The ultimate goal of the Clinical & Translational Science Collaborative in Cleveland, directed by Pamela B. Davis, M.D., Ph.D. and Richard A. Rudick, M.D., is to provide complete service and integrated clinical translational research capability within the Cleveland community that will improve the health of patients in Northeast Ohio through patient-based research.
As a reminder, the CTSC must receive acknowledgement on relevant publications. Please include the following text: "This publication was made possible by the Case Western Reserve University/Cleveland Clinic CTSA Grant Number UL1 RR024989 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health and NIH roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH."
The Case Proteomics Center in HIV/AIDS & Drug Abuse is designed to apply state-of-the art proteomics and systems biology tools to investigate HIV pathogenesis in the context of drug abuse and provide significant biomarkers of HIV infection, co-infection with other viruses, and drug abuse. During the pilot phase, we will undertake three inter-related projects designed to provide a better understanding of the impact on immune function and activity in HIV-infected individuals who are also exposed to addictive drugs, and the important viral co-factor Hepatitis C (HCV). In each of these projects there will be a direct examination of the proteomic responses in epithelial or T-cells and parallel examination of plasma readouts from affected patients. A major outcome of these projects will be development of informative biomarkers and methods that can be used in large-scale population studies to further evaluate the impact of drug use on HIV disease. The Center is directed by Dr. Mark Chance, Director of the Case Center for Proteomics, and an internationally recognized expert in proteomics and system biology in collaboration with Dr. Jonathan Karn, Chair of the Department of Molecular Biology & Microbiology and Co-Director of the Case Center for AIDS Research (CFAR), and an expert in HIV/AIDS molecular biology. The pilot projects are the work of a strong pre-existing multi-disciplinary team at Case that combines significant biological expertise in HIV/AIDS within the Department of Medicine, the Department of Molecular Biology & Microbiology, the Department of Biological Sciences (Dental School) and CFAR. These investigators have already assembled significant molecular biology and proteomics data to provide testable hypotheses within the context of three Pilot Projects served by a Proteomics and Bioinformatics Core. The three projects, with the cooperation of the clinical core of the Case CFAR, will recruit appropriate patient cohorts to provide relevant samples. The proteomics team in the Core will then conduct proteome expression analysis of cases versus relevant control populations, with statistically significant targets provided to the Bioinformatics team. This team will not only provide network analysis and pathway identification within the context of the biological questions to be addressed, but will correlate the proteomics pathway models with known pathways of drug addiction and HIV pathogenesis and will infer novel sub-networks by combined analysis of proteomics and microarray data.
Many of the advances in structural molecular biology and related biosciences are the result of the rapidly occurring developments at synchrotrons. These include X-ray crystallography for protein structure determination, X-ray spectroscopy for examination of metalloprotein structure, and synchrotron footprinting technologies for examining macromolecular structure and dynamics. The Case School of Medicine of Case Western Reserve University recently established the Case Center for Proteomics and Bioinformatics, for expanding the state-of-the art in proteomics research. This Center provides administrative oversight for the Case Center for Synchrotron Biosciences (CSB) which is funded by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) as a Biotechnology Research Resource to serve an international community of biomedical scientists. The CSB is catalyzing further development and application of synchrotron radiation tools through a number of multidisciplinary collaborations and partnerships among an international community of scientists. The research facility located at the National Synchrotron Light Source (NSLS) at the Brookhaven National Laboratory (BNL) in New York. The NSLS, as a Department of Energy funded facility, has as a mission to provide academic institutions access to synchrotron light through various collaboration and consortium arrangements.
The Structural Genomics Project aims at determination of the 3D structure of all proteins. This aim can be achieved in four steps :
Under the direction of lead investigator Aaron Weinberg, professor and chair of the Department of Biological Sciences at the dental school, a team of 22 researchers will unravel changes in the human body.s innate immune system in HIV-infected people on antiretroviral therapies to provide new insights into how the body keeps us stay healthy.
A multidisciplinary team from dentistry and medicine will discover why HIV-infected humans receiving the class of drugs referred to as highly active anti-retroviral therapy (HAART) have increased the incidence of oral complications, such as a quadrupled rate of contracting human papillomavirus (HPV). This virus is more frequently associated with the genital tract and is now being seen in the mouth. Warts produced by HPV can lead to cancer and increased oral infections.
A powerful combination of protein separation techniques (two-dimensional gel electrophoresis and multi-dimensional high performance liquid chromatography), protein structural characterization techniques (mass spectrometry) and bioinformatics tools to link mass spectrometry data with genome database constitute the backbone of a newly emerged technology "proteomics". Current proteomic studies have three major categories:
The Proteomics Module will provide technical support for carrying out the three categories of proteomic studies as well as standard mass spectrometry analysis of bio-molecules for the vision research scientists at the Case Western Reserve University.
Bump hunting is a statistical learning method aimed at finding local and global extrema for problems in classification and regression settings. Recently, we have extended the scope of the method to high-dimensional data such as those arising from high-throughput molecular technologies, i.e. "omics" data, as generated e.g. by microarray, proteomics and high-throughput sequencing. One of the goals of the research project is to extend the scope of the method to any time-to-event response in high-dimensional settings such as survival. We are developing a new statistical strategy, called Survival Bump Hunting, which will allow to uncover hidden subgroups of individuals with different risk/survival in response (or not) to a treatment, and characterize them genomically and clinically. Ultimately, this is intended to improve diagnostics and prognostics of diseases as well as personalized medical interventions.
Contact PI: Jean-Eudes Dazard, PhD.