 and ELMO1: a New Marker in Inflammatory Diseases

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), affect millions of Americans. In IBD, chemokines and cytokines, including TNF-a (Tumor Necrosis Factor-a), IL-1b and CCL2/MCP-1 (Monocyte Chemoattractant Protein-1), are important in the regulation of mucosal inflammation by promoting leukocyte migration. Specifically, MCP-1 is a potent chemoattractant for monocytes. Infection in IBD may promote immune cells to secrete pro-inflammatory mediators and induce chronic intestinal inflammation.

Adherent-invasive E. coli LF82 is one of the major bacteria associated with CD. We found that LF82 is engulfed into host cells by Engulfment and Cell motility protein 1 (ELMO1) on macrophages. ELMO1 is a cytosolic sensor of bacteria, and it interacts with the cell surface receptor Brain-Angiogenesis Inhibitor-1(BAI1), which binds bacterial Lipopolysachharide. ELMO1 facilitates the engulfment of bacteria and induces pro-inflammatory cytokines (including TNF-a, MCP-1 and IL-1b). Accordingly, intestinal macrophages isolated from ELMO1 KO mice showed an ablation of bacterial internalization compared to WT mice. A proteomic profile approach showed that the depletion of ELMO1 in macrophages following infection downregulated MCP-1. Interestingly, the transcriptomic profiling from 3 ileum samples from CD patients, collected from the UC San Diego IBD center under the guidance of Drs. Brigid Boland and William Sandborn, showed higher expression of ELMO1 compared to the healthy control. Thus, we will test the hypothesis in this pilot project that ELMO-1 is up-regulated in CD samples and plays a role in MCP-1 expression and monocyte recruitment. Future support will help to assess if ELMO1 can be an effective therapeutic target in CD.

Anthony O’Donoghue, PhD Anthony O’Donoghue, PhD
Skaggs School of Pharmacy & Pharmaceutical Sciences
Department contributed to pilot project funding

Title: Rapid, Products of Conception (POC) Detection of Candidemia in Serum

Candida albicans is best known for causing common vaginal yeast infections, but entering the bloodstream causes life-threatening infections, known as candidemia. It is rare in healthy people, but is the fourth most common blood infection among hospitalized patients in the U.S. The symptoms are vague and blood cultures are the gold standard for diagnosis. However, C. albicans cultures have a mean time to positivity (TTP) of 34.2 hours while other Candida isolates, which also cause candidemia, have a TTP ranging from 19.9 hours (C.tropicalis) to 56.5 hours (C. glabrata). Candidemia has a 40 percent mortality rate due in part to the long diagnosis time, which often occurs postmortem. A rapid and sensitive tool to detect candida infections in blood has the potential to save lives while also avoiding unnecessary IV antibiotic treatments.

All Candida species secrete a set of aspartyl proteases that are optimally active under acidic conditions. Using a mass spectrometry-based substrate profiling assay, the proteolytic specificity associated with the C. albicans proteases in both planktonic and biofilm cultures were uncovered.  In addition, our proteomic studies have shown that these enzymes are amongst the most abundant proteins secreted by C. albicans. Using these data, we will develop a set of peptide substrates that are specifically cleaved by Candida proteases and not by human blood proteases such as the clotting enzymes.

This project develops a point-of-care assay by tethering a magnetic nanoparticle to a magnetic nanosensor via hexa-peptide linker sequences that will only be cleaved by Candida proteases. Addition of 50 μL of human serum containing trace levels of Candida proteases will release the magnetic nanoparticle producing a real-time, quantitative signal. Each protease molecule can cleave millions of substrate molecules and therefore this activity-based detection will not require additional signal amplification as is common for ELISA and PCR-based detection systems. To suppress serum derived protease activity, we will acidify the sample prior to the measurement. Acidification of serum, in combination with specific substrates for Candida proteases, will ensure that only the proteolytic activity derived from yeast will be detectable. We anticipate that detection of proteases activity would reduce the TTP for candidemia from 1-3 days to less than one hour.

Collaborating with Drew Hall, PhD, Department of Electrical and Computer Engineering at the Jacobs School of Engineering, UC San Diego.

Albert Remacle, PhD Albert Remacle, PhD
Sanford Burnham Prebys Medical Discovery Institute

Title: Potent and Selective Fully Human Recombinant Monoclonal Antibody Against Pro-tumorigenic/Invasive Membrane Type-1 Matrix Metalloproteinase (MT1-MMP)

With more than 230,000 new cases and about 40,000 deaths each year, breast cancer is the most common malignancy in American women. The leading cause of patient death is the brain-liver-bone metastatic spread. Metastatic cells increase the levels of matrix metalloproteinases (MMPs), especially pro-tumorigenic/invasive membrane type-1 MMP (MT1-MMP) to degrade the extracellular matrix and the basement membrane to penetrate into the blood and lymph to distant organs. There is overwhelming evidence that MT1-MMP’s expression directly correlates with poor clinical outcome, blood vessel invasion and distant metastasis in triple-negative (ER, PR, HER2/neu) breast cancer, the deadliest cancer sub-type with limited treatment options. As a result, MT1-MMP-1 has been recognized as an attractive therapeutic target.

High selectivity is a key parameter for the anti-cancer efficiency of MMP inhibitors (MMPIs). Small molecule MMPIs that target the Zn2+ ion in the highly homologous MMP active sites fail to discriminate MT1-MMP relative to other MMPs. Because these MMPis target simultaneously multiple pro-tumorigenic and anti-tumorigenic MMPs, causing then off-target side-effects, they failed clinical trials. Novel, selective and potent, MMPIs targeting MT1-MMP alone are now required. Because of their supreme selectivity, antibody-based inhibitors are emerging as cancer drugs and as an alternative to small-molecule MMPIs.

Contrary to human and murine antibodies with the 9-12 residue short paratopes/complementarity determining regions (CDRs), camelid antibodies are characterized by the 23-27 residue long, flexible CDRs. As a result, camelid-like antibodies represent more potent binders of the enzyme’s active site pocket and more efficient inhibitors of multiple enzyme types. These considerations are especially relevant for MT1-MMP, a collagenase that accommodates the bulky triple helical collagen chain in its sizable, albeit buried, active site cavity.

The most potent and selective MT1-MMP’s inhibitor we have identified in the hybrid human camelid-like Fab library is the 3A2 Fab. The project goals are to mature the synthetic human 3A2 Fab into its full-length IgG format to determine the off-target activity, selectivity and inhibitory potency of the matured 3A2 IgG against MT1-MMP, and to evaluate the anti-tumorigenic potency of the matured 3A2 IgG against solid tumor and metastasis using the relevant in vivo animal model of human breast cancer.
Collaborating with Dr. Xin Ge, UC Riverside

Fiza Singh, MD
UC San Diego, Department of Psychiatry
Department contributed to pilot project funding

Title: Enhancing Gamma Band Response in Schizophrenia Patients to Improve Working Memory

Schizophrenia (SCZ) is a chronic debilitating mental disorder that affects 2.4 million Americans and leads to considerable individual and societal costs. In patients with SCZ, cognitive deficits (CD) occur early in the course of the illness, are associated with more severe illness, and are the best predictor of functional outcomes. Nonetheless, to date, cognitive deficits have been difficult to treat using available treatments. Recent studies suggest CD in patients with SCZ may arise from abnormal synchronization of distributed neural networks. Synchronization binds cortical areas into functional networks in a task and state-dependent manner. Thus novel therapies targeting abnormal neural synchrony may improve previously refractory symptoms.

Neural synchrony in the gamma band (GBR, 30-45Hz) plays a central role in top-down attention, multisensory processing, perceptual binding and working memory (WM). Patients with SCZ exhibit abnormal GBR, and the magnitude of impairment is associated with the severity of cognitive disorganization. Given these results, improving GBR should improve CD, including WM in SCZ. This hypothesis has been tested and confirmed using repetitive transcranial magnetic stimulation (rTMS). Additionally, EEG-based neurofeedback (NFB) is hypothesized to improve GBR and cognitive function in patients with SCZ. NFB is a low-cost, easily administered and well-tolerated treatment. In healthy controls, Gamma-NFB improves GBR and cognitive function including WM.

This project tests the feasibility and effectiveness of improving GBR using gamma-NFB in patients with SCZ. We will compare GBR between healthy controls (HC) and SCZ patients, and conduct an eight-week double-blind, randomized, cross-over neurofeedback pilot study to estimate the effect size of gamma neurofeedback(G-NFB) compared to sham neurofeedback.

Innovative Technology Pilot Projects

Alexandre Gingras, PhD Alexandre Gingras, PhD
UC San Diego, Department of Medicine
Department contributed to pilot project funding

Title: Identification of Small Molecule Inhibitors of Integrin Activation using Nanodiscs

Regulation of the affinity of integrins for adhesive ligands is central to development, cell migration, and assembly of the extracellular matrix. Blood cells, such as leukocytes and platelets, have played a pivotal role in establishing current paradigms of this process, a process that controls platelet aggregation, leukocyte trafficking, and angiogenesis. Blocking these integrins has shown therapeutic promise in a wide variety of diseases including thrombosis, psoriasis, multiple sclerosis, and cancer. That said, mechanism-based toxicities, ascribable to the effects of complete blockade of a particular integrin, have narrowed the therapeutic window of antibody and small molecule inhibitors of ligand binding to integrins. Our project develops an innovative approach to identify partial antagonists of integrins that act by disrupting the transmembrane signals that increase ligand-binding affinity.

Many integrins are expressed in a low affinity form and intracellular signals initiated by agonists acting via distinct excitatory receptors, resulting in increased affinity, often referred to as “activation.” Our studies and those of others showed that the binding of talins to the b subunit cytoplasmic tail is a final common step in integrin activation in vitro and in vivo. Importantly, previous work showed that blocking talin binding to αIIbβ3 can inhibit αIIbβ3 activation and suppress arterial thrombosis in mice with markedly reduced pathological bleeding relative to genetic deletion of αIIbβ3 (i.e. a complete blockade of function).

Studies in the Ginsberg lab reconstituted the final step of talin induced αIIbβ3 activation in vitro with integrin nanodiscs in which a single integrin is inserted into a 10-12 nm diameter lipid bilayer encircled by engineered membrane scaffold protein (MSP). Our studies showed that talin binding is sufficient to induce an allosteric rearrangement of the extracellular domain that increases the affinity of αllbβ3. Talin activates αllbβ3 integrins by simultaneously binding to phospholipids and the β3 tail. Later studies, using fluorescence reporters of the embedding of the integrin β3 TMD showed that talin acts by changing the topology of this TMD.  Based on these findings we propose to develop novel screens for small molecule partial integrin antagonists that act by preventing talin-mediated changes in the topology of the β3 TMD.

Shelley Lawrence, MD, MS Shelley Lawrence, MD, MS
UC San Diego, Department of Pediatrics/Rady Children’s Hospital
Department contributed to pilot project funding

Title: High-resolution Melt with Machine Learning for the Accurate Diagnosis of Neonatal Sepsis

The isolation and identification of pathogenic bacteria by blood culture remains the “Gold Standard” for the diagnosis of sepsis, but sensitivity in neonates (less than 28 days of life) remains poor. Although the majority of sepsis evaluations are completed in the first 48 hours of life, less than 1 percent of blood cultures will become positive. The likelihood of obtaining a positive culture is hampered by the administration of empiric intrapartum antibiotics to more than one-third of laboring women and decreased total blood volume in neonates available for testing. Routine cultures are also hampered by prolonged delays in pathogen identification and antibiotic sensitivity analysis (up to 4-5 days), leading to unnecessary exposure of non-infected infants to broad-spectrum antibiotics, bacterial antibiotic resistance, invasive fungal infections, death, necrotizing enterocolitis, and length of stay.

Nucleic acid characterization using automated High Resolution Melt (HRM) provides a simple, low cost, rapid, and robust method for genotyping bacterial sequence variations and provides a modern alternative to blood culture testing. By measuring the fluorescence of a saturating intercalating dye as PCR-amplified DNA/RNA fragments are heated and disassociate, sequence defined melt curves are generated with single-nucleotide resolution in a closed tube reaction, for the identification of mono or polymicrobial infections. Using machine learning technology to create unique bacterial “fingerprints,” we can correctly identify disease-causing pathogen(s) with an accuracy of 99-100 percent. Transitioning this approach to a digital PCR format facilitates the accurate identification of mixed infections. Because DNA and RNA are both amplified, we can precisely and expeditiously capture both deceased and replicating bacteria with a turnaround time of two hours using minimal blood volume (1 mL) from cord blood or the neonate. This project studies the accuracy and validity of HRM as a test for the diagnosis of neonatal sepsis, and evaluates HRM’s ability to detect and rapidly identify pathogens in comparison with blood culture. Our aims are to establish melt curves for pathogens most often associated with neonatal infection; to develop an instrument to carry out digital HRM analysis on high-content digital PCR chips for analysis of neonatal blood samples; and to perform analytical and clinical performance evaluations of our integrated digital HRM platform.

Collaborating with Drs. Stephanie Fraley and Todd Coleman from the UC San Diego Department of Bioengineering and Dr. Victor Nizet, pediatric infectious disease specialist, UC San Diego.

Academic-Community Pilot Projects

Amy Lansing, PhD Amy Lansing, PhD
UC San Diego, Department of Psychiatry

Community Partner:
Sacha Sykora, MA
SIA (School for Integrated Academics & Technologies) Tech High School, El Centro

Title: School-based Trauma-Informed System (TIS) Implementation: Trauma-Responsiveness and Cognitive Capacity Building in Imperial County

The School for Integrated Academics and Technologies (SIATech) is a national Alternative Education (AltEd) provider that serves approximately 2,500 re-engaged students (ages 16-24 years old) who have faced a variety of adversities, including behavioral and substance problems, trauma exposure, poverty, and teen pregnancy. In rural communities, such as Imperial County’s El Centro district, many families are headed by migrant working parents, whose mobility to sustain their families increase the risk for their children to drop out of high school. AltEd settings provide an important second chance for a high-school diploma or GED to improve functional outcomes for these re-engaged students, ages 16-24. This project will develop an Academic-Community Partnership with SIATech aimed at decreasing a second-chance dropout and improving student engagement in their El Centro school. This will consist of: gathering stakeholder (students, teachers, staff, executive leadership) input through focus groups to illicit their specific needs in a rural school community; holding stakeholder feedback sessions in order to tailor a compensatory cognitive intervention aimed at improving school readiness skills often missing in dropout populations; and adopting evidence-based practices to improve the learning environment by implementing a trauma informed system (TIS) through teacher, staff and leadership training and professional development. We will measure organizational readiness for change, as well as school culture, climate and engagement before and after implementation, to estimate the impact of TIS training on the El Centro school setting and will analyze focus group data to ascertain the feasibility of implementing a compensatory cognitive intervention tailored for their students. Adaptation of this tailored intervention and of incorporation of TIS practices will provide a framework for use in rural districts nationwide. Findings will be presented nationally and dispersed through SIATech’s existing partnership network and at the annual national AltEd Alternative Accountability Policy Forum.  Additional funds will be sought to continue the partnership and implement similar practices and tools in other AltEd school systems. 

Additional investigators include:  Audrey Beck, PhD, and Sheldon Zang, PhD, San Diego State University, Department of Sociology

Elizabeth Reed, ScD, MPH Argentina Servin, MD, MPH
Zara Marselian, MA, FACHE Julia Macouzet

Elizabeth Reed, ScD, MPH
Argentina Servin, MD, MPH

UC San Diego, Department of Medicine, Division of Global Health



Community Partner:
Zara Marselian, MA, FACHE, Executive Director
Julia Macouzet, Financial Empowerment and Family Care Advocate
La Maestra Community Health Centers

Title: Jardines Verdes: Microfinance Businesses to Prevent Obesity and Related Health Conditions among Latinos in San Diego, CA

Food insecurity, defined as having limited access to adequate food, has been shown to reduce dietary quality, affect nutritional intake, and has been associated with obesity and related health morbidity (e.g., type 2 diabetes, hypertension). In 2014, in the U.S., 48.1 million lived in food insecure households, including 32.8 million adults and 153.3 million children. Racial/ethnic disparities are notable, with Latinos experiencing disproportionately higher rates of food insecurity and obesity-related conditions compared to Whites. Children who are obese are at high risk for cardiovascular health concerns, pre-diabetes, and bone and joint problems. Overweight and obese children have increased risk for developing health problems as an adult including heart disease, type 2 diabetes, stroke, cancer and osteoarthritis. Efforts are needed to address this critical public health concern.

Food insecurity is largely attributed to poverty, and poor households experience the highest rates of obesity and related health conditions in the United States. Poverty is a primary factor contributing to excess consumption of foods and beverages with low nutritional value. Additionally, many families living in poverty experience a number of other constraints that affect the types of foods and beverages consumed. Thus, economic promotion may be an important, yet understudied, strategy to address the intersecting issues of poverty, food insecurity, and obesity among low-income families. In particular, microfinance programs (providing small business loans to women) have been effective in increasing household financial security, and shown to improve a number of other related health conditions stemming from poverty.

Specifically, in San Diego by the U.S.-Mexico border, one third of the population is Latino, one-quarter have household incomes less than 200 percent of the Federal Poverty Level (FPL), and 14 percent of the population living in San Diego County experience food insecurity. San Diego County also has one of the highest childhood obesity rates in California. This project aims to pilot a microfinance intervention that includes community garden access and a nutrition skills training component among low-income Latino families seeking health services from La Maestra clinics in City Heights, San Diego, where Latinos comprise half of the population, one quarter experience food insecurity, and greater than 50 percent of the community members have household incomes of less than 185 percent of FPL.

Dissemination and Implementation Research Pilot Project

Jeanne Huang, MD, MPH Jeanne Huang, MD, MPH
Department of Pediatrics, University of California, San Diego

Community Partner:
Javier Rodriguez, MD
La Maestra Community Health Centers

Title: Improving Pediatric Hepatitis B Screening in High-Risk San Diego Communities

Hepatitis B virus (HBV) has infected an estimated 2 billion persons worldwide of which more than 350 million persons have chronic, lifelong infections. In the U.S., 1.25 million persons suffer from chronic HBV infection. Hepatitis B chronic liver disease costs an estimated $1.3 to 1.5 billion health care dollars in the U.S. alone expended annually from 2003-2006 on hospitalization costs. Acquisition of chronic HBV is greatest through perinatal and early childhood exposures. However, early in life, chronic HBV is frequently asymptomatic. Therefore, the CDC recommends that all individuals born in geographic regions with an HBsAg prevalence of >=2 percent should be screened. Most of the world’s population lives in regions qualifying for HBV screening per these recommendations. The CDC recommends that children born in the US to immigrant parents from these endemic areas should be screened. Also, all children born to HBsAg+ mothers and children who live in a household with a known HbsAg+ person should be screened. Once identified, children with chronic HBV should consult with a pediatric liver specialist and be monitored for complications or progression of disease every 6 to 12 months.

In the Greater San Diego region, there are potentially over 5,500 affected youth not being actively followed for chronic HBV. We suspect that this reflects poor performance of published screening guidelines and thus submit that improvement in clinician awareness of screening guidelines for HBV is needed among clinicians who treat at-risk youth in the San Diego area.

We are developing and disseminating a Maintenance of Certification (MOC) Quality Improvement project to improve the performance of evidence-based guidelines for the screening of youth exposed to hepatitis B via perinatal or childhood exposures. MOC is a recently implemented process for physician certification maintenance through approved medical specialty boards of the American Board of Medical Specialties. The developed QI project will be delivered via the web to physicians who care for at-risk pediatric populations in San Diego. We will evaluate the project and its effect on clinician performance of HBV screening in at-risk youth from affected San Diego communities.

Collaborators include Robert Gish, MD, consultant and Binh Tran, PharmD, MS, MBA, Asia Pacific Health Foundation

*The Daniel T. O’Connor Memorial Award was created to support a junior investigator by supplementing a CTRI pilot project. O'Connor, a longstanding and beloved member of the faculty of the UC San Diego School of Medicine, had been a former chair of the CTRI Research Committee and had conducted many clinical trials at CTRI. He died in 2014. O’Connor’s widow, Kellie Evans-O’Connor, established the award.