CTSI Announces the 2015 Pilot Awardees
The CTSI scientific community has come together once again to work in partnership in interdisciplinary research teams to enhance discoveries leading to better treatments and cures for today’s medical threats. CTSI seeks to cultivate inter-institutional and interdisciplinary collaboration between clinical and basic biomedical scientists, social scientists, ethicists, engineers, biostatisticians, informatics specialists, and all members of clinical health care delivery teams.
CTSI will fund a total of seventeen new research projects through its Pilot and Collaborative Clinical and Translational Research Grants Program. This year’s investigative teams will conduct research in order to prevent or treat Left Ventricular Assist Device (LVAD) thrombosis; provide insight into vaccine designs to rejuvenate aged immune systems; identify best practices that will ensure the long-term viability of Milwaukee County’s first pilot Mental Health Court (MHC); build highly selective and potent anti-inflammatory compounds suitable for the clinical treatment of sepsis; and many more.
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 2015 Pilot Award Program comes from Advancing a Healthier Wisconsin Research and Education Program (AHW REP).
Prematurity 101: mHealth Enhanced Prenatal Education
PI: Mir Basir, MD, MS, Medical College of Wisconsin
Co-Investigators: Sheikh Iqbal Ahamed, PhD, Marquette University; Una Olivia Kim, MD, Medical College of Wisconsin; Cresta Jones, MD, Medical College of Wisconsin; Kris Barnekow, PhD, University of Wisconsin—Milwaukee; Michael Lund, MD, Medical College of Wisconsin; Shannon Dreier, MBA, Parent Representative
Knowledge of problems and outcome of premature infants is necessary for parents with threatened preterm delivery to make informed medical-care decisions regarding mode of delivery, neonatal resuscitation, and neonatal intensive care. Studies show that it is challenging to effectively provide complex information to parents in preterm labor. Low health literacy of the general population and poor parental baseline knowledge of prematurity contribute to the difficulty. This study will develop a mHealth educational app containing prematurity-related fetal and neonatal information for parents at risk of premature delivery, and pilot the mHealth app during the prenatal period among parents determined by their obstetric provider to be at risk for premature delivery. Parents will become familiar with complex concepts like fetal viability, resuscitation related decision-making, parental rights to determine aggressiveness of care in cases of significant medical uncertainty. If and when the pregnancy results in preterm labor, parents would have already built a foundation of knowledge and during hospitalization, when parents receive more specific information, they will better comprehend the medical facts, be aware of their rights and obligations and able to effectively advocate for care aligned with their values.
Evaluating the Role of Infection and Neutrophil Extracellular Traps in the Pathophysiology of Ventricular Assist Device Thrombosis
PI: Lisa Baumann Kreuziger, MD, MS, BloodCenter of Wisconsin
Co-Investigators: Nunzio Gaglianello, MD, Medical College of Wisconsin; Alan Mast, MD, PhD, BloodCenter of Wisconsin
Left ventricular assist device (LVAD) thrombosis is a devastating complication that can cause stroke or hemodynamic collapse. Current prevention and treatment strategies for LVAD thrombosis carry significant risk of major hemorrhage. The underlying pathophysiology and initiating event of LVAD thrombosis has not been established. Through collaboration between advanced heart failure cardiology at MCW, hematology and the basic scientists at BCW we will evaluate infection and neutrophil activation as potential mechanisms of LVAD thrombosis. Neutrophil activation and production of neutrophil extracellular traps (NETs) have been found to underlie venous thrombosis. Establishing NETs or infection as the driver of thrombosis would allow targeted treatment with DNAse or potential prevention of thrombosis with antibiotics. Preventing or treating thrombosis without increasing the risk of bleeding would significantly improve the lives of LVAD patients.
Biking for Health: A Pilot Study of a Bicycling Intervention to Improve Physical Activity in Inactive Adults in an Urban Setting
PI: Rebecca Bernstein, MD, MS, Medical College of Wisconsin
Co-Investigators: Robert Schneider, PhD (University of Wisconsin—Milwaukee); Jessica Binder, BA (Wisconsin Bike Fed); Anne Dressel, PhD (University of Wisconsin—Milwaukee); Tatiana Maida, BA (Sixteenth Street Community Health Center); Jennifer Kusch, PhD (Medical College of Wisconsin)
Bicycling is a form of physical activity known to improve cardiovascular health and overall mortality. Disparities exist in prevalence of physical inactivity, cardiovascular disease incidence, and mortality between lower and higher-income communities. Members of lower-income communities are known to experience unique barriers in bicycling, one form of physical activity. The feasibility of encouraging bicycling in lower-income communities has only been explored in a few studies. This study will recruit adults from two lower-income neighborhoods in the city of Milwaukee who are very inactive and overweight or obese to be randomized to a 12-week bicycling intervention or control group. We will assess the impact of the intervention in multiple ways utilizing a mixed methods approach including geographic analysis to examine the impact of the built environment on participants’ activity levels and reported assets and barriers to bicycling. Community organizations will play roles in study design, participant recruitment and retention, and study implementation. Process outcomes including key barriers and strategies to program implementation will be critical in future efforts, including advocacy for targeted infrastructure improvements and a larger scale research study.
The Role of STAT3 in Preventing Immunosenescence in Human T and B Cells
PI: Weiguo Cui, PhD, BloodCenter of Wisconsin
Co-Investigators: Gil White, MD (Medical College of Wisconsin); Jack Gorski, PhD (BloodCenter of Wisconsin); Balaraman Kalyanaraman, PhD (Medical College of Wisconsin)
Substantial numbers of elderly are not protected by influenza vaccine, primarily due to inadequate immune responses. Therefore, improving the community health outcomes greatly depends on a better understanding of the root causes of age-associated failing of systemic immunity, known as immunosenescence. In particular, identification of biomarkers of immune aging will be extremely helpful to aid better vaccine designs tailored to the elderly. Previous work from us and others has demonstrated that STAT3 sustains the self-renewing ability of T cells. Our preliminary findings also suggest that mitochondrial STAT3 (mSTAT3) is required for the reduction of reactive oxygen species (ROS). We recently found that expression of a feedback inhibitor of mTOR, Sestrin1, was largely STAT3-dependent, which adds an additional link between STAT3 and cellular senescence. Taken together, we hypothesize that STAT3 prevents immunosenescence by regulating both transcriptional control and cellular metabolic fitness in T and B cells. This study will explore this hypothesis by first characterizing 1) STAT3 expression and activity in T and B cells from young and older (>65 year-old) PBMCs, and 2) the role of STAT3 in mitochondrial function and cellular metabolism. More importantly, we will then use the “cellular senescence signatures” generated from this study as biomarkers to predict the risk of immunosenescence among the elderly. Ultimately, knowledge gained from this study will provide mechanistic insights into vaccine designs to rejuvenate aged immune systems.
Heterobivalent PAR2 Ligands for Therapeutic Intervention in Sepsis and Inflammation
PI: Chris Dockendorff, PhD, Marquette University
Co-Investigators: Hartmut Weiler, PhD, Medical College of Wisconsin
Sepsis is the often deadly systemic inflammatory response to severe infection or trauma. It is a major contributor in more than 200,000 deaths annually in the U.S, and there is currently no approved treatment specific for sepsis. Until recently, recombinant human activated protein C (aPC) was the only available FDA approved drug for treatment of severe sepsis, but it was withdrawn from the market, in part because its beneficial effects could not be reconciled with undesired anticoagulation. aPC is a serine protease that cleaves numerous protein targets, including the Protease Activated Receptors (PARs). PARs are G-protein coupled receptors (GPCRs) that play a critical role in cell signaling, and in the context of sepsis recent results suggest that they play an important role in governing the undesired inflammatory response. We recently obtained evidence that the anti-inflammatory effects of aPC are highly correlated with the activation of specific combinations of PARs and other membrane proteins. This project aims to synthesize novel heterobivalent ligands that we have recently designed to target specific pairs of PARs and neighboring proteins, using standard organic chemistry techniques for peptide and small molecule preparation. The targets of these new compounds will be confirmed with established cell assays, and their anti-inflammatory effects will be studied and compared to aPC via gene expression profiling. The objective is to use this innovative “dual-target” approach to build highly selective and potent anti-inflammatory compounds suitable for the clinical treatment of sepsis.
A Pilot Study to Investigate Automated High-performance Software Pipelines for Analysis of Optical Coherence Tomography (OCT) Data Sets
Co-PIs: Roshan D’Souza, PhD, University of Wisconsin—Milwaukee; Jospeh Carroll, PhD, Medical College of Wisconsin; Zeyun Yu, PhD, University of Wisconsin—Milwaukee
Optical Coherence Tomography (OCT) is increasingly being used to detect and manage early stage retinal diseases such as diabetic eye, glaucoma, and age related macular degeneration. OCT allows ophthalmologists to scan the subsurface regions of the retina in order to measure thickness of various layers which in turn are key to detecting and managing pathology. The amount of data generated limits the use of manual analysis that is currently used in a clinical setting. To realize the full potential of OCT in a clinical setting requires the development of an automated software pipeline which can rapidly process data sets. In this pilot study we propose to investigate novel algorithms for noise reduction using registration, averaging and filtering, real time detection of corrupt data sets, image segmentation. To tackle the computational complexity, these algorithms will be implemented using the NVIDIA CUDA parallel computing framework in order to enable execution on latest generation graphics processing units (GPUs). Finally, the said software pipeline will be tested using real patient data sets. If successful, this project is expected to significantly advance OCT based analysis and enable preventive and maintenance procedures that are currently not possible due to the sheer amount and complexity of data processing required.
Fragment-Based Drug Discovery for Asthma, Cancer, and Vascular Disease
PI: Blake Hill, PhD, Medical College of Wisconsin
Co-Investigators: Brian Volkman, PhD, Medical College of Wisconsin; Mitchell Grayson, MD, Medical College of Wisconsin; Subramaniam Malarkannan, PhD, BloodCenter of Wisconsin; Monica Thakar, MD, Medical College of Wisconsin; Michael Widlansky, MD, MPH, Medical College of Wisconsin; Francis Peterson, PhD, Medical College of Wisconsin; Weiguo Cui, PhD, BloodCenter of Wisconsin
This project will generate a chemical library to advance the drug discovery goals of 3 independent clinician basic scientist teams focused on developing new therapeutics against asthma, cancer, and vascular disease. The library is based on chemically diverse fragments – applicable to any drug target – and will be screened against clinically validated targets using NMR to identify candidate molecules to translate into clinical use. For asthma, the target is the chemokine CCL28, for cancer, the target is disrupting the Fyn-ADAP interaction, which has been showed regulates inflammatory cytokine production from natural killer (NK) cells. By inhibiting the Fyn-ADAP with small molecules, cytotoxic NK cells could be administered to patients with minimal inflammation as a novel anti-tumor immunotherapeutic. For vascular disease, the target is the mitochondrial fission proteins Drp1 and Fis1, which has been showed are critical for endothelial dysfunction in diabetic patients. Drp1 is also implicated in cancer progression, neurodegeneration, and cardiomyopathies, which has been showed was due to impaired function. By inhibiting the Fis1/Drp1 axis, vascular dysfunction of patients would be minimized. Testing the same library with different targets will minimize false positives known to plague high throughput drug discovery efforts. Each team has the ability to produce several milligram quantities of target protein, and is poised to advance drug discovery in these clinically significant areas. The clinical co-Investigators are poised to translate lead compounds from this project to clinical studies to improve their patient’s lives.
Biomarkers of Aspiration: A Pilot Study
PI: Rahul Nanchal, MD, Medical College of Wisconsin
Co-Investigators: Nikki Johnston, Medical College of Wisconsin; Wail Mostafa Hassan, MD, University of Wisconsin—Milwaukee
Patients receiving invasive mechanical ventilation are at particular risk for Ventilator Associated Complications (VACs) which carry significant morbidity, mortality, and financial cost. Aspiration has been proposed by many as a key factor in the development and worsening of numerous VACs. However, reliable biomarkers to detect aspiration events are lacking and the current standard for diagnosing aspiration remains clinical judgment. This may lead to delay in diagnosis and potential harm from ongoing injury in the absence of institution of therapies to prevent and/or limit aspiration related events. This study will assess the sensitivity and specificity of specific biomarkers which will precisely detect the occurrence of early aspiration events in adult patients receiving invasive mechanical ventilation. We will determine both the overall incidence and relative contributions of gastric and/or oropharyngeal components to aspiration in critically ill patients receiving invasive mechanical ventilation by serially measuring gastric pepsin, salivary amylase levels and quantitatively culturing microbiota in tracheal aspirates; and correlate the proposed markers with incidence and time to VACs. Our study will confirm the incidence of aspiration in adults receiving invasive mechanical ventilation and determine the source of aspiration (gastric, oropharyngeal, or both). This study will also correlate aspiration events with incidence and time to VACs and outcomes in both populations. These data are needed before we and others can study these biomarkers across multiple institutions and test therapies to prevent aspiration and its adverse effects.
Predictive Value of Brief Personality Measures on Recovery Course and Outcome after Mild Traumatic Brain Injury (mTBI)
PI: Lindsay Nelson, PhD, Medical College of Wisconsin
Co-Investigators: James Hoelzle, PhD, Marquette University; Terri deRoon-Cassini, PhD, Medical College of Wisconsin
Mild traumatic brain injury (mTBI) is an injury with high societal cost due to its high prevalence and impact on patients’ social, emotional, and vocational functioning. A subset of individuals with mTBI experience persistent symptoms and functional impairments, and although psychological factors are thought to play major roles in the maintenance of symptoms and impairments, these factors have traditionally been crudely measured and are poorly understood. Identifying cost-efficient screening measures with prognostic value for mTBI will be critical to ensuring that patients at risk of prolonged symptoms are identified and treated early, and it will inform efforts to identify core variable sets for large-scale longitudinal studies of mTBI. This study will explore the extent to which self-report measures of personality and psychiatric symptoms, previously demonstrated to predict a variety of important health-related behaviors and outcomes, add incrementally toward the prediction of prolonged symptoms and impairments following mTBI. The study will aggregate the expertise of researchers and clinical providers from numerous disciplines involved in the assessment, treatment, and research of patients with mTBI, and it will overcome important methodological limitations in the existing literature. The data will be used to pursue extramural funding to support the launch of a larger research program within this patient population.
Adaptive Physical Recreation in Wisconsin: A Strategic Approach to Community Resources and Patient-Identified Needs
PI: Alexander Ng, PhD, Marquette University
Co-Investigators: Fang (Alice) Yan, MD, PhD, University of Wisconsin—Milwaukee; Moriah Iverson, MS, Medical College of Wisconsin; Diane Braza, MD, Medical College of Wisconsin; Kimberley Zvara, MD, Medical College of Wisconsin
This study addresses the first steps to develop a patient navigator tailored to increase physical activity among patients with disabilities through adaptive physical recreation (APR). Adults and children with disabilities face barriers to participating in APR, and we currently do not have adequate understanding of APR opportunities, resources, and what type of participation barriers our patients face. We also do not know what health outcomes are important to our patients and what tasks they would prefer an APR patient navigator to perform. This presents a critical barrier to development of an APR patient navigator. This study seeks to make strategic, patient-centered recommendations to guide development of an APR patient navigator. These recommendations will be made based on 1) a strategic assessment of APR resources and opportunities in Southeastern (SE) Wisconsin and 2) patient supplied information regarding task preferences, important health outcomes, and barriers to participation in physical activity. These recommendations will be applied in future studies to develop an APR patient navigator. Long-term, this work will significantly impact clinical care for this population by improving health outcomes and quality of life through physical activity.
Qualitative Assessment of Pilot Mental Health Court Intervention in Milwaukee County
PI: Michael Oldani, PhD, University of Wisconsin—Whitewater
Co-Investigators: Paul Brodwin, MA, PhD, University of Wisconsin—Milwaukee; Carol Tsao, MD, JD Medical College of Wisconsin; Paige Styler, JD, Office of the State Public Defender
Jails and prisons are now the country’s largest de facto treatment providers for criminal offenders with mental illness. In March of 2014 the Public Defender’s Office, the Office of the District Attorney and Judge J. Kremers created Milwaukee County’s first pilot Mental Health Court (MHC) and Coordination Care Team (CCT) to help mentally ill offenders with minor criminal offenses. The goal of the MHC and CCT is to structure care and supervision in order for offenders to receive probation through the Department of Corrections (DOC) and appropriate psychiatric treatment. During the formation of the MHC/CCT the PI was consulted and a long-term qualitative study was proposed and agreed upon that would work to assess and develop a set of best practices for the MHC/CCT. This study will be a one-year qualitative documentation and assessment of the daily operations of the MHC, CCT meetings, and the evolving relationships between the MHC, the CCT, and 5 mentally ill offenders. The central aim is to identify a set of best practices that will ensure the long-term viability of the court and help to establish permanent status in Milwaukee County. Specific attention will be paid to how the MHC has placed offenders into a new avenues of psychiatric care and legal supervision. A grounded theory approach will be employed to identify new categories, concepts, and practices that best serve the offenders, the MHC and CCT members now and in the future.
Toward a Bioinformatics and Bioengineering Core for Southeastern Wisconsin
PI: Lars Olson, PhD, Marquette University
Co-Investigators: Elizabeth Worthey, PhD, Medical College of Wisconsin; Matthew Anderson, MD, PhD, BloodCenter of Wisconsin; Serdar Bozdag, PhD, Marquette University, Valerie Trapp-Stamborski, PhD, BloodCenter of Wisconsin
The Human Genome Project led to the development of new genomic analysis technologies, which in turn has led to several significant medical breakthroughs. As our ability to interrogate the genome improves, we will be better able to diagnose and monitor disease. One limiting factor is the ability to accurately analyze the data produced, as is evident by the number of CTSI investigators who need bioinformatic resources. Expertise in the area of bioinformatics is in short supply among CTSI partners and recruiting new talent has proven difficult. The degree of resources needed varies between (1) long term collaborators and bioinformatics expertise, (2) short-term talent to complete a specific task or analysis, and (3) bioinformatics tools for analysis of data. One solution would be a CTSI bioinformatics/bioengineering core that can provide support for investigators with changing needs and retain talent in southeast Wisconsin. Our study will develop and assess two projects at CTSI partner institutions. We will target specific areas of analytical need and serve as a template to develop future talent. Since genomic regions sharing high levels of sequence identity provide a challenge for existing NGS alignment algorithms and often result in mapping errors, this study will design an algorithm suitable for re-alignment of reads with high sequence identity. Additionally, we will design an algorithm that uses a training data set to allow for detection of low frequency variants.
Measuring Energy Expenditure in Children with Spina Bifida and Down Syndrome: A Feasibility Study
PI: Michele Polfuss, PhD, RN, CPNP-AC/PC University of Wisconsin—Milwaukee
Co-Investigators: Kimberley Zvara, MD, Medical College of Wisconsin; Paula Papanek, MS, PhD, M.P.T, ATCL, FACSM, Marquette University; Kathleen Sawin, PhD, CPNP-PC, FAAN, University of Wisconsin—Milwaukee
Childhood obesity is a public health crisis, with an increased prevalence in the special needs population. Accurate measurement of energy expenditure (EE) is a crucial construct in weight management. Methods to measure EE have been understudied in the special needs (SN) population and even less in children who rely on wheelchairs as their primary means of ambulation. This creates a barrier to adequate treatment or prevention of obesity in this high-risk population. This study is based on the Individual and Family Self-Management Theory. The objectives of the proposed feasibility study are to: 1) Determine feasibility of implementing the protocol’s subjective and objective measures. 2) Determine best placement of accelerometers (waist vs. wrist) based on convenience, feasibility of wearing, and accuracy as compared to the criterion of Doubly Labeled Water (DLW). 3) Determine the likelihood of obtaining two different measures of DLW (saliva and urine) and assess the variation between each method. 4) Identify willingness of parents and children to complete journaling of physical activity as well as assess accuracy of journaling as compared to criterion of DLW. Findings will provide information integral to understanding a crucial construct of weight management in the SN population by evaluating various methods of measuring EE in children with spina bifida, a physical disability, and children with Down syndrome, an intellectual disability
Advancement in Diagnosis and Treatment of Granulomatous/lymphocytic Interstitial Lung Disease
PI: John Routes, MD, Medical College of Wisconsin
Co-Investigators: Brian Hoffmann, PhD, Medical College of Wisconsin; Andrew Greene, PhD, Medical College of Wisconsin; Roshan D’Souza, PhD, University of Wisconsin—Milwaukee
Common variable immunodeficiency (CVID) comprises the most clinically important primary immunodeficiency due to its prevalence, serious complications and long-term costs of therapy. Granulomatous/lymphocytic interstitial lung disease (GLILD) occurs in 10-15% of patients with CVID. The causes of GLILD are unknown and there is no established standard of care for the treatment of GLILD. We recently found that immunosuppressive therapy using rituximab (RTX), a monoclonal antibody against the B cell antigen CD20, and an anti-metabolite, azathioprine (AZA), improved the pulmonary function and radiographic abnormalities seen on high resolution CT (HRCT) scans of the chest in select cohort of patients with GLILD. Based on previous studies we hypothesize that: 1) Specific cellular pathways are dysregulated in DR+ T cells and contribute to the pathogenic inflammatory state in the lung; 2) Specific cytokine receptors will be upregulated in DR+ T cells compared to DR- T cells and contribute to homing to the lung. This study seeks to identify the mechanisms behind the pathogenesis in a subset of GLILD patients and suggest potential novel therapies to normalize dysregulated cellular pathways leading to this disease.
Sensorimotor Integration and Aging: Effects of Reduced Sensory Acuity and Cognitive Capability on Coordinated Control of Limb Position
PI: Aaron Suminski, PhD, Marquette University
Co-Investigators: Edgar DeYoe. PhD, Medical College of Wisconsin; Robert Scheidt, PhD, Marquette University; Kristy Nielson, PhD, Marquette University
While some individuals maintain high levels of motor coordination and cognitive performance into advanced age, aging is commonly related with declines in sensory information processing and ability to plan, organize, and switch between competing tasks. These declines often become most conspicuous in situations wherein individuals are required to divide attention between multiple simultaneous tasks (e.g. turning a corner and avoiding pedestrians while driving a car). In this project we propose to investigate the how age related declines in sensorimotor and executive functions impact the performance of – and local brain activation elicited by a task requiring the stabilization of limb position. Four groups of seniors (65 years of age or older) participate in this functional MR imaging study. They will be divided based on their performance on a battery of tests evaluating their somatosensory acuity and executive function. Two groups will contain subjects with either nominal or low sensory acuity, while the remaining groups will contain subjects with either nominal or low executive function. We hypothesize that age-related declines in sensory feedback processing and executive control will result in quantifiable deficits in the control of arm stability and differentially impact the neural circuits involved in the stabilization of the arm. Such knowledge will be valuable clinically to optimize training strategies to combat the effects of aging on sensorimotor integration and control and may ultimately result in a simple testing strategy to evaluate the ability of seniors to drive and live independently.
Pharmacogenetic Analysis of Nicotine Metabolizing Enzymes in Sudden Infant Death Syndrome (SIDS)
PI: Tara Sander, PhD, Medical College of Wisconsin
Co-Investigators: Julie Tetzlaff, PhD, Medical College of Wisconsin; Emmanuel Ngui, DrPH, University of Wisconsin- Milwaukee; Wieslawa Tlomak, MD, Medical Examiner’s Office; Ray Hoffmann, PhD, Medical College of Wisconsin
SIDS is the unexplained death of an infant within one year of life that cannot be explained after autopsy case investigation. Most deaths are African-Americans (AA), who are 4 times more likely to die, making it one of the worst racial disparities. Cigarette smoking is the number one SIDS risk factor, after supine sleeping position. An infant exposed to cigarette smoke must metabolize nicotine to its inactive metabolites to minimize adverse health effects. Infants exposed to cigarette smoke are at greater risk for SIDS, in part because the toxic compounds alter brain activity and interfere with regulation of the infants’ breathing. Importantly, races and ethnicities differ in their ability to metabolize nicotine effectively and efficiently. In particular, it has been demonstrated that AAs are often poor metabolizers of nicotine, in part, due to single nucleotide polymorphisms in enzymes that metabolize nicotine such as FMO3, CYP2A6 and CYP2B6. In alignment with the well accepted SIDS triple risk model, we propose that if a baby, is (1) exposed to nicotine via cigarette smoke, (2) has a reduced ability to metabolize nicotine, and (3) is within a critical age range (< 1 year old), then the child is more likely to succumb to SIDS . We propose to develop a clinically diagnostic pharmacogenetics panel to detect genetic variants associated with nicotine metabolism. We will determine if AA SIDS victims from smoking environments are more likely to have genetic errors in nicotine metabolizing enzymes, compared to AA SIDS victims from non-smoking environments.
Near-Infrared Photobiomodulation for the Treatment of Diabetic Macular Edema
PI: Sandeep Gopalakrishnan, MS, PhD, University of Wisconsin—Milwaukee
Co-Investigators: Judy Kim, MD, Medical College of Wisconsin; Joseph Carroll, PhD, Medical College of Wisconsin; Thomas Connor, MD, Medical College of Wisconsin; Kimberly Stepien, MD, Medical College of Wisconsin; Janis Eells, MS, PhD, University of Wisconsin—Milwaukee
Diabetic retinopathy is the most common complication of diabetes mellitus and a leading cause of preventable blindness. Diabetic macular edema (DME) is a common retinal manifestation of diabetic retinopathy. Photobiomodulation (PBM) by light in the far-red to near infrared (NIR) range of the spectrum (600-900 nm) has been shown to be a non-invasive and effective treatment modality for wound healing and soft-tissue injury and recent studies have demonstrated the efficacy and therapeutic potential of NIR-PBM in experimental and clinical retinal disease. The long-term objective of our studies is to develop PBM as a stand-alone or adjunct therapy for the treatment of diabetic retinopathy and other retinal diseases. The objective of this proposal is to test the hypothesis that NIR-PBM will decrease retinal inflammation, reduce oxidative stress, attenuate the severity of diabetic macular edema and thus improve visual acuity in patients with DME. This translational research project will bridge recent, promising basic research on the effects of PBM on cellular function with a clinical treatment for a significant medical problem, diabetic macular edema. We have assembled an exceptionally qualified and diverse team of investigators from the University of Wisconsin- Milwaukee and the Medical College of Wisconsin with combined expertise in photobiomodulation, ophthalmology and retinal imaging. We will recruit patients with DME and evaluate the safety and efficacy of PBM in order to determine the utility of this cost-effective, innovative, and non-invasive therapeutic approach with the end goal of reducing health care costs and improving quality of life.