Idell, Steven, M.D., Ph.D.
Vice President for Research
Temple Univ. School of Medicine, M.D., 1977
Temple Univ. School of Medicine, Ph.D., 1978
- Sept 1986-Sept 1991 Recipient, Clinical Investigator Award K08HL01603, National Institutes of Health N.H.L.B.I.
- Sept 1996-Present Appointed Chair Holder, Temple Chair in Idiopathic Pulmonary Fibrosis. The first endowed chair at UT Health Northeast.
- 1977-78 Intern, Internal Medicine, Temple University Hospital, Philadelphia, PA.
- 1978-80 Resident, Internal Medicine, Temple University Hospital, Philadelphia, PA.
- 1980 Board Certified, Internal Medicine, Am Board of Internal Medicine, No 77898.
- 1980-83 Fellow, Pulmonary Disease Section, Temple University Hosp., Philadelphia, PA.
- 1982 Board Certified Pulmonary Disease, Am. Board Int. Med. No. 77898.
- 1984-88 Assistant/Associate Professor of Medicine, Temple University Health Science Center
and UT Health Northeast (UT Health Northeast); Director, Medical ICUs.
- 1988 Professor of Medicine and Chief, Pulmonary Division, The University of Texas Health Science
Center at Tyler (UT Health Northeast).
- 1996-03 Chairman, Department of Specialty Care Services, all medical specialties, UT Health Northeast.
- 2003 Senior Vice President for Research, UT Health Northeast Currently serving in this capacity.
- 2011 NIH SMARTT Review Panel.
- 2012-13 Chair, NIH Translational PO-1 Review Panel.
- 2013 Dean, School of Medical Biological Sciences, UT Health Northeast.
- 2014 NIH VITA Advisory Board.
Coagulation, Fibrinolysis, Regulation of Gene Expression, Acute and Chronic Lung Injury, Pleural Injury, Lung and Pleural Neoplasia.
- Control of the fibrin turnover in pleural disease.
- Development of new therapeutics for lung and pleural fibrosis.
Current Grant Support:
- NIH 1P50 HL 107186-01
NIH/NHLBI - S. Idell (Contact); A. Komissarov (Co-PI)
PAI-1 Targeted Intrapleural Fibrinolytic Therapy
The primary goals of this project are to test various strategies that target plasminogen activator inhibitor-1 (PAI-1) in the preclinical treatment of pleural loculation. The objective of this work is to determine if PAI-1-targeted approaches confer advantages that are of potential clinical benefit over current pharmacologic approaches in anticipation of future clinical trial testing of PAI-1 targeted interventions that prove to be effective in our models of pleural injury.
- NHLBI SMARTT Idell/Mazar (PI)
scuPA for the Treatment of Complicated Parapneumonic Effusions
The NHLBI Science Moving towArds Research Translation and Therapy program (SMARTT) contract facilitates the translation of novel discoveries into successful new therapies for heart, lung, and blood diseases. Support for cGMP manufacturing, GLP-compliant pharmacology/toxicology IND-enabling studies and regulatory support is provided for an IND submission for the zymogen form of urokinase, scuPA. (No specified end date).
Completed Research Support:
- NIH 1R21HL097216-01A2
NIH/NHLBI - Tang, H. (PI)
PKD Family Kinase Function and Signaling in Lung Fibroblasts
This project will test the hypothesis that PKD family kinases may play critical roles in lung fibroblast biology, including the fibroblast activation, proliferation, and the production of extracellular matrix, which may offer novel drugable targets for halting the progression of idiopathic pulmonary fibrosis.
- NIH PO1 HL 076406-05
NIH/NHLBI - Idell S. (PI)
Fibrinolytic Pathways in Lung Injury and Repair
This project will elucidate novel pathways by which the fibrinolytic system influences acute injury and repair in the lung and pleural compartment. There is no overlap with the present application.
- NIH RAID 1 XO-1NS063898-01A1 - S. Idell (PI)
IND-enabling toxicology, pharmacology and safety studies of recombinant scuPA for treatment for plueral loculation. This is a grant to perform toxicology studies on scuPA, a drug that will be prepared for clinical trial testing through work done as part of this grant. There is no overlap with the current project.
- FAMRI Clinical Innovator Award - S. Shetty (PI)
Control of PAI-1 in passive smoke exposure
In these studies the role of PAI-1 in the control of lung epithelial cell viability and airway remodeling induced by passive smoke exposure in mice will be determined. There is no overlap with the studies proposed in this application.
- NIH 1R21HL093547-01 - S. Shetty (PI)
Regulation of lung epithelial injury by plasminogen activator inhibitor-1
The primary goal of this project is to evaluate how p53-induced PAI-1 and inhibition of PAI-1 expression contributes to cellular adhesion to vitronectin, Akt phosphorylation, death receptor and mitochondrial pathways of apoptosis during airway and alveolar epithelial injury and to determine if p53-induced PAI-1 expression and its inhibition contribute to polymorphonuclear leukocyte (PMN) efferocytosis by macrophages during lung injury. No overlap with the studies proposed in this application. Role: Co-investigator.
- FAMRI - Idell S (PI)
PAI-1 and Airway Remodeling in Passive Smoke Exposure
In this project, we evaluated the role of PAI-1 in control of proteolysis and lung remodeling induced by exposure of mice to passive smoke exposure.
Extravascular fibrin deposition accompanies diverse types of tissue injury and neoplasia. In the setting of acute and chronic lung injury, the fibrin gel forms a transitional matrix that undergoes remodeling associated with invasion by inflammatory cells and fibroblasts. These cells express procoagulants and fibrinolysins that govern the transformation of the transitional fibrin gel into fibrotic tissue. A similar process accounts for the desmolastic response that surrounds various tumors, including lung cancers and malignant mesothelioma. Tumors also invade host tissues via remodeling of the transitional fibrin gel.
We have been, and remain interested in the elucidation of how pathways of fibrin deposition; coagulation and fibrinolysis influence the course of acute and chronic lung injuries. More recently, we have also studied the role of these processes in the pathogenesis of malignant mesothelioma. We are currently studying how expression of various fibrinolysins, procoagulants and their inhibitors are regulated at the posttranscriptional level and how these molecules influence cellular function via signaling mechanisms.
Selected Papers and Abstracts:
(Selected from a total of 142)
- Colice G, Idell S. Pro/Con: Should Fibrinolysins Routinely Be Used For Treatment of Complicated Parapneumonic Pleural Effusions. Chest. In press. 2013.
- Tucker TA, Jeffers A, Alvarez A, Owens S, Koenig K, Quaid B, Komissarov AA, Florova G, Kothari H, Pendurthi U, Rao LV, Idell S. Plasminogen activator inhibitor-1 deficiency augments visceral mesothelial organization, intrapleural coagulation and lung restriction in mice with carbon black/bleomycin-induced pleural injury. Am J Respir Cell Mol Biol. 2013 Sep 11. [Epub ahead of print].
- Komissarov AA, Florova G, Azghani A, Karandashova S, Kurdowska AK, Idell S. Active α-macroglobulin is a reservoir for urokinase after fibrinolytic therapy in rabbits with tetracycline-induced pleural injury and in human pleural fluids. Am J Physiol Lung Cell Mol Physiol. 2013 Aug 30. [Epub ahead of print].
- Florova G, Karandashova S, Declerck PJ, Idell S, Komissarov AA. Remarkable Stabilization of Plasminogen Activator Inhibitor 1 in a "Molecular Sandwich" Complex. Biochemistry. 2013 Jun 25. [Epub ahead of print].
- Tucker T, Idell S. Plasminogen-plasmin system in the pathogenesis and treatment of lung and pleural injury. Semin Thromb Hemost. 2013 Jun;39(4):373-81. doi: 10.1055/s-0033-1334486. Epub 2013 Mar 16. PMID: 23504608.
- Komissarov AA, Stankowska D, Krupa A, Fudala R, Florova G, Florence J, Fol M, Allen TC, Idell S, Matthay MA, Kurdowska AK. Novel aspects of urokinase function in the injured lung: role of α2-macroglobulin. Am J Physiol Lung Cell Mol Physiol. 2012 Dec 15;303(12):L1037-45. doi: 10.1152/ajplung.00117.2012. Epub 2012 Oct 12. PMID: 23064953.
- Karandashova S, Florova G, Azghani AO, Komissarov AA, Koenig K, Tucker TA, Allen TC, Stewart K, Tvinnereim A, Idell S. Intrapleural adenoviral delivery of human plasminogen activator inhibitor-1 exacerbates tetracycline-induced pleural injury in rabbits. Am J Respir Cell Mol Biol. 2013 Jan;48(1):44-52. doi: 10.1165/rcmb.2012-0183OC. Epub 2012 Sep 20. PMID: 23002099.
- Tucker TA, Williams L, Koenig K, Kothari H, Komissarov AA, Florova G, Mazar AP, Allen TC, Bdeir K, Mohan Rao LV, Idell S. Lipoprotein receptor-related protein 1 regulates collagen 1 expression, proteolysis, and migration in human pleural mesothelial cells. Am J Respir Cell Mol Biol. 2012 Feb;46(2):196-206. doi: 10.1165/rcmb.2011-0071OC. PMID: 22298529.
- Komissarov AA, Florova G, Idell S. Effects of extracellular DNA on plasminogen activation and fibrinolysis. J Biol Chem. 2011 Dec 9;286(49):41949-62. doi: 10.1074/jbc.M111.301218. Epub 2011 Oct 5. PMID: 21976662.
- Williams L, Tucker TA, Koenig K, Allen T, Rao LV, Pendurthi U, Idell S. Tissue factor pathway inhibitor attenuates the progression of malignant pleural mesothelioma in nude mice. Am J Respir Cell Mol Biol. 2012 Feb;46(2):173-9. doi: 10.1165/rcmb.2010-0276OC. Epub 2011 Aug 18. PMID: 21852688.
- Sen P, Komissarov AA, Florova G, Idell S, Pendurthi UR, Vijaya Mohan Rao L. Plasminogen activator inhibitor-1 inhibits factor VIIa bound to tissue factor. J Thromb Haemost. 2011 Mar;9(3):531-9. doi: 10.1111/j.1538-7836.2010.04167.x. PMID: 21143380.
- Nassar T, Yarovoi S, Fanne RA, Akkawi S, Jammal M, Allen TC, Idell S, Cines DB, Higazi AA. Regulation of airway contractility by plasminogen activators through N-methyl-D-aspartate receptor-1. Am J Respir Cell Mol Biol. 2010 Dec;43(6):703-11. doi: 10.1165/rcmb.2009-0257OC. Epub 2010 Jan 22. PMID: 20097831.
- Idell S, Jun Na M, Liao H, Gazar AE, Drake W, Lane KB, Koenig K, Komissarov A, Tucker T, Light RW. Single-chain urokinase in empyema induced by Pasturella multocida. Exp Lung Res. 2009 Oct;35(8):665-81. doi: 10.3109/01902140902833277. PMID: 19895321.
- Shetty S, Velusamy T, Shetty RS, Marudamuthu AS, Shetty SK, Florova G, Tucker T, Koenig K, Shetty P, Bhandary YP, Idell S. Post-transcriptional regulation of plasminogen activator inhibitor type-1 expression in human pleural mesothelial cells. Am J Respir Cell Mol Biol. 2010 Sep;43(3):358-67. doi: 10.1165/rcmb.2009-0046OC. Epub 2009 Oct 23. PMID: 19855086.
- Komissarov AA, Mazar AP, Koenig K, Kurdowska AK, Idell S. Regulation of intrapleural fibrinolysis by urokinase-alpha-macroglobulin complexes in tetracycline-induced pleural injury in rabbits. Am J Physiol Lung Cell Mol Physiol. 2009 Oct;297(4):L568-77. doi: 0.1152/ajplung.00066.2009. Epub 2009 Aug 7. PMID: 19666776.
- Tucker TA, Dean C, Komissarov AA, Koenig K, Mazar AP, Pendurthi U, Allen T, Idell S. The urokinase receptor supports tumorigenesis of human malignant pleural mesothelioma cells. Am J Respir Cell Mol Biol. 2010 Jun;42(6):685-96. Epub 2009 Jul 27. PMID:19635932