Dr. David A. Dichek |
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University of Washington School of Medicine Medicine Cardiology Professor of MedicineAppointed: 2001 University of Washington School of Medicine Medicine Cardiology Adjunct Professor of PathologyAppointed: 2001 |  |
Mailing AddressUniversity of Washington 1959 NE Pacific St. Box 357710 Seattle, Washington 98195-7710United States | Contact Information |
Qualifications
M.D., University of California, Los Angeles, 1984.
A.B. (magna cum laude), Princeton University, Romance Languages and Literatures, 1976.
Expertise and Research Interests
Research projects in our laboratory share a common theme: to understand the molecular mechanisms by which blood vessels become diseased. These investigations are pursued with the long-term goal of using our understanding of vascular disease mechanisms to develop gene-based interventions that prevent or reverse human vascular disease. There are three major areas of investigation: (1) development of gene transfer vectors capable of mediating long-term recombinant gene expression in vascular tissue; (2) clarifying the role of the uPA/plasminogen system in the pathogenesis of vascular disease; and (3) understanding the role of transforming growth factor beta1 (TGF-beta1) in vascular development and disease.
Development of Gene Transfer Vectors Capable of Mediating Long-Term Recombinant Gene Expression in Vascular Tissue
Arterial gene delivery has tremendous promise to serve as both an investigative and a therapeutic tool. Over the past several years (our first publication on vascular gene transfer was published in 1989), our laboratory and others' have reported the results of numerous investigations that illustrate this promise. However, as a result of technical limitations, arterial gene delivery remains underutilized. These limitations include low efficiency, inflammatory host reactions, and brevity of expression. These limitations are substantial; however, we believe they are surmountable.
Our goals are to develop improved vector systems and validate their utility as tools in investigations that provide clear, unambiguous answers to questions in arterial biology. Eventually, we expect to use these vectors as therapeutic agents to prevent or reverse arterial disease in humans. To generate improved vectors, we use modified adenoviral vectors that are less immunogenic. We recently showed that these modifications lead to prolonged transgene expression and decreased vascular inflammation. These vectors open the door to a new generation of arterial gene transfer experiments that define the roles of specific proteins in the arterial wall and suggest potent and specific new therapies for vascular diseases. We are currently performing experiments in which we express therapeutic genes in the blood vessels of experimental animals and test whether the genetically engineered blood vessels are protected from developing atherosclerosis.
Role of the uPA/Plasminogen System in the Pathogenesis of Vascular Disease
In addition to its well-established role in controlling thrombolysis, the uPA/plasminogen system contributes to several aspects of vascular homeostasis and the response to vascular injury. Expression of uPA is increased both in animal models of vascular disease and in diseased human blood vessels. However, these correlational data do not clarify whether uPA contributes to the progression of vascular disease or helps to prevent it. Plausible models can be constructed to support either view. To resolve these conundrums, we perform experiments in which uPA expression is manipulated at the level of the artery wall, and the effect of such manipulations on the development of vascular disease is determined. We manipulate vascular gene expression both by in vivo arterial gene transfer in adult animals and by germ line targeting of gene expression to cells that populate the arterial wall of transgenic mice. For example, we used germ line modifications to target overexpression of uPA to mouse macrophages and discovered that this resulted in accelerated atherosclerosis, coronary artery occlusions, and sudden death. We also found that overexpression of uPA in rabbit carotid artery endothelium causes vasoconstriction. This finding suggests that the uPA/plasminogen system may play a role in regulation of vascular tone. We are currently investigating the mechanisms through which uPA accelerates atherosclerosis and causes vasoconstriction.
Role of TGF-beta1 in the Development of Vascular Disease
As with the uPA/plasminogen system, the role of the cytokine TGF-beta1 in vascular biology is also controversial. TGF-beta1 is expressed in the artery wall, and its expression is increased in animal models of vascular disease and in some types of human arterial lesions. Reasonable arguments can be formulated that support both pro- and antiatherogenic roles for TGF-beta1. For example, TGF-beta1 may act primarily as a smooth muscle cell mitogen and as an inducer of cell migration and extracellular matrix synthesis. These activities would contribute to vascular lesion formation. It is also possible that arterial wall TGF-beta1 acts as a cytostatic and immunosuppressive agent, preventing smooth muscle cell division and decreasing vascular wall inflammation. These activities would prevent or mitigate atherosclerotic lesion formation. Reasonable arguments can also be formulated that support a role for TGF-beta1 in both aneurysm formation and aneurysm prevention. In animal models, increased TGF-beta1 signaling has been associated both with aneurysm formation and with arterial constriction. Therefore, the role of TGF-beta1 in aneurysm formation and prevention remains uncertain.
Our strategies for unraveling the biological role of TGF-beta1 are similar to those described above for uPA. Specifically, we use in vivo arterial gene transfer systems and transgenic mouse models to investigate the role played by vascular wall TGF-beta1 signaling in the development of vascular disease. The first of these studies, performed in rat carotid arteries, revealed that overexpression of TGF-beta1 stimulates intimal growth. This study also revealed an unanticipated consequence of TGF-beta1 overexpression: cartilaginous metaplasia of the vascular media. The presence of cartilaginous metaplasia revealed a surprising plasticity of the adult vascular smooth muscle phenotype and suggested that overexpression of TGF-beta1 may underlie the cartilaginous metaplasia observed in animal models of atherosclerosis and in degenerating human heart valves. We reproduced these observations in a newly developed mouse model of arterial gene transfer and have now used this model to elucidate the mechanisms through which TGF-beta1 stimulates intimal growth. Related experiments in progress use transgenic mice to investigate the consequences of overexpression of TGF-beta1 on atherosclerosis and aneurysm formation. Initially, this approach led to embryonic lethality and coincidentally revealed a critical role for TGF-beta1 in embryonic yolk sac vasculogenesis. We have now bypassed embryonic lethality with a conditional transgenic approach that permits TGF-beta1 overexpression in adult mice. A final aspect of this work involves experiments in which TGF-beta signaling is eliminated in smooth muscle cells of mice. As with overexpression, this approach also causes embryonic lethality. Analysis of embryos without TGF-beta signaling in smooth muscle cells is revealing insights into the role of TGF-beta signaling during vascular development.
Development of Gene Transfer Vectors Capable of Mediating Long-Term Recombinant Gene Expression in Vascular Tissue
Arterial gene delivery has tremendous promise to serve as both an investigative and a therapeutic tool. Over the past several years (our first publication on vascular gene transfer was published in 1989), our laboratory and others' have reported the results of numerous investigations that illustrate this promise. However, as a result of technical limitations, arterial gene delivery remains underutilized. These limitations include low efficiency, inflammatory host reactions, and brevity of expression. These limitations are substantial; however, we believe they are surmountable.
Our goals are to develop improved vector systems and validate their utility as tools in investigations that provide clear, unambiguous answers to questions in arterial biology. Eventually, we expect to use these vectors as therapeutic agents to prevent or reverse arterial disease in humans. To generate improved vectors, we use modified adenoviral vectors that are less immunogenic. We recently showed that these modifications lead to prolonged transgene expression and decreased vascular inflammation. These vectors open the door to a new generation of arterial gene transfer experiments that define the roles of specific proteins in the arterial wall and suggest potent and specific new therapies for vascular diseases. We are currently performing experiments in which we express therapeutic genes in the blood vessels of experimental animals and test whether the genetically engineered blood vessels are protected from developing atherosclerosis.
Role of the uPA/Plasminogen System in the Pathogenesis of Vascular Disease
In addition to its well-established role in controlling thrombolysis, the uPA/plasminogen system contributes to several aspects of vascular homeostasis and the response to vascular injury. Expression of uPA is increased both in animal models of vascular disease and in diseased human blood vessels. However, these correlational data do not clarify whether uPA contributes to the progression of vascular disease or helps to prevent it. Plausible models can be constructed to support either view. To resolve these conundrums, we perform experiments in which uPA expression is manipulated at the level of the artery wall, and the effect of such manipulations on the development of vascular disease is determined. We manipulate vascular gene expression both by in vivo arterial gene transfer in adult animals and by germ line targeting of gene expression to cells that populate the arterial wall of transgenic mice. For example, we used germ line modifications to target overexpression of uPA to mouse macrophages and discovered that this resulted in accelerated atherosclerosis, coronary artery occlusions, and sudden death. We also found that overexpression of uPA in rabbit carotid artery endothelium causes vasoconstriction. This finding suggests that the uPA/plasminogen system may play a role in regulation of vascular tone. We are currently investigating the mechanisms through which uPA accelerates atherosclerosis and causes vasoconstriction.
Role of TGF-beta1 in the Development of Vascular Disease
As with the uPA/plasminogen system, the role of the cytokine TGF-beta1 in vascular biology is also controversial. TGF-beta1 is expressed in the artery wall, and its expression is increased in animal models of vascular disease and in some types of human arterial lesions. Reasonable arguments can be formulated that support both pro- and antiatherogenic roles for TGF-beta1. For example, TGF-beta1 may act primarily as a smooth muscle cell mitogen and as an inducer of cell migration and extracellular matrix synthesis. These activities would contribute to vascular lesion formation. It is also possible that arterial wall TGF-beta1 acts as a cytostatic and immunosuppressive agent, preventing smooth muscle cell division and decreasing vascular wall inflammation. These activities would prevent or mitigate atherosclerotic lesion formation. Reasonable arguments can also be formulated that support a role for TGF-beta1 in both aneurysm formation and aneurysm prevention. In animal models, increased TGF-beta1 signaling has been associated both with aneurysm formation and with arterial constriction. Therefore, the role of TGF-beta1 in aneurysm formation and prevention remains uncertain.
Our strategies for unraveling the biological role of TGF-beta1 are similar to those described above for uPA. Specifically, we use in vivo arterial gene transfer systems and transgenic mouse models to investigate the role played by vascular wall TGF-beta1 signaling in the development of vascular disease. The first of these studies, performed in rat carotid arteries, revealed that overexpression of TGF-beta1 stimulates intimal growth. This study also revealed an unanticipated consequence of TGF-beta1 overexpression: cartilaginous metaplasia of the vascular media. The presence of cartilaginous metaplasia revealed a surprising plasticity of the adult vascular smooth muscle phenotype and suggested that overexpression of TGF-beta1 may underlie the cartilaginous metaplasia observed in animal models of atherosclerosis and in degenerating human heart valves. We reproduced these observations in a newly developed mouse model of arterial gene transfer and have now used this model to elucidate the mechanisms through which TGF-beta1 stimulates intimal growth. Related experiments in progress use transgenic mice to investigate the consequences of overexpression of TGF-beta1 on atherosclerosis and aneurysm formation. Initially, this approach led to embryonic lethality and coincidentally revealed a critical role for TGF-beta1 in embryonic yolk sac vasculogenesis. We have now bypassed embryonic lethality with a conditional transgenic approach that permits TGF-beta1 overexpression in adult mice. A final aspect of this work involves experiments in which TGF-beta signaling is eliminated in smooth muscle cells of mice. As with overexpression, this approach also causes embryonic lethality. Analysis of embryos without TGF-beta signaling in smooth muscle cells is revealing insights into the role of TGF-beta signaling during vascular development.
Other Expertise
American Board of Internal Medicine certification in Internal Medicine and Cardiovascular Diseases
Attending cardiologist at University of Washington Medical Center
Attending cardiologist at University of Washington Medical Center
Industrial Relevance
Expertise relevant to cardiovascular therapeutics and gene therapy
Keywords
COS Keywords:
Cardiology, Gene Therapy, Gene Transfer, Pathogenesis, Vascular Biology.Additional Terms:
Cardiology, Gene Therapy, Gene Transfer, Vascular Biology.Languages
(Reading, Writing, Speaking)
English: (Fluent, Fluent, Fluent)
French: (Fluent, Fluent, Fluent)
Swedish: (Functional, Basic, Functional)
Spanish: (Basic, Basic, Functional)
Memberships
American College of Physicians
American Heart Association
American Society for Gene Therapy
Federation of American Societies for Experimental Biology
Honors and Awards
2001, Editorial Board,
Arteriosclerosis, Thrombosis, and Vascular Biology
2001, Fellow,
American Heart Association
2001, John Locke, Jr. Family Endowed Chair in Cardiovascular Research and Treatment,
University of Washington
2000-2001,
Ad hoc reviewer,
Recombinant DNA Advisory Committee,
NIH
1999-2001,
Pathology A Study Section,
NIH
1998, Editorial Board,
Human Gene Therapy
1997, Fellow,
Council on Arteriosclerosis, Thrombosis, and Vascular Biology,
AHA
1997-1999,
Peer Review Committee,
California/Western Affiliate,
AHA
1996, Editorial Board,
Circulation
1996, Finalist, Irvine Page Young Investigator Award,
AHA
1996, Editorial Board,
Circulation Research
1995-1999,
Vascular Biology I Study Section,
National,
AHA
1984, Stafford Warren Medal,
UCLA School of Medicine
1983, Distinguished Scholar Award,
UCLA Graduate and Professional Schools
1980, Regent's Scholarship,
UCLA School of Medicine
1976, Phi Beta Kappa,
Princeton University
1976, Teaching Fellow,
Woodrow Wilson Nat'l Fellowship Foundation
Previous Positions
2000-2001, Professor,
University of California, San Francisco,
School of Medicine,
Medicine,
Cardiology
1994-2001, Associate Investigator,
University of California, San Francisco,
Gladstone Institute of Cardiovascular Disease
1994-2000, Associate Professor,
University of California, San Francisco,
School of Medicine,
Medicine,
Cardiology
1991-1994, Tenure track investigator,
NHLBI,
Molecular Hematology Branch
Publications
- Woodward, RN, Finn, AV, Dichek, DA, Identification of intracellular pathways through which TGF-beta1 upregulates PAI-1 expression in endothelial cells, Atherosclerosis, 186, 92-100, 2006
- Lee, S, Agah, M, Xiao, M, Frutkin, AD, Kremen, M, Shi, H, Dichek, DA, In vivo expression of a conditional TGF-beta1 transgene: No evidence for TGF-beta1 transgene expression in SM22alpha-tTA transgenic mice, J. Mol. Cell. Cardiol., 40, 148-156, 2006
- Otsuka, G, Agah, R, Frutkin, AD, Wight, TN, Dichek, DA, Transforming growth factor beta 1 induces neointima formation through plasminogen activator inhibitor-1-dependent pathways, Arterioscler. Thromb. Vasc. Biol., 26, 737-743, 2006
- Stempien-Otero, A, Plawman, A, Meznarich, J, Dyamenahalli, T, Otsuka, G, Dichek, DA, Mechanisms of cardiac fibrosis induced by urokinase plasminogen activator, J. Biol. Chem., 281, 15345-15351, 2006
- Frutkin, AD, Shi, H, Otsuka, G, Leveen, P, Karlsson, S, Dichek, DA, A critical developmental role for tgfbr2 in myogenic cell lineages is revealed in mice expressing SM22-Cre, not SMMHC-Cre, J. Mol. Cell. Cardiol., 41, 724-731, 2006
- Otsuka, G, Stempien-Otero, A, Frutkin, AD, Dichek, DA, Mechanisms of TFG-beta1-induced intimal growth: plasminogen-independent activities of plasminogen activator inhibitor-1 and heterogenous origin of intimal cells, Circ. Res., 100, 1300-1307, 2006
- Moriwaki, H, Stempien-Otero, A, Kremen, M, Cozen, AE, and Dichek, DA, Overexpression of urokinase by macrophages or deficiency of plasminogen activator inhibitor type 1 causes cardiac fibrosis in mice, Circ. Res., 95, 637-644, 16 Sep 2004
- Cozen, A, Moriwaki, H, Kremen, M, DeYoung, MB, Dichek, HL, Slezicki, KI, Young, SG, Vénient, M, Dichek, DA, Macrophage-targeted overexpression of urokinase causes accelerated atherosclerosis, coronary artery occlusions, and premature death, Circulation, 109, 2129-2135, 4 May 2004
- Wen, S, Graf, S, Massey, P, Dichek, DA, Improved vascular gene transfer with a helper-dependent adenoviral vector, Circulation, 110, 1484-1491, 2004
- Falkenberg, M, Tom, C, DeYoung, MB, Wen, S, Linnemann, R, Dichek, DA, Increased expression of urokinase during atherosclerotic lesion development causes arterial constriction and lumen loss, and accelerates lesion growth, Proceedings of the National Academy of Sciences (USA), 99, 10665-10670, 2002
- Wen, S, Driscoll, RM, Schneider, DB, Dichek, DA, Inclusion of the E3 region in an adenoviral vector decreases inflammation and neointima formation after arterial gene transfer, Arteriosclerosis, Thrombosis, and Vascular Biology, 21, 1777-1782, 2001
- DeYoung, MB, Tom, C, Dichek, DA, PAI-1 increases neointimal formation in balloon-injured rat carotid arteries, Circulation, 104, 1972-1977, 2001
- Camargo FD, Huey-Louie DA, Finn AV, Sassani AB, Cozen AE, Moriwaki H, Schneider DB, Agah R, Dichek DA, Germline incorporation of a replication-defective adenoviral vector in mice does not alter immune responses to adenoviral vectors, Molecular Therapy, 2(5), 496-504, November 2000
- Vines DJ, Lee SW, Dichek DA, Ellis V, Receptor-mediated regulation of plasminogen activator function: plasminogen activation by two directly membrane-anchored forms of urokinase, Journal of Peptide Science, 6(9), 432-9, September 2000
- Wen S, Schneider DB, Driscoll RM, Vassalli G, Sassani AB, Dichek DA, Second-generation adenoviral vectors do not prevent rapid loss of transgene expression and vector DNA from the arterial wall, Arteriosclerosis, Thrombosis, and Vascular Biology, 20(6), 1452-8, June 2000
- Agah R, Prasad KS, Linnemann R, Firpo MT, Quertermous T, Dichek DA, Cardiovascular overexpression of transforming growth factor-beta(1) causes abnormal yolk sac vasculogenesis and early embryonic death, Circulation Research, 86(10), 1024-30, 2000
- Kang SM, Braat D, Schneider DB, O'Rourke RW, Lin Z, Ascher NL, Dichek DA, Baekkeskov S, Stock PG, A non-cleavable mutant of Fas ligand does not prevent neutrophilic destruction of islet transplants, Transplantation, 69(9), 1813-7, 2000
- Schneider DB, Vassalli G, Wen S, Driscoll RM, Sassani AB, DeYoung MB, Linnemann R, Virmani R, Dichek DA, Expression of Fas ligand in arteries of hypercholesterolemic rabbits accelerates atherosclerotic lesion formation, Arteriosclerosis, Thrombosis, and Vascular Biology, 20(2), 298-308, February 2000
- Vassalli G, Agah R, Qiao R, Aguilar C, Dichek DA, A mouse model of arterial gene transfer: antigen-specific immunity is a minor determinant of the early loss of adenovirus-mediated transgene expression, Circulation Research [computer File], 85(9), e25-32, 1999
- DeYoung MB, Zamarron C, Lin AP, Qiu C, Driscoll RM, Dichek DA, Optimizing vascular gene transfer of plasminogen activator inhibitor 1, Human Gene Therapy, 10(9), 1469-78, 1999
- Rade JJ, Cheung M, Miyamoto S, Dichek DA, Retroviral vector-mediated expression of hirudin by human vascular endothelial cells: implications for the design of retroviral vectors expressing biologically active proteins, Gene Therapy, 6(3), 385-92, March 1999
- Schneider DB, Sassani AB, Vassalli G, Driscoll RM, Dichek DA, Adventitial delivery minimizes the proinflammatory effects of adenoviral vectors, Journal of Vascular Surgery, 29(3), 543-50, March 1999
- Veniant MM, Zlot CH, Walzem RL, Pierotti V, Driscoll R, Dichek D, Herz J, Young SG, Lipoprotein clearance mechanisms in LDL receptor-deficient 'Apo-B48-only' and 'Apo-B100-only' mice, Journal of Clinical Investigation, 102(8), 1559-68, 1998
- Schulick AH, Taylor AJ, Zuo W, Qiu CB, Dong G, Woodward RN, Agah R, Roberts AB, Virmani R, Dichek DA, Overexpression of transforming growth factor beta1 in arterial endothelium causes hyperplasia, apoptosis, and cartilaginous metaplasia, Proceedings of the National Academy of Sciences (USA), 95(12), 6983-8, 1998
- Gerszten RE, Lim YC, Ding HT, Snapp K, Kansas G, Dichek DA, Cabanas C, Sanchez-Madrid F, Gimbrone MA, Rosenzweig A, Luscinskas FW, Adhesion of monocytes to vascular cell adhesion molecule-1-transduced human endothelial cells: implications for atherogenesis, Circulation Research, 82(8), 871-8, 1998
- Schneider DB, Fly CA, Dichek DA, Geary RL, Adenoviral gene transfer in arteries of hypercholesterolemic nonhuman primates, Human Gene Therapy, 9(6), 815-21, 1998
- Qiu C, De Young MB, Finn A, Dichek DA, Cationic liposomes enhance adenovirus entry via a pathway independent of the fiber receptor and alpha(v)-integrins, Human Gene Therapy, 9(4), 507-20, 1998
- DeYoung MB, Dichek DA, Gene therapy for restenosis: are we ready?, Circulation Research, 82(3), 306-13, 1998
- Vassalli G, Dichek DA, Gene therapy for arterial thrombosis, Cardiovascular Research, 35(3), 459-69, September 1997
- Schulick AH, Vassalli G, Dunn PF, Dong G, Rade JJ, Zamarron C, Dichek DA, Established immunity precludes adenovirus-mediated gene transfer in rat carotid arteries. Potential for immunosuppression and vector engineering to overcome barriers of immunity, Journal of Clinical Investigation, 99(2), 209-19, 1997
- Creighton WM, Taylor AJ, Dichek DA, Dong G, Roberts AB, Schulick AH, Mannam P, Virmani R, Regional variability in the time course of TGF-beta 1 expression, cellular proliferation and extracellular matrix expansion following arterial injury, Growth Factors, 14(4), 297-306, 1997
- Gerszten RE, Luscinskas FW, Ding HT, Dichek DA, Stoolman LM, Gimbrone MA, Rosenzweig A, Adhesion of memory lymphocytes to vascular cell adhesion molecule-1-transduced human vascular endothelial cells under simulated physiological flow conditions in vitro, Circulation Research, 79(6), 1205-15, December 1996
- Dong G, Schulick AH, DeYoung MB, Dichek DA, Identification of a cis-acting sequence in the human plasminogen activator inhibitor type-1 gene that mediates transforming growth factor-beta1 responsiveness in endothelium in vivo, Journal of Biological Chemistry, 271(47), 29969-77, 1996
- al-Roof Higazi A, Aceto JF, Kniss D, Upson R, Cohen R, Dichek DA, Cines DB, Unesterified long chain fatty acids inhibit the binding of single chain urokinase to the urokinase receptor, Biochemistry, 35(21), 6884-90, 1996
- Dunn PF, Newman KD, Jones M, Yamada I, Shayani V, Virmani R, Dichek DA, Seeding of vascular grafts with genetically modified endothelial cells. Secretion of recombinant TPA results in decreased seeded cell retention in vitro and in vivo, Circulation, 93(7), 1439-46, 1996
- Rade JJ, Schulick AH, Virmani R, Dichek DA, Local adenoviral-mediated expression of recombinant hirudin reduces neointima formation after arterial injury, Nature Medicine, 2(3), 293-8, March 1996
- Dichek, D.A., Anderson, J,. Kelly, A.B., Hanson, S.R., Harker, L.A., Enhanced in vivo antithrombotic effects of endothelial cells expressing recombinant plasminogen activators transduced with retroviral vectors, Circulation, 93, 301-309, 1996
- Newman KD, Dunn PF, Owens JW, Schulick AH, Virmani R, Sukhova G, Libby P, Dichek DA, Adenovirus-mediated gene transfer into normal rabbit arteries results in prolonged vascular cell activation, inflammation, and neointimal hyperplasia, Journal of Clinical Investigation, 96(6), 2955-65, December 1995
- Schulick AH, Dong G, Newman KD, Virmani R, Dichek DA, Endothelium-specific in vivo gene transfer, Circulation Research, 77(3), 475-85, September 1995
- Schachtner SK, Rome JJ, Hoyt RF, Newman KD, Virmani R, Dichek DA, In vivo adenovirus-mediated gene transfer via the pulmonary artery of rats, Circulation Research, 76(5), 701-9, May 1995
- Schulick AH, Newman KD, Virmani R, Dichek DA, In vivo gene transfer into injured carotid arteries. Optimization and evaluation of acute toxicity, Circulation, 91(9), 2407-14, 1995
- Rome JJ, Shayani V, Newman KD, Farrell S, Lee SW, Virmani R, Dichek DA, Adenoviral vector-mediated gene transfer into sheep arteries using a double-balloon catheter, Human Gene Therapy, 5(10), 1249-58, October 1994
- Shayani V, Newman KD, Dichek DA, Optimization of recombinant t-PA secretion from seeded vascular grafts, Journal of Surgical Research, 57(4), 495-504, October 1994
- Dichek DA, Lee SW, Nguyen NH, Characterization of recombinant plasminogen activator production by primate endothelial cells transduced with retroviral vectors, Blood, 84(2), 504-16, 1994
- Lee SW, Ellis V, Dichek DA, Characterization of plasminogen activation by glycosylphosphatidylinositol-anchored urokinase, Journal of Biological Chemistry, 269(4), 2411-8, 1994
- Rome JJ, Shayani V, Flugelman MY, Newman KD, Farb A, Virmani R, Dichek DA, Anatomic barriers influence the distribution of in vivo gene transfer into the arterial wall. Modeling with microscopic tracer particles and verification with a recombinant adenoviral vector, Arteriosclerosis and Thrombosis, 14(1), 148-61, January 1994
- Lee SW, Trapnell BC, Rade JJ, Virmani R, Dichek DA, In vivo adenoviral vector-mediated gene transfer into balloon-injured rat carotid arteries, Circulation Research, 73(5), 797-807, November 1993
- Dichek DA, Gene transfer in the treatment of thrombosis, Thrombosis and Haemostasis, 70(1), 198-201, 1993
- Jaklitsch MT, Biro S, Casscells W, Dichek DA, Transduced endothelial cells expressing high levels of tissue plasminogen activator have an unaltered phenotype in vitro, Journal of Cellular Physiology, 154(1), 207-16, January 1993
- Kahn ML, Lee SW, Dichek DA, Optimization of retroviral vector-mediated gene transfer into endothelial cells in vitro, Circulation Research, 71(6), 1508-17, December 1992
- Polvino WJ, Dichek DA, Mason J, Anderson WF, Molecular cloning and nucleotide sequence of cDNA encoding a functional murine low-density-lipoprotein receptor, Somatic Cell and Molecular Genetics, 18(5), 443-50, September 1992
- Lee SW, Kahn ML, Dichek DA, Expression of an anchored urokinase in the apical endothelial cell membrane. Preservation of enzymatic activity and enhancement of cell surface plasminogen activation, Journal of Biological Chemistry, 267(18), 13020-7, 1992
- Flugelman MY, Jaklitsch MT, Newman KD, Casscells W, Bratthauer GL, Dichek DA, Low level in vivo gene transfer into the arterial wall through a perforated balloon catheter, Circulation, 85(3), 1110-7, March 1992
- Flugelman MY, Virmani R, Leon MB, Bowman RL, Dichek DA, Genetically engineered endothelial cells remain adherent and viable after stent deployment and exposure to flow in vitro, Circulation Research, 70(2), 348-54, February 1992
- Newman KD, Nguyen N, Dichek DA, Quantification of vascular graft seeding by use of computer-assisted image analysis and genetically modified endothelial cells, Journal of Vascular Surgery, 14(2), 140-6, August 1991
- Dichek DA, Retroviral vector-mediated gene transfer into endothelial cells, Molecular Biology and Medicine, 8(2), 257-66, April 1991
- Dichek DA, Nussbaum O, Degen SJ, Anderson WF, Enhancement of the fibrinolytic activity of sheep endothelial cells by retroviral vector-mediated gene transfer, Blood, 77(3), 533-41, 1991
- Dichek DA, Neville RF, Zwiebel JA, Freeman SM, Leon MB, Anderson WF, Seeding of intravascular stents with genetically engineered endothelial cells, Circulation, 80(5), 1347-53, November 1989
- Dichek D, Quertermous T, Thrombin regulation of mRNA levels of tissue plasminogen activator and plasminogen activator inhibitor-1 in cultured human umbilical vein endothelial cells, Blood, 74(1), 222-8, July 1989
- Dichek D, Quertermous T, Variability in messenger RNA levels in human umbilical vein endothelial cells of different lineage and time in culture, In Vitro Cellular and Developmental Biology, 25(3 Pt 1), 289-92, March 1989
- Dichek DA, Holmvang G, Fallon JT, Kantor HL, Miller SW, Dinsmore RE, Singer DE, Buckley MJ, Fifer MA, Angiosarcoma of the heart: three-year survival and follow-up by nuclear magnetic resonance imaging, American Heart Journal, 115(6), 1323-4, June 1988
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