Congratulations to our 2009 Pilot Project Awardees!
Brian K. Bonish, MD, PhD
Daniel Gentry, PhD
Amanda L. Marzo, PhD
Najia Shakoor, MD
Title: Role of Toll Like Receptors in Directing T-cell Responses in Human Skin
Title: Chicago Health Surveillance System Pilot
PI: Brian K. Bonish, MD, PhD. Assistant Professor, Dermatology and Immunology/Microbiology
Abstract: Psoriasis is a common chronic skin disease affecting 1-3% of the United States population. Unfortunately, despite recent advances in treatment, the underlying pathologic mechanism of psoriasis remains unknown. However, it is well known flares of psoriasis can be triggered by bacterial infections, and that plaques can be initiated by trauma to the skin, potentially exposing normally protected areas to bacterial antigens. In addition, psoriasis can be triggered by a topical medication that activates Toll-Like receptor (TLR7).
TLRs are components of the immune system that can react to unique bacterial and viral molecules. Activation of TLRs have been linked to psoriasis, but the overall activity and function of these receptors in the skin is poorly understood. In order to better understand the roll of TLRs in psoriasis, these studies will examine their function in normal human skin by examining the production of inflammatory molecules and types of T-cells produced when TLRs are triggered in skin. This information will be useful for understanding both the normal immune response in skin as well as the pathologic response in psoriasis, with the ultimate goal of developing more specific treatments for psoriasis.
PI: Daniel Gentry, PhD, MHA, Professor, Department of Health Systems Management
Co-PIs: Martha Clare Morris, ScD, MS, Professor, Department of Preventive Medicine Bala Hota, MD, MPH, Assistant Professor, Department of Internal Medicine Briana Jegier, PhD, MS, Assistant Professor, Department of Women, Children and Family Nursing Raj Behal, MD, MPH, Assistant Professor, Department of Internal Medicine
Abstract: This study is designed to develop and test a pilot system that will eventually lead to a Chicago city-wide health surveillance system that will provide comprehensive health behavior and health status data. Health disparities in Chicago reflect the national picture in the United States. Addressing these disparities is both a national and a regional priority. More comprehensive region-wide information is required to assess the prevalence of unhealthy behaviors and their associated disease burden, to carefully plan interventions that are targeted to populations and communities, and to monitor progress in health behavior change and improvements in health status over time.
This project builds on previous work by both individual researchers across Chicago and existing collaborations between academic medical centers, the U.S. Department of Health and Human Services, the Chicago Department of Public Health, the Cook County Health Department, and the American Medical Association. This work is closely tied to the efforts of Building a Healthier Chicago (BHC).
Title: Mechanisms by Which IFN-A Enhance Anti-Tumor Responses
PI: Amanda L Marzo, Assistant Professor, Department of Immunology/Microbiology
Abstract: A neglected area in tumor immunity is the problem of effector cell access to the tumor site. We know that tumor growth is usually associated with poor lymphocytic infiltration and there are several studies that support the idea that the vasculature is a barrier to immune cells. Our own studies have shown that tumor-specific CD8+ T cells are unable to infiltrate the tumor despite being activated by antigen in the draining lymph nodes. Something is acting as a barrier at the tumor site preventing CD8+ T cells from entering. The breakdown of this barrier is associated with CD4+ T cell infiltration and the upregulation of MHC Class II and the intercellular adhesion molecule ICAM-1.Type I interferon's (IFN) are a family of cytokines with potent activities including the ability to u-regulate various adhesion molecules including L -selectin and ICAM-1. These molecules are associated with T cell trafficking and endothelial interactions. Therefore, our specific aim is to determine the effects IFN-a therapy has on the tumor microenvironment. To address this aim we will determine whether IFN-a therapy upregulates molecules, such as the cell-cell interactions molecule ICAM-1, which in turn aids in the induction of lymphocytic infiltrates at the tumor site and thus facilitates tumor eradication. These studies will provide insight into the mechanisms by which IFN enhance anti-tumor responses.
Title: The Effects of Specialized Footwear in Osteoarthritis (OA) of the Knee
PI: Najia Shakoor MD, Section of Rheumatology
Abstract: Osteoarthritis (OA) is the most common arthritic condition in the U.S. In OA of the knee, increased medial joint loads are associated with radiographic severity, disease progression, and pain, whereas reducing loading of the medial compartment appears to have symptomatic benefits. The lower extremity acts as a single kinetic chain, and alterations at one level may have a profound impact on the other levels; hence, one strategy to reduce loading at the OA knee is to alter mechanics at the foot. Yet shoes have conventionally been engineered to focus on foot comfort, and little attention has been paid to the effects they may have on loads in the more proximal joints. Taking into account the loading dynamics of the foot, we have designed a "mobility" shoe that incorporates unique biomechanical characteristics to reduce joint loads at the knee during ambulation. The conceptual design for the shoe was based on our observation that conventional modern walking shoes result in a nearly 14% increase in dynamic knee loads in subjects with knee OA compared to barefoot walking in the same individuals.Our preliminary data also suggest that use of the "mobility shoe" is associated with a 46% reduction in pain and 17% reduction in knee loads from baseline over 6 months.
This pilot project's aim is to further evaluate the therapeutic utility of the "mobility" shoe in OA of the knee. Since the mobility shoe's primary advantage is hypothesized to be related to its sole flexibility, in this project the "mobility" shoe will be compared to a less flexible control shoe. This pilot study will aim to establish the tolerability of both these shoes for evaluation in a larger double-blind randomized control trial in subjects with OA and to attest to the clinical and biomechanical benefits of shoe flexibility for knee OA. The study's overall hypothesis that the use of the "mobility" shoe will result in significant reductions in knee loads and pain compared to a control shoe in subjects with symptomatic knee OA, and that these reductions will be durable over time. This study will randomize 20 subjects with symptomatic OA of the knees into two groups, one that will receive the mobility shoe and a second that will receive a control walking shoe. Subjects will undergo a baseline radiographic evaluation, clinical evaluation for pain, and gait evaluation for measurement of dynamic joint loads. They will wear the study shoes for at least six hours a day, six days a week, and then follow up at 6 weeks, 12 weeks and 6 months for repeat clinical evaluation and gait analyses. Primary data analyses will focus on changes in joint loads and pain at the lower extremity joints, with the "mobility" shoes compared to the "control" shoes. This is a novel investigation in that footwear has not been sufficiently examined or designed for "joint protection". It is an important proposal, because it could potentially have enormous impact on the design of footwear. Furthermore, if proven successful, it could provide a practical, relatively inexpensive, and "disease-modifying" interventional approach to the treatment of knee OA.