1985 - PharmD, Pharmacy, University of Michigan College of Pharmacy
1986 - Residency, Clinical Pharmacy, University of Illinois at Chicago
1988 - Fellowship, Cardiovascular Research, State University of New York
1996 - Fellowship, Pulmonary Research, University of Colorado Health Sciences Center, Webb Waring Institute for Antioxdant Research
Professional Training and Experience
1985-86 - Clinical Pharmacy Practice Residency, University of Illinois at Chicago
1986-88 - Fellowship in Cardiovascular Research, State University of New York at Buffalo
1988-97 - Assistant Professor of Pharmacy, School of Pharmacy, University of Colorado Health Sciences Center
1994-96 - American Foundation for Pharmaceutical Education Basic Science Fellowship
1997-2007 - Associate Professor of Pharmacy, School of Pharmacy, University of Colorado Health Sciences Center
2003-2007 - Associate Professor, Graduate School, University of Colorado Health Sciences Center
2003-2007 - Associate Member, University of Colorado Cancer Center
2007- 2012 - Associate Professor, Department of Clinical Sciences, College of Pharmacy, University of Michigan
2012- present - Professor, Department of Clinical Sciences, College of Pharmacy, University of Michigan
Lung injury is mediated by inflammation and the loss of homeostasis in coagulation and fibrinolysis.
There are more than 130 different therapeutic proteins or peptides that are used to treat a broad range of illnesses. One of these proteins, tissue plasminogen activator (tPA), has been used to treat myocardial infarction and stroke. Dr. Stringer's laboratory has determined that in addition to its proteolytic function, tPA has anti-inflammatory activity. The combination of these two properties could make tPA a viable therapeutic approach to treat inflammatory-fibrotic lung diseases such as acute respiratory distress syndrome (ARDS) and idiopathic pulmonary fibrosis (IPF) and the rare, most often pediatric disease, plastic bronchitis (PB). To this end, the Stringer laboratory has developed a formulation of tPA (pf-tPA) for targeted pulmonary delivery and is focused on three main areas of research:
Pulmonary Delivery of Therapeutic Proteins
Candidate therapeutic proteins are formulated for pulmonary delivery using a range of assays to assess protein stability. Aerodynamic particle size and biological function following nebulization are measured to ensure the feasible of candidate formulations. Respiratory deposition is also characterized in experimental models of pulmonary dosing and of acute lung injury in order to gather pharmacodynamic, pharmacokinetic and toxicological as well as therapeutic response data. Collectively, this line of investigation enables the Stringer laboratory to test the feasibility of local pulmonary delivery of therapeutic proteins in man.
Pathogenesis of Inflammatory-Fibrin Lung Diseases
Pulmonary illnesses such as acute lung injury (ALI)/ARDS, IPF and PB remain clinically challenging problems for a number of reasons including poorly understood complex physiology and patient heterogeneity. The absence of biomarkers that predict disease onset, progression and severity have had a negative impact on our ability to identify and develop effective pharmacotherapy aimed at improving morbidity and mortality in patients with critical illness. The Stringer research group is utilizing a broad systems biology approach that encompasses metabolomics, proteomics, transcriptomics, and genomics with the powerful tool of computational analysis. The work is aimed at identifying the metabolic signatures of ALI and PB.
Mechanisms and Disposition of Therapeutic Proteins in Inflammatory Lung Disease
Inflammatory lung disease is a significant risk to human health. Presently, the Stringer lab is focused on optimizing the use of pf-tPA for the treatment of PB. We are optimizing dosing strategies using ex vivo approaches that utilize cast from patients with PB. In addition, the lab is developing an animal model of PB that encompasses elements of derangement of the fibrinolytic and inflammatory systems so that a more accurate assessment of pf-tPA efficacy and safety in the treatment of PB can be made.
Baik J, Mane G, Stringer KA, Rosania GR. A macrophage mediated xenobiotic sequestration response induced by the bioaccumulating poorly soluble compound, clofazimine, under revision.
Yuan SY, Ellingrod VL, Schipper M, Stringer KA, Cai X, Hayman JA, Yu J, Lawrence TS, Kong F-M. Genetic variations in TGFß1, tPA and ACE and radiation-induced thoracic toxicities in patients with non-small cell lung cancer. J Thoracic Oncology, accepted for publication.
Caruthers RL, Kempa M, Loo A, Gulbransen, E, Kelly E, Erickson E, Hirsch JC, Schumacher KR, Stringer KA. Demographic characteristics and estimated prevalence of Fontan-associated plastic bronchitis. Pediatr Cardiol. 2012 Jul 15. [Epub ahead of print].
Suresh MV, Wagner MC, Rosania GR, Stringer KA, Min KA and Reddy RC. Pulmonary administration of water-soluble curcumin complex reduces acute lung injury severity. Am J Respir Cell Mol Biol 2012 Feb 3. [Epub ahead of print] PMC journal- in process
Yu J, Zheng N, Mane G, Min K-A, Hinestroza JP, Zhu H, Stringer KA, Rosania GR. A cell-based computational modeling approach for developing site-directed molecular probes, PLoS Computational Biology, 2012 Feb;8(2):e1002378. Epub 2012 Feb 23. PMCID3285574.
Karnovsky A, Weymouth T, Hull T, Tarcea VG, Scardoni G, Laudanna C, Sartor M, Stringer KA, Jagadish HV, Burant C, Athey B, Omenn GS. Metscape 2 bioinformatics tool for the analysis and visualization of metabolomics and gene expression data. Bioinformatics. 2012 Feb 1;28(3):373-80. Epub 2011 Nov 30. PMCID3268237.
Heath L, Ling S, Racz J, Southard S, Schmidt L, Myers J, Tsai WC, Caruthers RL, Hirsch JC, Stringer KA. Longitudinal pathological assessment and responsiveness of plastic bronchitis casts to tissue plasminogen activator. Pediatr Cardiol 2011 Dec;32(8):1182-9. Epub 2011 Jul 24. PMCID3207025.
Serkova NJ, Standiford TJ, Stringer KA. The emerging field of quantitative blood metabolomics for biomarker identification in critical illnesses. Am J Resp Crit Care Med, 2011 Sep 15;184(6):647-55. Epub 2011 Jun 16. PMCID3208597
Stringer KA, Serkova NJ, Karnovsky A, Guire K, Paine R, Standiford TJ. Metabolic consequences of sepsis-induced acute lung injury as revealed by 1H-nuclear magnetic resonance spectroscopy of plasma. Am J Physiol Lung Cell Molec Physiol 2011;300:L4-L11. 2010 Oct 1. [Epub ahead of print]. Accompanying editorial L1-3. PMCID3023293
Lackowski NP, Pitzer JE, Tobias M, Van Rheen Z, Nayar R, Mosharaff M, Stringer KA. Safety of repeated, prolonged administration of a pulmonary formulation of tissue plasminogen activator in mice. Pulm Pharmacol Therap 2010;23:107-14. PMCID28219.
Stringer KA, Tobias M, Dunn JS, Campos J, Van Rheen Z, Mosharraf M, Nayar R. Accelerated dosing frequency of a pulmonary formulation of tissue plasminogen activator is well-tolerated in mice. Clin Exp Pharmacol Physiol 2008; 35:1454-60. PMCID2779770
Serkova NJ, Van Rheen Z, Tobias M, Pitzer JE, Wilkinson JE, Stringer KA. Utility of magnetic resonance imaging and nuclear magnetic resonance-based metabolomics for the quantification of inflammatory lung injury. Am J Physiol Lung Cell Molec Physiol 2008;295:L152-61. PMCID2494785
Stringer KA, Tobias M, O’Neill HC, Franklin CF. Cigarette smoke extract-induced suppression of caspase-3-like activity impairs human neutrophil phagocytosis. Am J Physiol Lung Cell Mol Physiol 2007;292:L1572-9.
MacLaren R, Stringer KA. The emerging role of anti-coagulants and fibrinolytics in the treatment of acute lung injury. Pharmacotherapy 2007;27:860-73. PMCID2515375