19 Feb CTSI Announces Pilot Award Recipients for 2013
The CTSI scientific community has come together once again to work in partnership in multidisciplinary research teams to discover clues that will lead to better treatments and cures for today’s medical threats. CTSI cultivates an interdisciplinary spirit where physicians, biologists, engineers, chemists and many other scientists across multiple disciplines can work hand-in-hand toward a common goal to accelerate research discoveries and provide better ways in which we approach medical treatments.
CTSI will fund a total of sixteen new research projects through its Pilot and Collaborative Clinical and Translational Research Grants Program.This year our scientist will concentrate their efforts on studies from post-stroke and PTSD treatments to Breast Cancer and early detection of rejection following pediatric heart transplantation to name a few.
These projects aim to create synergy through interdepartmental and inter-institutional collaboration and are specifically designed to lead to major future research support (i.e., PPG, SCORE, or large multi-PI interdisciplinary RO1 projects). The studies will explore the multidisciplinary and clinical potential of promising mechanistic findings that have the potential to be translated into improvements to clinical practice and community health.
The Pilot and Collaborative Clinical and Translational Research Grants Program advocates, facilitates and fosters the continuum of research from bench to bedside and from bedside to community practice. Support for the 2013 Pilot Award Program comes from Advancing a Healthier Wisconsin (AHW), the National Institutes of Health (NIH) and the MCW Cancer Center.
Multi-scale Pharmacokinetic modeling of Imaging Biomarkers for Assessing Acute Lung Injury
PI: Said Audi, PhD, Marquette University; Daniel Beard, PhD, Medical College of Wisconsin
Co-PIs: Ann Clough, PhD, Marquette University; Brian Carlson, PhD, Medical College of Wisconsin
Acute lung injury (ALI) is one of the most frequent causes of admission to the intensive care unit. Despite many studies aimed at understanding the mechanisms involved in ALI, the clinical course of patients with this condition is still widely variable. An important contributing factor to this variability is the lack of an effective clinical means for early detection of ALI, which delays the implementation of optimal therapies. The proposed research is significant, because it will establish a mechanistic and quantitative basis for utilizing two clinically approved biomarkers for early detection of ALI, and for rapid translation to clinical diagnostics. Furthermore, it will provide direct information regarding the toxic effects of hyperoxia on the lung uptake of these biomarkers. Thus our long term goal is to develop a clinical means for early detection of ALI, which will enhance diagnosis of ALI, influence the choice of therapy, and as a result improve outcome.
Pilot Intestinal Microbiota and the Pathogenesis of Cardiovascular Disease
PI: John Baker, PhD, Medical College of Wisconsin
Co-PIs: Shailendra Patel, MD, Medical College of Wisconsin/Zablocki VA Medical Center; Michael Widlansky, MD, Medical College of Wisconsin; Nita Salzman, MD, PhD, Medical College of Wisconsin/Children’s Hospital of Wisconsin; Nanda Venu, MD, Medical College of Wisconsin
We have discovered a new pathway that links the type of bacteria present in the intestines and susceptibility to, and the severity of, heart attacks. The study is novel and important because it is the first time that anyone has shown a probiotic bacterium (live microorganism beneficial to its host) that lives in the intestines and suppresses leptin production, may be managed in order to reduce the risk of a heart attack and the injury suffered from a heart attack. This may provide opportunities for novel diagnostic tests as well as a potential for therapeutic intervention. Our objective is to determine whether leptin levels are decreased and endothelial cell function increased by a probiotic and an antibiotic in patients with established coronary artery disease.
Assessment of Coupling between Mass Neural Activity and the Hemodynamic Response on Humans
PI: Scott Beardsley, PhD, Marquette University
Co-PIs: Einat Liebenthal, ScD, Medical College of Wisconsin
The proposed research aims to characterize the normative relationship between mass neural activity (measured with EEG and MEG) and the hemodynamic BOLD response (measured with fMRI) in a network of brain regions engaged in auditory and speech perception. The goal is to quantify the form and extent of nonlinear relationships between the BOLD response and EEG/MEG measures in these areas, and the impact of experimental design choices on the relationship.
Design of Immunomodulatory Peptides from the HTLV-2 Tax Protein
PI: Mark Beilke, MD, Medical College of Wisconsin
Co-PIs: Jimmy Feix, PhD, Medical College of Wisconsin
The human T leukemia virus types 1 and 2 (HTLV-1, HTLV-2) genomes share a high degree of homology but differ significantly with respect to their ability to cause disease. Unlike the human immunodeficiency virus (HIV-1), neither HTLV-1 nor HTLV-2 cause AIDS. HTLV-1 is the causative agent of adult T cell leukemia/lymphoma (ATLL), tropical spastic paraparesis/HTLV-1 associated myelopathy, HTLV-1 associated uveitis, and a number of autoimmune disorders. In contrast, HTLV-2, which infects injection drug users (IDUs) in epidemic numbers, is generally a silent and asymptomatic infection. Of interest, when HTLV-2 co-infects HIV-1 infected IDUs, dually infected individuals often have delayed rates of CD4+ T cell decline and attenuated progression to AIDS. Through this work, we hypothesize that oligopeptides can be designed which have targeted effects on host cell gene expression with potentially beneficial immunomodulatory effects. The long term goal will be to develop candidate molecules with low toxicity to host cells and with specific action on various arms of innate immune responses against viral pathogens such as HIV-1.
Development of Novel Therapeutics for Triple Negative Breast Cancer
PI: Guan Chen, MD, PhD, Medical College of Wisconsin
Co-PIs: Xiao-Mei Qi, MD, Medical College of Wisconsin; Christopher Chitambar, MD, Medical College of Wisconsin; Zainab Basir, MD, Medical College of Wisconsin/Froedtert Hospital
Triple negative breast cancers (TNBC) lack expression of estrogen receptor (ER), progesterone receptor (PR), and Her-2 (Erb2), and consequently have no established targets for therapeutic development and treatment. As a result, TNBC has the worst prognosis among all types of breast cancers in clinic and there is an urgent need to identify new targets for therapeutic exploration. The goal of this grant proposal is to demonstrate that p38γ MAPK (mitogen-activated protein kinase) is a TNBC oncogene and its pharmacological inhibitor pirfenidone (PFD) will be therefore a novel therapeutic agent for TNBC.
mPeer: Mobile Detection of High Risk Behavior in Veterans- A Sociotechnical Systems Approach
PI: Zeno Franco, PhD, Medical College of Wisconsin
Co-PIs: Sheikh Iqbal Ahamed, PhD, Marquette University; Jeffrey Whittle, MD, MPH, Medical College of Wisconsin/Zablocki VA Medical Center; Christina Eldredge, MD, Medical College of Wisconsin; Terri deRoon-Cassini, PhD, Medical College of Wisconsin; Bob Curry, Director, DryHootch of America
Veteran mental health is an increasingly significant national problem given the large number of returning veterans from the recent war in Iraq and continued military presence in Afghanistan. Consensus prevalence estimates suggest that Post Traumatic Stress Disorder (PTSD) impacts between 15-20% of the veteran population. Despite recent advances in evidence based care for PTSD undertaken by the Veteran Health Administration (VA), the disorder is typically chronic and treatment resistant. This pilot project will use a mobile health (mHealth) based behavioral informatics approach to detect high risk behavior using existing smart phone technologies. We will link this basic science effort to a community-based outreach program in Milwaukee capable of recruiting a non-clinical sample of veterans at likely to prospectively engage in high risk behaviors to obtain exploratory and confirmatory data set. This method will create a framework for a robust sociotechnical system capable of delivering personalized behavioral intervention for this population.
Parent/Nurse Controlled Analgesia for Post-Operative Pain Management in neonates: A Preliminary Randomized Controlled Trial
PI: Keri Hainsworth, PhD, Medical College of Wisconsin
Co-PIs: Michelle Czarneck, RN-BC, MSN, CPNP, Children’s Hospital of Wisconsin; Marjorie Arca, MD, Medical College of Wisconsin/Children’s Hospital of Wisconsin; Michael Uhing, MD, Medical College of Wisconsin/Children’s Hospital of Wisconsin; Pippa Simpson, PhD, Medical College of Wisconsin/Children’s Hospital of Wisconsin; Steven Weisman, MD, Medical College of Wisconsin/Children’s Hospital of Wisconsin
This randomized controlled trial will compare PNCA to COI for the following outcomes: opioid consumption, pain scores, the need for additional sedation (benzodiazepines), frequency of opioid tolerance as measured by the need for transition to methadone use, and frequency of adverse events including somnolence, respiratory depression, naloxone administration, and reintubation. In addition, nursing and parent satisfaction will be evaluated. This is the first known RCT regarding PNCA and COI evaluation and will allow clinicians and researchers the opportunity to reveal the advantages of implementing PNCA in the NICU which in turn, may improve patient care and will allow for the design of a multi-site study to provide unequivocal support.
Highly Sensitive Non-Invasive Method to Monitor Transplant Rejection
PI: Mats Hidestrand, PhD, Medical College of Wisconsin
Co-PIs: Michael Mitchell, MD, Medical College of Wisconsin; Steven Zangwill, MD, Medical College of Wisconsin/Children’s Hospital of Wisconsin; Pippa Simpson, PhD, Medical College of Wisconsin/Children’s Hospital of Wisconsin;Aoy Tomita-Mitchell, Medical College of Wisconsin; Karl Stamm, Marquette University
Early detection of rejection following pediatric heart transplantation facilitates treatment that directly improves clinical outcomes. Frequent monitoring of rejection status is therefore an integral part of post- transplant care and guides therapy and treatment. The current gold standard for rejection monitoring in cardiac transplant patients is by catheter based endomyocardial biopsy which is invasive and associated with risk. It is especially difficult to perform in a pediatric population. We will test a highly innovative approach to monitor rejection using a targeted DNA sequencing method of detection and quantification of donor specific cf-DNA and ascertain its desirable properties which from preliminary data look very promising.
Inflammatory Markers, Physical Fitness and Pain in Children
PI: Marie Hoeger Bement, PhD, PT, Marquette University
Co-PIs: Amy Drendel, DO, Medical College of Wisconsin/Children’s Hospital of Wisconsin; Stacy Stolzman, MPT, Marquette University; April Harkins, PhD, Marquette University; Paula Papanek, PhD, Marquette University; Steve Weisman, MD, Medical College of Wisconsin/Children’s Hospital of Wisconsin
The prevalence of childhood obesity has recently peaked in the USA with ~17% of children considered obese. Along with this obesity epidemic, pain management is a major problem because 50% of obese children regularly experience pain. The coexistence of pain and obesity can impact functional status, decrease health related quality of life, and contribute to a sedentary lifestyle which further increases obesity along with its comorbidities. With the increase in adiposity that occurs with weight gain, a persistent low-grade inflammatory state is created. Understanding the relation between adiposity and inflammation is an important concept because inflammatory markers influence insulin sensitivity, glucose metabolism, and atherosclerosis ultimately leading to impaired health. This study aims to understand the impact of physical fitness and obesity on clinical and experimental pain in children, including potential mechanisms such as elevated inflammatory markers.