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.
- Chris T. Derk and Sergio A. Jimenez (2004) Following the molecular pathways toward an understanding of the pathogenesis of systemic sclerosis, Annals of Internal Medicine, 140(1):37-50
- Nora Sandorfi, Natalia Louneva, Elena Hitraya, Gyorgy Hajnoczky, Biagio Saitta, and Sergio A. Jimenez (2005) Inhibition of Collagen Gene Expression in Systemic Sclerosis Dermal Fibroblasts by Mithramycin, Annals of the Rheumatic Diseases, vol64, iss12, pp.1685-1691
- Francesco Del Galdo and Sergio A. Jimenez (2007) T cells expressing allograft inflammatory factor 1 display increased chemotaxis and induce a profibrotic phenotype in normal fibroblasts in vitro, Arthritis & Rheumatism, 56(10):3478-3488
- Francesco Del Galdo, Gerd G. Maul, Sergio A. Jimenez, and Carol M. Artlett (2006) Expression of allograft inflammatory factor 1 in tissues from patients with systemic sclerosis and in vitro differential expression of its isoforms in response to transforming growth factor beta, Arthritis & Rheumatism, vol. 54, iss. 8, pp. 2616-2625
- Natalia Louneva, Gonzalo Huaman, Joanna Fertala, and Sergio A. Jimenez (2006) Inhibition of systemic sclerosis dermal fibroblast type I collagen production and gene expression by simvastatin, Arthritis & Rheumatism, 54(4):1298-1308
- Sergio A. Jimenez, Carol M. Artlett, Nora Sandorfi, Chris T. Derk, Kevin Latinis, Heloisa Sawaya, Richard Haddad, and Joseph C. Shanahan (2004) Dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy): study of inflammatory cells and transforming growth factor beta1 expression in affected skin, Arthritis & Rheumatism, 50(8):2660-2666
- Biagio Saitta, Svetlana Gaidarova, Lucia Cicchillitti, and Sergio A. Jimenez (2000) CCAAT binding transcription factor binds and regulates human COL1A1 promoter activity in human dermal fibroblasts: demonstration of increased binding in systemic sclerosis fibroblasts, Arthritis & Rheumatism, 43(10):2219-2229
- Carol M. Artlett, Lori A. Cox, and Sergio A. Jimenez (2000) Detection of cellular microchimerism of male or female origin in systemic sclerosis patients by polymerase chain reaction analysis of HLA-Cw antigens, Arthritis & Rheumatism, 43(5):1062-1067
- Roswitha Sgonc, Hermann Deitrich, Claudia Sieberer, Georg Wick, Paul J. Christner, and Sergio A. Jimenez (1999) Lack of endothelial cell apoptosis in the dermis of tight skin 1 and tight skin 2 mice, Arthritis & Rheumatism, 42(3):581-584
- Elena G. Hitraya, John Varga, Carol M. Artlett, and Sergio A. Jimenez (1998) Identification of elements in the promoter region of the alpha1(I) procollagen gene involved in its up-regulated expression in systemic sclerosis, Arthritis & Rheumatism, 41():2048-2058
- Elena G. Hitraya and Sergio A. Jimenez (1996) Transcriptional activation of the alpha 1(I) procollagen gene in systemic sclerosis dermal fibroblasts:. Role of intronic sequences., Arthritis & Rheumatism, 39(8):1347-1354
- Lucia Cicchillitti, Sergio A. Jimenez, Arturo Sala, and Biaggio Saitta (2004) B-Myb acts as a repressor of human COL1A1 collagen gene expression by interacting with Sp1 and CBF factors in scleroderma fibroblasts, Biochemical Journal, 378:609-616
- David G. Stokes, Gang Liu, Rita Dharmavaram, David Hawkins, Sonsoles Piera-Velazquez, and Sergio A. Jimenez (2001) Regulation of type-II collagen gene expression during human chondrocyte de-differentiation and recovery of chondrocyte-specific phenotype in culture involves Sry-type high-mobility-group box (SOX) transcription factors, Biochemical Journal, 360:461-470
- Francesco Del Galdo, Carol M. Artlett, and Sergio A. Jimenez (2006) The role of allograft inflammatory factor 1 in systemic sclerosis, Current Opinion in Rheumatology, vol18, iss6, pp.588-593
- Sonsoles Piera-Velazquex, David F. Hawkins, Mary Kate Whitecavage, David C. Colter, Sergio A. Jimenez, and David A. Stokes (2007) Regulation of the human SOX9 promoter by Sp1 and CREB, Experimental Cell Research, 313(6):1069-1079
- Carol Artlett, Ken I. Welsh, Carol M. Black, and Sergio A. Jimenez (1997) Fetal-maternal HLA compatibility confers susceptibility to systemic sclerosis, Immunogenetics, 47(1):17-22
- Young H Lee, Joya Sahu, Marie S O'Brien, Vivette D D'Agati, and Sergio A. Jimenez (2011) Scleroderma renal crisis-like acute renal failure associated with mucopolysaccharide accumulation in renal vessels in a patient with scleromyxedema.
- Svetlana Gaidarova and Sergio A. Jimenez (2002) Inhibition of basal and transforming growth factor-beta-induced stimulation of COL1A1 transcription by the DNA intercalators, mitoxantrone and WP631, in cultured human dermal fibroblasts, Journal of Biological Chemistry, 277(41):38737-38745
- Cay M. Kielty, Michael Raghunath, Linda D. Siracusa, Michael J. Sherratt, Reiner Peters, C. Adrian Shuttleworth, and Sergio A. Jimenez (1993) The tight skin mouse: demonstration of mutant fibrillin-1 production and assembly into abnormal microfibrils, Journal of Cell Biology, 140(5):1159-1166
- Sergio A. Jimenez, Svetlana Gaidarova, Biagio Saitta, Nora Sandorfi, David J. Herrich, Joan C. Rosenbloom, Umberto Kucich, William R. Abrams, and Joel Rosenbloom (2001) Role of protein kinase C-delta in the regulation of collagen gene expression in scleroderma fibroblasts, Journal of Clinical Investigation, 108:1395-1403
- E. Munoz, D. Suri, S. Amini, K. Khalili, and Sergio A. Jimenez (1995) Stimulation of alpha 1(I) procollagen gene expression in NIH-3T3 cells by the human T cell leukemia virus type 1 (HTLV-1) tax gene., Journal of Clinical Investigation, 96(5):2413-2420
- Carol M. Artlett, Shu-Jen Chen, John Varga, and Sergio A. Jimenez (1998) Modulation of basal expression of the human alpha1(I) procollagen gene (COL1A1) by tandem NF-1/Sp1 promoter elements in normal human dermal fibroblasts, Matrix Biology, 17(6):425-434
- Carol M. Artlett, J. Bruce Smith, and Sergio A. Jimenez (1998) Identification of fetal DNA and cells in skin lesions from women with systemic sclerosis, New England Journal of Medicine, 338(17):1186-1191
- J A. Roman-Blas, D G. Stokes, and S. A. Jimenez (2007) Modulation of TGF-β signaling by proinflammatory cytokines in articular chondrocytes, Osteoarthritis and Cartilage, 15(12):1367-1377
- Fabian A. Mendoza, Carol M. Artlett, Nora Sandorfi, Kevin Latinis, Sonoles Piera-Velazquez, and Sergio A. Jimenez (2006) Description of twelve cases of nephrogenic fibrosing dermopathy and review of the literature, Seminars in Arthritis and Rheumatism, vol35, iss4, pp.238-249