CCTS Pilot Grant Projects Funded
2008 Pilot Grant Projects Funded
February 3, 2009
The UIC Center for Clinical and Translational Science (CCTS) announced this week that it has awarded funding to seven projects in its 2008 Pilot Grant Program. The program, supported by the Office of the Provost, the Office of the Vice Chancellor for Research, and the Health Science Colleges, focuses on clinical and translational research – research that involves human subjects, facilitates human subject investigations, establishes infrastructure related to human subject investigation, or concerns disease mechanisms with clear, near term implications for therapeutics or prevention. Seventy-five proposals were received from a variety of UIC departments and colleges, representing the Chicago, Peoria and Rockford campuses. The funded projects include investigators from 17 different departments and 4 colleges.
We are pleased to announce the following Pilot Grant awards:
“Mast Cell, Macrophage, and Eosinophil Interactions in Asthma”
PI: Steven J. Ackerman, Ph.D., Professor, Department of Biochemistry and Molecular Genetics, College of Medicine; Co-Investigators: John Christman, M.D., Professor, Pulmonary, Critical Care and Sleep Medicine, College of Medicine; Richard Ye, Ph.D. Professor, Pharmacology, College of Medicine; H. Ari Jaffe, Associate Professor, Pulmonary, Critical Care and Sleep Medicine, College of Medicine.
The purpose of this CCTS Preliminary Studies Pilot Grant is to establish interdisciplinary collaborations among the 3 participating investigators, all tenured professors in clinical and basic departments at UIC, in the area of asthma and allergy research. The 3 investigators and their laboratories have been interacting since 2006 in developing a collaborative research program aimed at obtaining NIH/NIAID funding for an Asthma and Allergic Diseases Cooperative Research Center (AADCRC) at UIC, for which the first application (1U19 AI077500-01, Steven J. Ackerman, PI) in response to RFA-AI-07-002 was already submitted to the NIAID in May 2007. This program will utilize the expertise of the investigators, Drs. Ackerman, Christman and Ye, in studies of eosinophils, mast cells and macrophages and their roles in asthma and allergic diseases pathogenesis. A key part of this clinical/translational research program is obtaining clinical samples from asthmatic patients for studies designed to understand the cellular basis and mechanisms of allergic pulmonary inflammation, tissue damage and airways remodeling in asthma. The CCTS Preliminary Study Grant is critical for providing the seed funding needed for our group to develop the clinical cores of this AADCRC, and to begin using CCTS core resources for patient recruitment, and obtaining peripheral blood, BAL fluid and inflammatory cells from the lung before and after subsegmental allergen challenge-induced late-phase reactions, specifically through the use of an investigative bronchoscopy and subsegmental bronchoprovocation with allergen clinical core (Core A) and inflammatory cell purification core (Core B). These clinical/translational cores and procedures will enable us to effectively address the summary statement critiques of our proposed AADCRC in terms of providing evidence of feasibility, experience and institutional support at UIC, so that we can build a more solid and fundable AADCRC application based on sound preliminary clinical studies using these clinical cores and samples.
“T-cell Immunotherapy for Adenoviral Infections of Hematopoietic Stem Cell Transplant Patients”
PI: Marlene Bouvier, Ph.D., Associate Professor, Microbiology and Immunology, College of Medicine; Co-Investigator: James L. Cook, M.D., Professor, Infectious Diseases, College of Medicine.
Adenovirus (Ad) infections cause morbidity and mortality in haematopoietic stem cell transplant patients. Antiviral drugs are ineffective and toxic. The linkage between T-cell-specific immune reconstitution and recovery from Ad infection has lead to initial success with adoptive cytotoxic T-cell (CTL) therapy to treat these Ad infections. However, further understanding of the mechanism underlying cellular immune responses to Ad is needed to optimize CTL immunotherapy. Our studies have characterized the mechanism by which the Ad E3-19K protein suppresses class I MHC antigen expression - an immunomodulatory effect that reduces CTL efficacy. We propose further studies of E3-19K/class I interactions at the molecular and cellular levels to improve strategies for CTL and patient selection for adoptive, antiviral CTL immunotherapy. We have established collaborations with colleagues from the Baylor College of Medicine that will provide haplotype information, human CTL lines, target cells, and clinical outcomes data to test the correlation between the E3-19K effect on class I expression and the efficacy of adoptive CTL immunotherapy. Findings from these studies will form the basis of a proposal to support long-term studies of E3-19K/class I effects that can improve the rationale and strategies for development of effective, antiviral CTL immunotherapy.
“Three Dimensional Human Ovary Organ Culture to Study Early Ovarian Cancer Events”
PI: Joanna E. Burdette, Ph.D., Assistant Professor, Medicinal Chemistry and Pharmacognosy, College of Pharmacy; Co-Investigator: Nita K. Lee, M.D., Obstetrics and Gynecology, College of Medicine.
The primary objective of this proposal is to discover whether human ovarian surface epithelium (OSE) can be grown in a three-dimensional alginate system. OSE are the progenitor cells for over 90% of all ovarian cancers. OSE cells grown under existing 2- D conditions change shape and die making studies into the events that change a normal cell into a cancer cell extremely limited. The long-term benefit of generating such a system is that it would allow for future studies aimed at identifying events that transform ovarian cells into cancer.
“Planning Grant for Developing Research in Rural Cancer Control”
PI: Michael L. Glasser, Ph.D., Associate Dean for Rural Health Professions, University of Illinois at Rockford; Co-Investigators: Usha Menon, Ph.D., Associate Professor, Biobehavioral Health Science, College of Nursing; Lissette Piedra, Ph.D., Assistant Professor, Social Work, UIUC.
We propose a one-year planning project to develop an R21 proposal addressing cancer screening and treatment among rural residents. The navigator model will be adapted from current successful research in cancer screening for urban communities. Navigation has been shown to be especially successful in reducing health disparities. The project in this planning grant will implement and evaluate navigator roles in relation to cancer education/intervention in rural communities. An important aspect is development of an interdisciplinary team with participation from medicine, medical sociology, nursing, social work, and public health. The project brings together research expertise from three campuses: University of Illinois at Chicago; University of Illinois at Urbana-Champaign; University of Illinois at Rockford.
“Novel Electroretinographic Mapping of Retinal Function for Diagnosis of Progressive Eye Disease”
PI: John R. Hetling, Ph.D., Associate Professor, Bioengineering, College of Engineering; Co-Investigator: Janet Szlyk, Ph.D., Professor, Ophthalmology and Visual Sciences, College of Medicine.
“Activation of P21 Activated Kinase-1 as a Novel Therapeutic Strategy for Ischemic Heart Diseases”
PI: Yunbo Ke, Ph.D., Research Assistant Professor, Physiology and Biophysics, College of Medicine; Co-PI: R. John Solaro, Ph.D., Professor, Physiology and Biophysics, College of Medicine; Co-Investigator: Samuel C. Dudley, M.D., Ph.D., Professor, Cardiology, College of Medicine.
Ischemic heart diseases (reduced blood flow to heart muscle) affect 16 million people and result in about 450,000 deaths each year in the United States. Angina (manifested as chest pain) and myocardial infarction (heart attack) are consequence of the diseases caused by flawed coronary circulation. An ischemic heart becomes more sensitive and fragile to stress imposed by demanding physical activity and emotional disturbances, which demand that a functionally compromised heart to work harder. The signal to work harder comes as blood and nervous system signals called β-adrenergic signals.
We have discovered a novel signaling pathway that shields heart muscle cells against the call of these signals. The protection is mediated by p21 activated kinase-1 (Pak1), an enzyme that blocks the effects of the β-adrenergic stimulation during ischemia.
Being a key signaling molecule in the heart, Pak1 activity can be turned on by a group of structurally-related small molecules (drugs). Some of the compounds are even under clinical trials as drug candidates for other diseases, which indicate that Pak1 has high “drugability”. Our objective is to identify the molecular mechanism whereby Pak1 is turned on and off by these compounds.
Our major goal is to develop novel therapeutics for ischemic and other major cardiac diseases, which are more selective and competent than β-adrenergic blockers currently in use.
“A Pilot Study of White Matter Involvement in Glioma Patients Using High-Resolution Diffusion MRI”
PI: Xiaohong Joe Zhou, Ph.D., Associate Professor, Neurological Surgery, College of Medicine; Co-Investigators: Herbert H. Engelhard, M.D., Ph.D., Associate Professor, Neurological Surgery; John L. Villano, M.D., Ph.D., Assistant Professor, Oncology, College of Medicine; Tibor Valyi-Nagy, M.D., Ph.D., Associate Professor, Pathology, College of Medicine.
Malignant glioma is one of the most lethal tumors. Despite surgical resection, radiation and chemotherapy, the prognosis remains poor due to the high rate of local recurrence. This indicates that significant amount of viable tumor cells remain in some sites following therapy. It is known that white-matter fiber tracts are common sites for harboring tumor cells. Identifying these sites is a critical step to prevent, or at least slow, the gross recurrence, leading to improved clinical outcome. The central hypothesis of the proposed research is that the presence of tumor cells in white-matter fiber tracts can be detected by diffusion tensor magnetic resonance imaging (DT-MRI) using a new imaging marker, known as regional fiber coherence index (r-FCI). The overall objective of this proposal is to demonstrate the feasibility of using r-FCI for identifying white-matter fiber tracts substantially invaded by tumor in areas that are relevant to local recurrence. This new marker is expected to provide higher sensitivity and better specificity than existing imaging markers. The project has three specific aims. First, a high-resolution (i.e., 0.9x0.9x3 mm3) DT-MRI technique will be developed at 3 Tesla to acquire diffusion images of the human brain with adequate signal-to-noise ratio (>20) and within clinically acceptable times (i.e., ~10 minutes). The high-resolution imaging technique will allow r-FCI to be quantified reliably. Second, we will evaluate the sensitivity, specificity and diagnostic accuracy of r-FCI for identifying white-matter fiber tracts invaded by tumor. This will be accomplished by comparing r-FCI values with histopathology results of biopsies taken from eight patients with malignant gliomas. Finally, we will demonstrate that r-FCI offers a significant advantage over fractional anisotropy (FA) and mean diffusivity (MD) in delineating white-matter fiber tracts substantially infiltrated by tumor in the presence of vasogenic edema. The proposed project will be accomplished by an interdisciplinary team with complementary expertise spanning from imaging physics to neurosurgery, neurooncology, pathology, and biostatistics. To ensure coordinated effort and facilitate interaction among the investigators, we will have a bi-weekly meeting to review the progress of the project, discuss the emerging issues, and prepare for an NIH R01 application. Successful completion of the project will equip us with a new tool to translate an advanced imaging technique to improving patient care by preventing or significantly slowing glioma recurrence. Moreover, this pilot study also provides a vehicle to bring together a team of UIC researchers with diverse expertise to carry out an interdisciplinary translational research project that will lead to extramural funding from the NIH.