Pilot Projects in Clinical and Translational Science
Congratulations to the Winter 2017 CCTS Pilot Grant Awardees:
Olusola Ajilore, MD, PhD, Associate Professor, Department of Psychiatry, UIC College of Medicine
Co-Investigators: Alex Leow and Philip Yu
Capture And Modulation of Emotion Regulation Inferred from Connectivity Analysis
The goal of the proposed project is to use brain network connectivity patterns to determine the best way to stimulate the brain in order to help people regulate their emotions. Emotion regulation (ER) has been shown to be impaired in mood and anxiety disorders and impaired ER may increase the risk of relapse in patients who have recovered. Enhancing ER would have a tremendous impact in getting patients well and keeping them well. One promising new method for enhancing ER is transcranial current stimulation (tCS). We propose to use tCS in mood and anxiety disorder patients to enhance ER.
Amy Christison, MD, Assistant Professor, Department of Pediatrics, University of Illinois College of Medicine- Peoria
Co-Investigators: Peter Gyarmati and Yajing Song
Composition and Collection Feasibility of Gut Microbiota in Children with and without Obesity
Adults with obesity have an imbalance of bacteria in their intestines which may contribute to weight gain and diseases related to obesity. Restoring the balance of these bacteria (the “microbiota”) could help reduce weight and related diseases. However, little is known about this imbalance in children with obesity. This research study will map out the compositions of the gut microbiota of children and compare them with those of children who have healthy weights and different degrees of obesity. We will also measure the amounts of fatty acids in the stools which are an indication of how efficiently the intestines absorb calories from food. If an imbalance is detected in children with obesity, then this information can help researchers test ways to restore the gut microbiota with hopes of reducing weight and some of its related health problems.
Lyndon Cooper, DDS, PhD, Associate Dean for Research, Head of the Department of Oral Biology, UIC College of Dentistry
Co-Investigators: Timothy Koh and Ghadeer Thalji
Monocyte/Macrophage Control of Induced Bone Repair
Bone formation is controlled by both local bone factors and systematic health factors. In cases where bone healing does not occur and local factors have been controlled, systematic factors are likely acting to prevent proper healing. The immune system works generally throughout the body and can superimpose its actions at local sites such as at bone fractures. In this study, we will directly evaluation the role of immune system cells that control healing- monocytes- on the process of bone repair. We will perform two experiments. One will examine the cellular activities in bone healing when monocytes are present versus when they are absent. This will inform us regarding the role of monocytes in bone healing. The second experiment will explore what happens when monocyte function is disturbed. A good example of this is the common disease diabetes. Here, we will investigate how monocytes from diabetic mice influence the process of bone healing compared to monocytes from healthy mice. In this way, we may learn how systematic diseases influence bone healing by way of the immune system and monocytes. What we learn here may be used to improve bone healing in individuals with systematic diseases like rheumatoid arthritis and diabetes.
Dennis Grayson, PhD, Professor of Molecular Neuroscience, Department of Psychiatry, UIC College of Medicine
Co-Investigators: Alessandro Guidotti, and Alan Kozikowski
Better DNA methyltransferase (DNMT) inhibitors to correct the behavioral and molecular endophentoypes of an animal model of psychosis
More than one percent of the population suffers from schizophrenia (SZ) and bipolar (BP) disorder. Patients suffer from hallucinations, delusions, and cognitive deficits. Available therapies, which are only partially effective, have not improved markedly in the last 25 years. Large numbers of genes are dysregulated in post-mortem human brain of SZ subjects. There are also overlapping but distinct sets of genes dysregulated in peripheral blood leukocytes in SZ patients as well. We have studied the epigenetic profiles of genes implicated in SZ and BP disorder and would like to develop new drugs to treat these devastating disorders. The field of epigenetics refers to mechanisms by which cells and neurons mediate changes in gene expression in response to environmental signals. For example, trauma or physical abuse during early life will impact brain function in the adult. Infections during pregnancy will impact neurodevelopment in newborns as another example. The interaction of the environment on the genome impacts not only neurodevelopment but cognition, sensory perception, and emotion in later life. Some environmental factors mediate changes in DNA methylation at specific genes critical for brain function. We propose a comprehensive plan to test compounds using in vitro and in vivo preclinical methods to examine their ability to reverse the abnormalities observed in a prenatal stress model of SZ and BP disorder in the mouse. If these compounds are successful in correcting the behavioral and biochemical abnormalities typical of the pre-natal stress mouse, we will consider using developing these compounds for use in human clinical trials.
Jan Kitajewski, PhD, Professor and Head, Department of Physiology and Biophysics, UIC College of Medicine
Co-Investigators: Kent Hoskins and Arakadiusz Dudek
Jagged1 as a Therapeutic for Breast Cancer in Diverse Patient Populations
This proposal seeks to test a new potential therapy that targets aggressive breast cancers and to see if this therapy would help alleviate racial health disparities. African-American and Hispanic breast cancer patients have worse clinical outcomes than Caucasian patients. We predict this is caused by a protein called Jagged1, as high Jag1 levels in breast cancer samples correlates with poor outcomes for these patients. The currently available Jag1-Notch inhibitors have limited clinical application due to serious gastrointestinal toxicity. We have developed a new therapeutic protein which blocks the activity of Jagged1 with fewer side effects than current similar treatments. We will further test this therapy to establish if it is safe and effective. We will also evaluate Jag1 expression in breast cancer samples from a large diverse patient set (including African-American, Hispanic, and Caucasian women) to determine if differences in Jag1 levels predict poor outcomes. Our goal is to define the populations that would benefit most from Jag1 inhibition therapy and prepare for clinical use of this inhibitor. If successful, it will reduce racial/ethnic differences in breast cancer outcomes and improve overall patient outcomes.
Orly Lazarov, PhD, Professor, Department of Anatomy and Cell Biology, UIC College of Medicine
Co-Investigators: Richard Minshall, Laura Pedelty, Jacob Haus and Marcelo Bonini
Mechanisms of cognitive deterioration in Type 2 diabetes
Increasing evidence suggests people with diabetes, especially type 2 diabetes (T2DM), are at higher risk of developing Alzheimer's dementia. Many people with diabetes have brain changes that are hallmarks of Alzheimer's disease. Cognitive impairments are a harsh decree for T2DM, they are not able to perform not even simple daily life activities by themselves, nor remember their relatives and friends. The mechanism by which T2DM patients develop Alzheimer’s disease is not known. In addition, there are no tools to predict the development of Alzheimer’s disease. This project poses to develop a novel biomarker for the diagnosis of Alzheimer’s disease in T2DM patients. In addition, the project unravels molecular signals that may cause T2DM patients to develop Alzheimer’s disease. Thus, funding this research will be fundamentally crucial for the improvement of human health. If successful, this study will lead to significant breakthroughs that will prevent T2DM-induced Alzheimer’s disease.
Laurie Quinn, PhD, RN, Professor, Department of Biobehavioral Health Science, UIC College of Nursing
Co-Investigators: Joan Briller, Bilgay Balserak, Ulf Bronas, Eileen Collins, Cynthia Fritschi, Chang Park
Gestational Diabetes Mellitus: Influencing Metabolic and Cardiovascular Outcomes Through Physical Activity
The proposed research study “Mother-Infant, Music-Enhanced, Cadence-based hOme-based rhythm-controlled Exercise” program will improve human health in the near and distant future by improving the physical activity level and therefore health of women and babies at risk for developing diabetes. Chicago and neighborhoods near UIC are particularly in need because of the number of people that either have diabetes or are at risk for developing diabetes. Taking advantage of the natural bond between mother and child and the common activity of taking the baby out in a stroller allows the proposed research to fit seamlessly into the mothers' daily lives and addresses barriers to previous DM physical activity studies.