Clinical Translational Research is the effective translation of new knowledge, mechanisms, and techniques generated by advances in basic science research into new approaches for prevention, diagnosis, and treatment of disease, essential for improving health.
The first collaboration on translational research between Advocate Lutheran General Hospital and Chicago Medical School (CMS) brought together basic scientists and clinicians to develop clinically significant research projects. As part of this collaborative translational research initiative, eight pilot projects were jointly funded.
The collaboration team consists of Russell Research Institute’s director Nancy Cipparrone and Dr. Ronald S. Kaplan of Rosalind Franklin University (RFUMS). Dr. Kaplan is the Vice President for Research, RFUMS, as well as the Vice Dean for Research, CMS. The main areas of research include neuroscience, neurodegenerative disease, diabetes, cancer, structural biology, cystic fibrosis, lower extremity, ambulatory research, drug discovery, and cardiac resuscitation.
The eight current projects, including a brief summary of each, are listed below.
Innate Immune Dysregulation in the Pathogenesis of Pyoderma Gangrenosum
Marylee Braniecki, MD; Fabio Re, PhD; Barbara Vertel, PhD
Department of Pathology (LGH); Microbiology & Immunology and Cell Biology & Anatomy (CMS)
Pyoderma gangrenosum (PG) is a diagnostically challenging ulcerative skin condition known as a “disease of exclusion” because the tools necessary for its diagnosis have yet to be identified. Based on the hypothesis that pyoderma gangrenosum is caused by a dysregulation of immune cell mediated responses; this study aims to develop a profile of PG inflammatory biomarkers to implement a diagnostic tool that would accurately identify PG. The overall goals of this research are to provide a better understanding of pyoderma gangrenosum that will ultimately improve our diagnostic and therapeutic approach for this disease, as well as other related ulcerative conditions.
Plasma MicroRNAs as Biomarkers of Residual Disease in Breast Cancer
Heidi C. Memmel, MD, FACS; Chao-Lan Yu, PhD; Jaime Palma, BS; Weihua Gao, MS
Department of Surgery (LGH); Cellular and Molecular Pharmacology (CMS); Center for Clinical and Translational Sciences in the Design and Analysis Core (UIC)
This study aims to indentify in blood, a microRNA signature that can measure remaining breast cancer cells upon treatment. It involves the collection of blood of patients diagnosed with breast cancer undergoing breast surgery, and the potential collection of fresh tumor and or stromal tissue, all to be inspected in a laboratory for specific traits. The expected outcome of this project is the development of a low-invasive approach to identify biomarkers to measure disease remission and clinical efficacy of treatment in breast cancer.
Role of Tumor Microenvironment in Inflammatory Breast Cancer
Neelam Sharma-Walia; Heidi C. Memmel, MD, FACS
Department of Microbiology & Immunology (CMS); Surgery (LGH)
Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer with a recurrence rate as high as 50%. Since diagnosis, prognosis and management are based on knowledge gained in non-IBC tumors and are irrelevant to IBC, the immediate need to understand IBC biology, to evaluate its unique inflammatory and angiogenic growth factor rich tumor microenvironment (TME) is imperative. This study aims to determine the hallmark differences between non-IBC and IBC cell lines at the level of TME and mammosphere characteristics. The role of IBC TME on mammospheres cultured from non-IBC cells will be evaluated as well as the effect of serum/serum derived nanovesicles from healthy controls and IBC patients on mammosphere characteristics.
Comparison of Human Infragenicular Arteries to Assess the Molecular Determinants and Functional Correlates of Oxidative Stress in Type-2 Diabetes
Carl White, PhD; Samer F. Najjar, MD
Department of Physiology & Biophysics (CMS); Surgery (LGH)
The anterior and posterior tibial arteries suffer greater physiological impairment than the peroneal artery during peripheral artery disease. The purpose of this study is to understand this and to assess the potential of stimulating cellular antioxidant production to improve arterial function. This is done by conducting experiments on anterior and posterior tibial and peroneal arteries isolated from below-knee amputations performed on diabetic patients. This project will provide insight into the cellular mechanisms that define peripheral artery disease and take the first step toward testing the feasibility of a treatment approach that relieves oxidative stress to improve vascular function.
Plasma Cytochrome c as Biomarker of Traumatic Injury and Predictor of Outcome
Raúl J. Gazmuri, MD, PhD, FCCM; Manoj Shah, MD
Resuscitation Institute (CMS); Trauma Services (LGH)
Cytochrome c is a mitochondrial protein that plays a key role in energy metabolism. When mitochondria are injured, cytochrome c may leave mitochondria and reach the bloodstream. By measuring cytochrome c levels in plasma in trauma patients who require intubation for mechanical ventilation and survive to hospital admission, this study aims to investigate whether circulating cytochrome c levels may serve as biomarker of traumatic injury correlating with severity of traumatic injury, development of organ dysfunction, and clinical outcomes. The successful completion of this study will identify severity, predict outcomes, and assess novel mitochondrial protective strategies.
Probing Human Nasal Epithelial Cells for In Vitro Pharmacogenomic Studies for the Treatment of Cystic Fibrosis
Robert J. Bridges, PhD; Neil Bradbury, PhD; Gabriel Aljdeff, MD
Department of Physiology and Biophysics (CMS); Pediatric Pulmonology (LGH)
Cystic Fibrosis (CF) is a recessive genetic disease caused by over 1,900 different mutations in a single gene coding for the anion channel protein CFTR. Kalydeco is the only current FDA approved treatment of CF patients with the G551D mutation, however its high cost prohibits testing all CF patients. The current study aims to establish in vitro diagnostic methods to determine the responsiveness of CF nasal epithelial cells to Kalydeco as well as other drugs currently in the CF drug discovery pipeline.
Omental Stem Cell Participation in Wound Healing
Daniel A. Peterson, PhD; Loren S. Schechter, MD; Iris A. Seitz, MD, PhD
Department of Neuroscience (CMS); Surgery (LGH)
Omental tissue has been shown clinically to improve healing but it is not clear whether the promotion of wound healing may be due to stem cells arising from adipose tissue or if the stroma of the omentum may contain a distinct resident population of stem cells. This study is directly engrafting human omental cell populations, human adipose stem cells, and human amnion-derived cells to directly compare their efficacy at promoting wound closure in a mouse model of impaired wound healing. This study goal is to identify stem cell populations and characterize their expression of therapeutic factors aiming to generate new therapeutic delivery systems.
Role of Angiogenin in Breast Cancer Metastasis
Bala Chandran, PhD; Imad Almanaseer, MD
Department of Microbiology and Immunology (CMS); Pathology (LGH)
Breast cancer is the number two killer of women of all races world-wide. Excellent prognosis with long term remission for many subtypes of this heterogeneous disease critically depends on the extent of invasiveness of the primary tumor and its complete removal by surgical interventions. The single most critical event that controls “leading edge” migration in tumors is plasminogen degradation by the plasminogen activation complex (PAC). While neither the precise mechanism of this process nor the complete interactome of the PAC has been identified, recent evidence suggests Angiogenin (ANG), a proangiogenic factor highly expressed and secreted by several types of cancer cells, may play a critical role in plasminogen degradation and cell motility. The purpose of this study is to identify and decipher the molecular machinery of breast cancer cell migration by using invitro cell culture systems and archival specimens of paraffin-embedded biopsy tissue samples from post-breast cancer surgery patients and normal healthy individuals. The primary techniques used in the analysis for the presence of PAC and ANG are immunofluorescence and immunohistochemical methods. The goal of this study is to identify both bonafied markers for detecting the extent of invasion and novel targets for arresting cancer cell motility and metastasis.