CCTS Pilot Grant Projects Funded
Summer 2011 Pilot Grant Projects Funded
The UIC Center for Clinical and Translational Science (CCTS) is pleased to announce that it has awarded funding to two projects in its Summer 2011 Pilot Grant Program. The program is devoted to clinical and translational research – specifically, in this round: (1) Strategic Research Initiatives; and (2) Community Research.
Over forty letters of intent were submitted, and approximately half were selected to submit full proposals. The funded projects include investigators from 12 different departments within 9 colleges.
The Summer 2011 CCTS Pilot Grant Recipients are:
“Pathways to Preterm Birth: Stress, Inflammation, & Cervical Remodeling”. PI: Rosemary White-Traut, Professor, Women, Children and Family Health Science, CON; Co-Investigators: Jacques Abramowicz, Professor, Obstetrics and Gynecology, Rush University; Timothy Bigelow, Assistant Professor, Electrical/Computer Engineering, Iowa State University; Carol Braunschweig, Associate Professor, Kinesiology and Nutrition, AHS; Sue Carter, Professor, Psychiatry, COM; Barbara Dancy, Professor, Health Systems Science, CON; Christopher Engeland, Assistant Professor, Periodontics, COD; Carmen Giurgescu, Assistant Professor, Women, Children and Family Health Science, CON; Mary Dawn Hennessy, Assistant Professor, Women, Children and Family Health Science, CON; Michelle Kominiarek, Assistant Professor, Obstetrics and Gynecology, COM; Barbara McFarlin, Assistant Professor, Women, Children and Family Health Science, CON; Kathleen Norr, Professor, Women, Children and Family Health Science, CON; William O'Brien, Professor, Engineering, UIUC; Annie Qu, Associate Professor, Statistics, UIUC; Ed Wang, Research Assistant Professor, Health System Sciences, CON; and Shannon Zenk, Assistant Professor, Health Systems Sciences, CON. [Show Summary/Hide]
For “Pathways to Preterm Birth: Stress, Inflammation, & Cervical Remodeling”.
This pilot will provide essential data for a program grant submission to determine the pathways that result in preterm birth among African American (AA) women. The preterm birth rate for AA women is currently 17%, over 1.5 times the non-Hispanic white rate. This health disparity has persisted despite decreases in prematurity rates for both AA and non-Hispanic Whites. Prematurity is the leading cause of infant mortality,morbidity, and suboptimal infant development. In 2007, over 500,000 infants were born prematurely (< 37 weeks gestation) at a cost of over $26 billion. The etiology of preterm labor and the disparity for AAs remains unknown.
For the program grant, four studies will explore potential proximal causes of preterm birth among AAs living in Chicago communities. Using integrated data from all four studies, overall pathways will be identified. The first two projects focus on the impact of race-related stressors as a potential pathway to preterm birth for African Americans. Giurgescu (PI) examines the experiential and behavioral responses to stressors, along with inflammatory biomarkers, that predict preterm birth. Kavanaugh (PI) examines qualitatively 40 pregnant women's and their significant other's perceptions of the pregnant women's stresses and resources and integrate this qualitative data. A complimentarity mixed methods approach will integrate these qualitative experiences with Giurgescu's quantitative measures. Hennessy (PI) examines the impact of inflammation, hepcidin, and iron on preterm birth. McFarlin (PI) examines the process of cervical (collagen) remodeling during mid-to-late pregnancy. Cervical remodeling is a central cause of preterm labor that occurs early in the uterine preparation for labor. This project will examine the temporal pattern of cervical remodeling and its relationships to preterm birth, stress, nutrition, and inflammatory responses measured in the first three studies. These four projects were selected because individually they evaluate the critical indicators of stress, nutrition, inflammation and cervical remodeling hypothesized to lead to preterm birth and together they will identify the protective and risk factors for preterm birth.
Our team has established the feasibility and acceptability of this complex protocol for AA pregnant women from a very small pilot study funded by the College of Nursing. However, we need additional pilot data for the quantitative measures to provide power estimations and robust preliminary data to support the program application. We received consultation from the Community Engagement and Research Core's Community Advisory Engagement Board to plan the implementation of the research within the Chicago communities.
Proposed Pilot Aims:
1. To collect questionnaires, biomarkers, cervical ultrasounds and medical record data for a sample of 40 women; combined with the data from our current pilot, this will provide robust pilot data and permit a power-based estimation of effect size for our program grant application.
2. To establish the feasibility of collecting these complex data using the resources of the CRC, CCTS (REDCap), and to work out logistical issues such as blood sample processing and transport.
3. Recruit additional high-risk samples from the maternal-fetal medicine and other prenatal clinical sites at UICMCC and examine prematurity rates from this sample.
“Pilot trial assessing the ability of ezetimibe to improve HCV therapy response”.
PI: Susan Uprichard, Assistant Professor, Hepatology, COM; Co-PI: Scott Cotler, Professor, Hepatology, COM; Co-investigators: Michelle Martin, Clinical Assistant Professor, Pharmacy Practice, COP; and Harel Dahari, Research Assistant Professor, Hepatology, COM. [Show Summary/Hide]
For “Pilot trial assessing the ability of ezetimibe to improve HCV therapy response”.
Although acute hepatitis C virus (HCV) infection is typically asymptomatic, ~80% of patients fail to clear the virus resulting in chronic infection, which can result in cirrhosis and hepatocellular carcinoma (HCC).Consequently, increases in HCV cirrhosis have played a major role in the recent rise of HCC. Importantly, with ~180 million people infected, no vaccine to prevent infection, and only a subset of patients responding to current treatment options, the rate of HCV-associated liver disease is projected to continue increasing creating an immediate need for new, more effective HCV antivirals. In particular, HCV entry represents a promising multi-faceted opportunity for drug discovery; however, antivirals targeting HCV entry are not yet available. As such, our long term goal is to elucidate the molecular details of HCV entry, develop therapeutics to prevent viral entry, and test the efficacy of those inhibitors for treating HCV infection. Toward this end, work in our laboratory has led to the exciting discovery that the Niemann-Pick C1 Like-1 (NPC1L1) cellular cholesterol uptake receptor is required for HCV entry into cells. Furthermore, we have found that ezetimibe, a drug that inhibits NPC1L1-mediated cholesterol uptake and is thus FDA-approved as a lipid lowering agent for treatment of hypercholesterolemia, potently blocks HCV entry in cultured human hepatoma cells and human hepatocytes transplanted into mice. Relevant to this proposal, when used in combination with IFN to treat chronically HCV infected cells both in vitro and in mice, ezetimibe synergistically enhanced inhibition of HCV compared to IFN alone. These results not only shed light on a new mechanism of HCV entry, but also suggest that ezetimibe (Zetia®) might be useful for the treatment of HCV.
As such, the objective of this translational pilot study is to assess the efficacy of ezetimibe as an additional therapeutic agent in patients undergoing treatment for chronic HCV infection. Based on preliminary data, we hypothesize that when included as part of the treatment regimen that the HCV entry inhibitor ezetimibe will augment the 2nd phase decline in HCV viremia in chronically infected patients. As IFN continues to remain the backbone of HCV therapy, we propose to focus on treatment-experienced patients to determine the effectiveness of EZE in improving HCV inhibition kinetics in the context of a suboptimal IFN response. Hence, we have assembled an interdisciplinary team of basic researchers, mathematical modelers, and clinicians to execute the pilot clinical testing required to determine whether addition of ezetimibe to pegIFN-based HCV therapy can increase early treatment response kinetics in HCV treatment-experienced patients that did not respond to therapy previously.
Importantly, the results of this pilot study will not only determine if larger scale clinical trials are justified for the re-indication of ezetimibe for the treatment of HCV and provide the preliminary data necessary to obtainextramural funding for those studies, but also provide the opportunity for the basic and clinical HCV researchers at UIC to execute their first bench-to-bedside translational project, which will hopefully serve as a stepping stone to facilitate similar collaborations in the future.