Selected Works of Sergio Jiménez, MD, MACR
My current research includes:
Study of Caveolin-1 and Allograft Inflammatory Factor 1 in Scleroderma.
Bodily organs and tissues are made up of individual cells, held together by a connective tissue also known as extracellular matrix that is constantly being degraded and regenerated. When there is excessive production or defective breakdown of extracellular matrix, or a combination of both, the result is tissue fibrosis, the scarring that damages the skin and internal organs of Scleroderma patients. Studies in our laboratories have discovered that two novel proteins may be involved in the earliest stages of the process of tissue fibrosis. These proteins are allograft inflammatory factor 1 and caveolin-1. We are continuing our research studies to identify the precise role of these proteins and to block their participation in the accumulation of extracellular matrix in scleroderma cells maintained in culture in our laboratories. The successful identification of the mechanisms of action of these two proteins may lead to the development of novel treatments for patients with Scleroderma.
Identification of biomarkers of Scleroderma disease severity and progression.
The extent and severity of skin fibrosis in Scleroderma are currently only assessed by cutaneous examination and palpation (a physician feels the texture and thickness of skin), a method which is non-quantitative, highly subjective, and usually not very reproducible. Two of our projects aim to remedy this serious lack. The first project employs global gene expression and proteomics followed by mass spectrometry analysis to identify valuable biomarkers that can provide reliable and accurate information regarding the severity, progression, or response to therapy for a particular SSc patient. The second project employs highly sophisticated methods of confocal immunomicroscopy to accurately quantitate the biochemical content and location of molecular components of the fibrous tissues.
Other studies include:
Testing novel therapeutic agents to inhibit the exaggerated production of fibrotic tissue by Scleroderma fibroblasts.
These studies are based on extensive prior experimental results from numerous research laboratories, including our own, and are aimed at testing potentially effective therapeutic agents in the laboratory by employing scleroderma skin cells in culture to identify the most promising candidate drugs with the potential to be developed into effective treatments for Scleroderma.
Treatment of pulmonary fibrosis in experimental animals employing an aerosol delivering novel peptides capable of entering cells without a requirement for viral vectors.
This study takes an innovative approach to treatment of pulmonary fibrosis, one of the most serious and often lethal complications of Scleroderma, by employing small molecules that are capable of being shuttled inside cells without using viral vectors. These studies have the potential to develop an inhaler to deliver the effective drugs directly into the lung cells for the treatment of pulmonary fibrosis.
Creation of a new animal model of Scleroderma.
At present there is no animal model which reproduces the clinical and pathologic features of Scleroderma. In these studies we will inject various types of cells obtained from the blood of Scleroderma patients into immune-deficient mice to completely replace the immune cells from the mouse with immune cells from the patient. These studies will allow the identification of which particular cells are involved in the induction of Scleroderma alterations and to test potentially effective therapeutic agents.
Sergio A. Jimenez
Director, The Scleroderma Center
Co-Director, Jefferson Institute of Molecular Medicine
Professor and Director, Division of Connective Tissue Diseases, Jefferson Medical College
Thomas Jefferson University
233 South 10th Street Philadelphia, Pennsylvania 19107 United States
PHONE: (215) 503-5042