## Curriculum Vitae

**Name:** Thomas Henrik Bugge, Ph.D.

**Place of Birth:** Copenhagen, Denmark

**Citizenship:** Danish (U.S. Permanent Resident)

**Education:**

1989. M.Sc., Molecular Biology, The Institute of Microbiology,
      University of Copenhagen, Copenhagen, Denmark.

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1993. Ph.D., Molecular Biology, European Molecular Biology Laboratory
      (EMBL), Heidelberg, Germany.

**Brief Chronology of Employment:**

1987-1989 Pregraduate (M.Sc.) student, Laboratory of Tumor Virology, The
Fibiger Institute, Copenhagen, Denmark.

1990-1993 Graduate studies in molecular biology, EMBL, Heidelberg,
Germany.

1993-1995 Postdoctoral Fellow, The Finsen Laboratory, State University
Hospital, Copenhagen, Denmark/ Children\'s Hospital Research Foundation,
Cincinnati, Ohio.

1995-1996 Research Leader, The Finsen Laboratory, State University
Hospital, Copenhagen, Denmark.

1997--1999 Associate Professor of Pediatrics, Children\'s Hospital
Research Foundation, Cincinnati, Ohio.

1999--present Chief, Proteases and Tissue Remodeling Unit, Oral and
Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial
Research, National Institutes of Health, Bethesda, MD.

**Honors and Other Special Scientific Recognition:**

1989. Pregraduate Fellowship, The Danish Cancer Society, Copenhagen,
      Denmark.

      1993. Predoctoral Fellowship, EMBL, Heidelberg, Germany.

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      1991. Travel Grant, The Danish Research Academy, Aarhus, Denmark.

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      1992. Travel Grant, The Danish Research Academy, Aarhus, Denmark.

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      1993. Fellowship, The Danish Cancer Research Foundation,
            Copenhagen, Denmark.

      1994. Travel Grant, The Danish Plasmid Foundation, Glostrup,
            Denmark.

1994 -1995 Senior Researcher, The Danish Medical Research Council,
Denmark.

1996. Received the \"1996 Creativity Award\" at the XIIIth International
      Congress on Fibrinolysis and Thrombolysis, Barcelona, Spain.

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1999. Abstract Selection Committee, "The First Meeting of the
      International Proteolysis Society", Mission Point Resort, Mackinac
      Island, MI.

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1999. Co-organizer, "The First Meeting of the International Proteolysis
      Society", Mission Point Resort, Mackinac Island, MI.

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2002. Discussion Moderator "Forbeck Symposium on Proteases as Cancer
      Therapeutic Targets" Captiva Island, FL.

2002 Scientific Advisory Board, "The Second Meeting of the International
Proteolysis Society", Munich, Germany.

2002 Session Chair, Proteolysis in Cancer, "The Second Meeting of the
International Proteolysis Society", Munich, Germany.

2002. Ad Hoc Reviewer, Promotion of Li Zhang to Associate Scientist,
      Department of Vascular Biology, American Red Cross, Rockville,
      M.D.

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2002. Ad Hoc Reviewer, Promotion of Dr. Shijie Sheng, Department of
      Pathology, Wayne State University to Associate Professor with
      Tenure, Detroit, MI.

2003. Ad Hoc Reviewer, Promotion of Dr. Chen-Yong Lin, Lombardi Cancer
      Center, Georgetown University Medical Center.

2003 \"NIDCR Staff Award\" for Services to the National and
International Research Communities.

2003 \"NIDCR EEO Special Achievement Award\" for \"Extraordinary
Initiative in Promoting Diversity and Career Development for Students
and Fellows and Successfully Recruiting Underrepresented Minority
Students\".

2004 Chair, Plenary Session I, XVIIth International Congress on
Fibrinolysis and Proteolysis, Melbourne, Australia, (March 21-25, 2004).

2005 Organizer (with Dudley Strickland, Toni Antalis, and Dan Lawrence)
"The Xth International Workshop on Molecular and Cellular Biology of
Plasminogen Activation", Washington, D.C.

2005 Selected for NIH Director\'s Seminar Series, NIH, Bethesda, MD.

2006 International Organizing Committee, International Society for
Fibrinolysis and Proteolysis Meeting, San Diego, August 27-31.

2006 Session Chair, Transmembrane Proteases/Extracellular Proteolysis,
Gordon Conference on Plasminogen Activation and Extracellular
Proteolysis. February 19-24, Ventura, CA.

2008 Vice Chair, Gordon Conference on Plasminogen Activation and
Extracellular Proteolysis.

2010 Chair, Gordon Conference on Plasminogen Activation and
Extracellular Proteolysis.

#### 

#### 

#### Editorial Recognition of Research Publications

1\. Vassalli, J.-D. and Saurat, J. H. (1996). Cuts and scrapes? Plasmin
heals! *Nature Medicine,* **2**, 284.

2\. Mosesson. M. W. (2000). Fibrinogen as a determinant of the
metastatic potential of tumor cells. *Blood*, **96**, 3301.

3\. Pawlak, S. and Strickland, S. (2002). Tissue plasminogen activator
and seizures: a clot-buster's secret life. *J. Clin. Invest.*,
**109**,1529-1531.

4\. Huchinson, E. (2003). Mass destruction. *Nature Reviews Cancer*,
**3**, 82.

5\. Brown, H. (2003). Engineered anthrax toxin has potent antitumour
activity. *Lancet Oncology*, **4**, 64.

6.  Herz, J. (2003). LRP: a bright beacon at the blood brain barrier.
    *J. Clin. Invest.,* **112**, 1483-1485.

7.  Site-specific conversion of a pro-fusion protein toxin. (2004)
    *Blood*, **104**, 1919.

8.  Tumors feed on collagen. (2005). *J. Cell Biol.* **169**, 977-986.

9.  Cancer: the matrix is now in control (2005) *Nature Medicine* **11**
    1156-1159.

10. Journal Club (2005) *Nature* **438**, 534-535.

**Invited lectures and presentations since 1995:**

1\. Bristol-Myers Squibb Lecture, Annual Meeting, Danish Cancer Research
Society, Copenhagen, Denmark.

2\. Plenary Lecture, 2nd Joint Meeting of the Wound Healing Society &
The European Tissue Repair Society, Boston, MA.

3\. Prize Lecture, XIIIth International Congress on Fibrinolysis and
Thrombolysis, Barcelona, Spain.

4\. 1996 Gordon Conference on Proteolytic Enzymes and their Inhibitors.
New London, NH.

5\. Seminar Speaker, The Danish Biological Society, Copenhagen, Denmark.

6\. Seminar Speaker, Institute of Microbiology, University of
Copenhagen, Copenhagen, Denmark.

7\. Seminar Speaker, Tulane Medical School, Department of Biochemistry,
New Orleans, LA.

8\. Seminar Speaker, SUNY at Stony Brook, Department of Immunology and
Pathology, Stony Brook, NY.

9\. Seminar Speaker, Arris Pharmaceuticals, South San Francisco, CA.

10\. Seminar Speaker, Uniklinik Freiburg, University of Freiburg,
Freiburg, Germany.

11\. Seminar Speaker, Differentiation Programme, EMBL, Heidelberg,
Germany.

12\. Seminar Speaker, State University Hospital, Copenhagen, Denmark.

13\. Plenary Speaker, 17th International Congress of Biochemistry and
Molecular Biology/American Society of Biochemistry and Molecular
Biology, San Francisco, CA.

14\. Seminar Speaker, Roche Bioscience, Palo Alto, CA.

15\. Seminar Speaker, Affinity Group Seminar Series, Scripps Research
Institute, San Diego, CA.

16\. Seminar Speaker, Department of Vascular Biology, American Red
Cross, Rockville, MD.

17\. Seminar Speaker, The Burnham Institute, Department of Cell
Adhesion-Extracellular Matrix Biology, San Diego, CA.

18\. Seminar Speaker, "Molecular Medicine Seminar Series", University of
Umea, Umea, Sweden.

19\. Seminar Speaker, American Association for Cancer Research and ACTA
Pathologica Microbiologica Immunologica Scandinavica meeting on
"Proteases and Protease Inhibitors in Cancer", Nyborg, Denmark.

20\. Seminar Speaker, State University Hospital, Copenhagen, Denmark.

21\. Seminar Speaker, The National Institute of Dental and Craniofacial
Research, The National Institutes of Health, Bethesda, MD.

22\. Grand Rounds Speaker, Karmanos Cancer Institute, Wayne State
University, Detroit, MI.

23. Speaker, Developmental Biology Protease Symposium, Wayne State
    University, Detroit, MI.

24\. Speaker, Protease Consortium Meeting, Vanderbilt University,
Nashville, TN.

25\. Speaker, Melbourne Matrix Metalloproteinase Mini-Symposium,
Melbourne, Australia.

26. Seminar Speaker, Craniofacial Development and Regeneration Branch,
    National Institute of Dental and Craniofacial Research, National
    Institutes of Health, Bethesda, MD.

27. Seminar Speaker, Oral Infection and Immunity Branch, National
    Institute of Dental and Craniofacial Research, National Institutes
    of Health, Bethesda, MD.

28. Seminar Speaker, Gene Therapy and Therapeutics Branch, National
    Institute of Dental and Craniofacial Research, National Institutes
    of Health, Bethesda, MD.

29. Seminar Speaker, Entremed, Rockville, MD.

30. Seminar Speaker, Novo/Nordisk A/S, Maaloev, Denmark.

31. Seminar Speaker, State University Hospital, Copenhagen, Denmark.

32. Seminar Speaker, Corvas International, Inc., San Diego, CA.

33. Seminar Speaker, Department of Vascular Biology, American Red Cross.

34. Seminar Speaker, Oral Infection and Immunity Branch, National
    Institute of Dental and Craniofacial Research, National Institutes
    of Health, Bethesda, MD.

35. Seminar Speaker, Laboratory of Cellular Carcinogenesis and Tumor
    Promotion, National Cancer Institute, Bethesda, MD.

36. Seminar Speaker, Lombardi Cancer Center, Georgetown University
    Medical Center, Washington, D. C.

37. Seminar Speaker, Gordon Conference on Proteolytic Enzymes and Their
    Inhibitors, New London, NH.

38. Seminar Speaker, American Association for Cancer Research,
    Proteases, Extracellular Matrix and Cancer, Hilton Head, SC.

39. Seminar Speaker, "Peptide Toxins Targeted to Cancer Symposium:
    Experience from animal studies and clinical trials". Copenhagen,
    Denmark.

40. Seminar Speaker, State University Hospital, Copenhagen, Denmark.

41. Speaker, National Cancer Institute-sponsored workshop on "Proteases
    and Cancer: Biology and Clinical Applications Workshop", Bethesda,
    MD.

42. Speaker, Immunology/Cell Biology Seminar series, NCI-Frederick,
    Frederick, MD.

43. Speaker, Celera, South San Francisco, CA.

44. Seminar Speaker, 47^th^ Annual Meeting of the Society of Thrombosis
    and Haemostasis Research, Innsbruck, Austria.

45. Seminar Speaker, EMBL, Monterotondo, Italy.

46\. Speaker, Laboratory of Cell Biology, National Heart Lung and Blood
Institute, Bethesda, MD.

47\. Seminar Speaker**,** 32^nd^ Annual Meeting of Danish Society for
Biochemistry and Molecular Biology.

48\. Speaker, Gordon Conference on Plasminogen Activation and
Extracellular Proteolysis. 2004, Ventura, CA

49\. Plenary Speaker, XVIIth International Congress on Fibrinolysis and
Proteolysis, Melbourne, Australia, (March 21-25, 2004).

50\. Seminar Speaker, National Institute of Child Health, NIH, Bethesda,
MD.

51\. Invited speaker, Second Meeting of the American Society for Matrix
Biology, San Diego, CA.

52\. Seminar Speaker Department of Pharmacology, Wayne State University,
Detroit, MI.

53\. Seminar Speaker, Department of Pathology, Wayne State University,
Detriot, MI.

54\. NIH Director\'s Seminar Series, NIH, Bethesda, MD.

55\. Seminar Speaker, Department of Cancer Biology, M. D. Anderson
Cancer Center, Houston, TX.

56\. Seminar Speaker, Department of Pharmacology, SUNY at Stony Brook,
Stony Brook, NY

57\. Speaker, Molecular Medicine Department, University of Michigan,
Michigan, MI. 8/11/2005.

58\. Speaker, Transmembrane Proteases/Extracellular Proteolysis, Gordon
Conference on Plasminogen Activation and Extracellular Proteolysis.
Ventura, CA. 2/21/06.

59\. Speaker, Society of Biomolecular Screening, Baltimore, MD, 4/3/06.

60\. Speaker, International Society for Fibrinolysis and Proteolysis
Meeting, San Diego, August 27-31, 2006.

61\. Speaker, Laboratory of Cell Biology, National Heart Lung and Blood
Institute, September 14, 2006.

62\. Key Note Speaker, 3rd Annual European Cancer Degradome Meeting,
Nov. 7-9, 2006.

63\. Speaker, Symposium Honoring the 70^th^ Birthday of Professor Keld
Danø, Nov 11, 2006.

**Grants**

1995-1996 Vera and Carl Johan Michaelsen Foundation Grant, "
Investigation of the Molecular mechanisms of cancer invasion and
metastasis by gene targeting", \$ 20,000.

1997-1998 Board of Trustees Grant, Children's Hospital Research
Foundation, "Determination of the role of the plasminogen activation
system in cancer invasion and metastasis by tumor transplantation
studies in plasminogen-deficient mice", \$ 80,000.

1997- 2001 Danish Medical Research Council, "Transgenic molecular
genetic analysis of the function and interaction of matrix degrading
protease systems in tissue remodeling and cancer invasion", \$ 29,000.

1998-2003 NIH/NCI, RO1, CA79994-01, "Coagulation and Fibrinolysis in
Tumor Progression". (Initial Review Group Priority Score 133, Percentile
1.4) Total Direct Costs: \$ 750,786. Grant relinquished after the
transfer of research program to the NIH Intramural Program.

1999-2001 Supplement to NIH/NCI, RO1 CA79994-01, "Protease
Consortium/Coagulation and Fibrinolysis in Tumor Progression." Grant
relinquished after the transfer of the research program to the NIH
intramural program.

1999 Board of Trustees Grant, Children's Hospital Research Foundation
(extension), "Determination of the role of the plasminogen activation
system in cancer invasion and metastasis by tumor transplantation
studies in plasminogen-deficient mice", \$ 6,600.

1999--2000 NIH/NCI, R13, CA82133-01, (Co-investigator; P.I. Dr. B. F.
Sloane) "Conference of the International Proteolysis Society." Total
Direct Costs: \$ 7,500.

2002--2005 DOD/Breast Cancer Center of Excellence (Subcontract P.I.;
P.I. Dr. B. F. Sloane) "Validation of Proteases as Therapeutic Targets
in Breast Cancer: Functional Imaging of Protease Expression, Activity
and Inhibition." Total Direct Costs: \$ 5,700,000. Subcontract PTRU \$
197,207.

2003-2005 NIAID Support of Intramural Biodefense Research from ICs other
than NIAID," Imaging Anthrax Toxin Proteolytic Activation." Total Direct
Costs: \$ 463,016.

2005 Imaging Probe Development Center (IPDC) Award, Molecular Imaging
Roadmap Initiative.

2006-2008 NIAID Support of Intramural Biodefense Research from ICs other
than NIAID," Anthrax Toxin Intoxication-Molecular Imaging and
Identification of Novel Candidate Agents for Post-Exposure Treatment of
Anthrax" Total Direct Costs: \$ 498,782.

# 

# Administration 

1999-present Institutional Animal Care and Use Committee, NIDCR.

1999-present Gene Targeting Facility Oversight Committee, NIDCR.

1999-2003 Animal Care Facility Oversight Committee, NIDCR.

1999. NIH Central Vivarium Animal Research Center Core Planning
      Committee

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2003. NIDCR Veterinary Resources Core Contracts Technical Evaluation
      Panel.

2004-present Chair, Institutional Animal Care and Use Committee, NIDCR.

2006 Organizer, NIDCR Tenure-Track Seminar Series

2006-present Member, NIDCR Promotion and Tenure Committee.

**Patents**

First Inventor:

> "In vivo imaging of cell-surface protease activity using modified
> anthrax toxins." DHHS Ref No. E-295-01/0 (Co-inventors, Dr. Shi-Hui
> Liu, Dr. Stephen Leppla, and David Mitola). *Pending*

Co-inventor:

> "Mutated anthrax toxin protective antigen proteins that specifically
> target cells containing high amounts of cell-surface
> metalloproteinases or plasminogen activator receptors.\" DHHS Ref
> No.E-293-99/1; PCT/US00/26192. First Inventor: Stephen Leppla.
> *Pending*
>
> \"Exploiting the Multimeric Nature of Certain Protein Toxins to Target
> Cells Having More than One Identifying Characteristic", First
> Inventor: Stephen Leppla. *Submitted*
>
> \"Activation of recombinant diphtheria toxin fusion proteins by
> specific proteases highly expressed on the surface of tumor cells\",
> First Inventor: Stephen Leppla. *Submitted*

# Editorial Responsibilities

# 

# 2002-present Handling Editor, Thrombosis and Haemostasis

2003-2005 Editorial Board, Oral Oncology

2005 Guest Editor, Thrombosis and Haemostasis Theme Issue: Amalfi to
Washington D.C. - Twenty Years of Plasminogen Activator Research.

2005 Editor, Proteases and Cancer, in Methods in Molecular Biology,
Humana Press, USA

2006 Editor, Frontiers in Bioscience, "Type II Transmembrane Serine
Proteases" Issue

### Study Sections etc.

2003 Ad Hoc Member, American Cancer Society, Cell Structure and
Metastasis Committee.

2003 Congressionally Directed Medical Research Programs, Prostate Cancer
Research Program, Pathobiology-2.

2004. Regular Member, American Cancer Society, Cell Structure and
      Metastasis Committee.

2004 Ad Hoc reviewer, The Telethon Foundation, Italy

2005 Ad Hoc Reviewer, German Research Council, "Tumor Vessel Interface"
Priority Program

2006 NCI sponsored Think Tank: Imaging Tumors and Their
Microenvironment, June 8--10, 2006, Alexandria, Virginia

2006 Ad Hoc Reviewer, Austrian Science Fund.

# Ad Hoc Journal Review

> AfCS-Nature Signaling Gateway
>
> American Journal of Pathology
>
> American Journal of Respiratory Cell and Molecular Biology
>
> Arthritis and Rheumatism
>
> Bioorganic & Medicinal Chemistry Letters
>
> Blood
>
> Cancer Research
>
> Circulation
>
> Clinical Cancer Research
>
> Developmental Cell
>
> EMBO Journal
>
> International Journal of Cancer
>
> Journal of the National Cancer Institute
>
> Journal of Investigative Dermatology
>
> Molecular and Cellular Biology
>
> Molecular Carcinogenesis
>
> Neoplasia
>
> Nature Genetics
>
> Nature Medicine
>
> Nature Reviews Microbiology
>
> Oncogene
>
> Proceedings of the National Academy of Sciences (USA)
>
> The Journal of Biological Chemistry
>
> The Journal of Cell Biology
>
> The Journal of Cellular Biochemistry
>
> The Journal of Cell Science
>
> The Journal of Clinical Investigation
>
> The Journal of Clinical Pathology
>
> The Journal of Histochemistry and Cytochemistry
>
> Thrombosis and Haemostasis
>
> The Journal of Immunology
>
> Trends in Cardiovascular Medicine

Bibliography

1\) Andreassen, H., Bohr, H., Bohr, J., Brunak, S., Bugge, T.,
Cotterill, R. M., Jacobsen, C., Kusk, P., Lautrup, B., Petersen, S. B.,
Sæhrmark, T., and Ulrich, K. (1990). Analysis of the secondary structure
of the human immunodeficiency virus (HIV) proteins p17, gp120, and gp41
by computer modeling based on neural networks methods. *J. Acquir.
Immune. Defic. Syndr.,* 6, 615-622.

2\) Bugge, T. H., Lindhardt, B. Ø., Hansen, L. L., Kusk, P., Hulgaard,
E. F., Holmbäck, K., Klasse, P. J., Zeuthen, J., and Ulrich, K. (1990).
Analysis of a highly immunodominant epitope in the human
immunodeficiency virus type 1 transmembrane glycoprotein, gp41, defined
by a human monoclonal antibody. *J. Virol.*, **64**, 4123-4129.

3\) Bugge, T. H., Hansen, L. L., Lindhardt, B. Ø., Kvinesdal, B., Kusk,
P., Holmbäck, K., Hulgaard, E. F., and Ulrich K. (1991). Competition
ELISA using a human monoclonal antibody for the detection of antibodies
against human immunodeficiency virus type 1. *J. Virol. Methods,*
**32**, 1-10.

4\) Kusk, P., Bugge, T. H., Lindhardt, B. Ø., Hulgaard, E. F., and
Holmbäck, K. (1992). Mapping of linear B-cell epitopes on the major core
protein p24 of human immunodeficiency virus type 1 (HIV-1). *AIDS Res.
Hum. Retroviruses,* **8**, 1789-1794.

5\) Kusk, P., Lindhardt, B. Ø., Bugge, T. H., Holmbäck, K., and
Hulgaard, E. F. (1993). Mapping of a new immunodominant human linear
B-cell epitope on the vpu protein of the human immunodeficiency virus
type 1. *J. Acquir. Immune. Defic. Syndr.,* **6**, 334-338.

6\) Holmbäck, K., Kusk, P., Hulgaard, E. F., Bugge, T. H., Scheibel, E.,
and Lindhardt, B. Ø. (1993). Autologous antibody response against the
principal neutralizing domain of human immunodeficiency virus type 1
isolated from infected humans. *J. Virol.,* **67***,* 1612-1619.

7\) Kusk, P., Holmbäck, K., Lindhardt, B. Ø., Hulgaard, E. F., and
Bugge, T. H. (1992). Mapping of two new human B-cell epitopes on HIV-1
gp120. *AIDS*, **6**, 1451-1456.

8\) Disela, C., Glineur, C., Bugge, T., Sap, J., Stengl, G., Dodgson,
J., Stunnenberg, H. G., Beug, H., and Zenke, M. (1991). v-erbA
overexpression is required to extinguish c-erbA function in erythroid
cell differentiation and regulation of the erbA target gene CA II.
*Genes & Dev.*, **5**, 2033-2047.

9\) Vivanco-Ruiz, M. M, Bugge, T. H., Hirchmann, P., and Stunnenberg H.
G. (1991). Functional characterization of a natural retinoic acid
responsive element. *EMBO J.*, **10**, 3829-3838.

10\) Bugge, T. H., Pohl, J., Lonnoy, O., and Stunnenberg, H. G. (1992).
RXRα, a promiscuous partner of retinoic acid and thyroid hormone
receptors. *EMBO J.*, **11**, 1409-1418.

11\) Barettino, D., Bugge, T. H., Bartunek, P., Vivanco-Ruiz, M. D.,
Sonntag-Buck, V., Beug, H., Zenke, M., and Stunnenberg, H. G. (1993).
Unliganded T3R, but not its oncogenic variant v-erbA suppresses RAR
dependent transactivation by titrating out RXR. *EMBO J.*, **12**,
1343-1354.

12\) Islam, T. C., Bugge, T. H., and Bohm, S. (1993). The long terminal
repeat of VL30 retrotransposons contains sequences that determine
retinoic acid-induced transcription in cultured keratinocytes. *J. Biol.
Chem.*, **268**, 3251-3259.

13\) Bugge, T. H., Flick, M. J., Daugherty, C. C., and Degen, J. L.
(1995). Plasminogen deficiency causes severe thrombosis but is
compatible with development and reproduction. *Genes & Dev.*, **9**,
794-807.

14\) Bugge, T. H., Suh, T. T., Flick, M. J., Daugherty, C. C., Rømer,
J., Solberg, H., Ellis, V., Danø, K., and Degen, J. L. (1995). The
receptor for urokinase-type plasminogen activator is not essential for
mouse development or fertility. *J. Biol. Chem.,* **270**, 16886-16894.

15\) Rømer, J., Bugge, T. H., Pyke, C., Lund, L. R., Flick, M. J.,
Degen, J. L., and Danø, K. (1996). Impaired wound healing in mice with a
disrupted plasminogen gene. *Nature Medicine,* **2**, 287-292.

16\) Rømer, J., Bugge, T. H., Pyke, C., Lund, L. R., Flick, M. J.,
Degen, J. L., and Danø, K. (1996). Plasminogen and wound healing (Letter
to the editor). *Nature Medicine,* **2**, 725.

17\) Bugge, T. H., Flick, M. J., Danton M. J., Daugherty, C. C., Rømer,
J., Danø, K., Carmeliet, P., Collen, D., and Degen J. L. (1996).
Urokinase-type plasminogen activator is effective in fibrin clearance in
the absence of its receptor or tissue-type plasminogen activator. *Proc.
Natl. Acad. Sci. (USA),* **93**, 5899-5904.

18\) Bugge, T. H., Xiao, Q., Kombrinck, K. W., Flick, M. J., Holmbäck,
K., Danton, M. J., Colbert, M. C., Witte, D. P., Fujikawa, K., Davie, E.
W., and Degen, J. L. (1996). Fatal embryonic bleeding events in mice
lacking tissue factor, the cell-associated initiator of blood
coagulation. *Proc. Natl. Acad. Sci. (USA),* **93**, 6258-6263.

19\) Bugge, T. H., Kombrinck, K., Flick, M. J., Daugherty, C. C.,
Danton, M. J., and Degen J. L. (1996). Loss of fibrinogen rescues mice
from the pleiotropic effects of plasminogen deficiency. *Cell,* **87**,
709-719.

20\) Tsirka, S. E., Rogove, A. D., Bugge, T. H., Degen, J. L., and
Strickland, S. (1997). An extracellular proteolytic cascade promotes
neuronal degeneration in the mouse hippocampus. *J. Neurosci.,* **17**,
543-552.

21\) Coleman, J. L., Gebbia, J. A., Piesman, J., Degen, J. L., Bugge, T.
H., and Benach, J. L. (1997). Plasminogen is required for efficient
dissemination of *Borrelia burgdorferi* in ticks and for enhancement of
spirochetemia in the vertebrate host. *Cell,* **89**, 1111-1119.

22\) Tsirka, S. E., Bugge, T. H., Degen, J. L., and Strickland, S.
(1997). Neuronal death in the central nervous system demonstrates a
non-fibrin substrate for plasmin. *Proc. Natl. Acad. Sci. (USA),*
**94**, 9779-9781*.*

23\) Xiao, Q., Danton, M. J., Witte, D. P., Kowala, M. C., Valentine, M.
T., Bugge, T. H., and Degen, J. L. (1997). Plasminogen-deficiency
accelerates vessel wall disease in mice predisposed to atherosclerosis.
*Proc. Natl. Acad. Sci. (USA),* **94**, 10335-10340*.*

24\) Bugge, T. H., Kombrinck, K. W., Xiao, Q., Holmbäck, K., Daugherty,
C. C., Witte, D. P., and Degen, J. L. (1997). Growth and dissemination
of Lewis lung carcinoma in plasminogen-deficient mice. *Blood,* **90**,
4522-4531.

25\) Kao, W.-Y., Kao, C. W., Kaufman, A. H., Kombrinck, K. W., Converse,
R. L., Good, W. V., Bugge, T. H., and Degen, J. L. (1998). Healing of
corneal epithelial defects in plasminogen and fibrinogen-deficient mice.
*Investigative Ophthalmology & Visual Science,* **39**, 502-508.

26\) Drew, A. F., Kaufman, A. H., Kombrinck, K. W., Danton, M. J.,
Daugherty, C. C., Degen, J. L., and Bugge, T. H. (1998). Ligneous
conjunctivitis in plasminogen-deficient mice. *Blood,* **91**,
1616-1624.

27\) Bugge, T. H., Lund, L. R., Kombrinck, K. W., Nielsen, B. S.,
Holmbäck, K., Drew, A. F., Flick, M. J., Witte, D. P., Danø, K. and
Degen, J. L. (1998). Reduced metastasis of Polyoma virus middle T
antigen-induced mammary cancer in plasminogen-deficient mice.
*Oncogene,* **16**, 3097-3104*.*

28\) Sun, Y. W., Witte, D. P., Degen, J. L., Colbert, M. C., Burkart, M.
C., Holmbäck, K., Xiao, Q., Bugge, T. H., and Degen, S. J. (1998).
Prothrombin deficiency results in embryonic and neonatal lethality in
mice. *Proc. Natl. Acad. Sci. (USA),* **95**, 7597-7602.

29\) Busso, N., Péclat, V., Van Ness, K., Kolodziesczyk, E., Degen, J.
L., Bugge, T., and So, A. (1998). Exacerbation of antigen-induced
arthritis in urokinase-deficient mice*. J. Clin. Invest.,* **102**,
41-50.

30\) Bugge, T. H., and Degen, J. L. (1998). Plg. In *The Gene Knockout
FactsBook.* (eds. Mak, T. W., Penninger, J., Roder, J., Rossant, J., and
Sounders, M.), Academic Press, San Diego, CA. p876-877.

31\) Bugge, T. H., and Degen, J. L. (1998). uPAR. In *The Gene Knockout
FactsBook.* (eds. Mak, T. W., Penninger, J., Roder, J., Rossant, J., and
Sounders, M.), Academic Press, San Diego, CA p1061-1062*.*

32\) Bugge, T. H., and Degen, J. L. (1998). Tissue factor. In *The Gene
Knockout FactsBook.* (eds. Mak, T. W., Penninger, J., Roder, J.,
Rossant, J., and Sounders, M.), Academic Press, San Diego, CA
p1010-1011.

33\) Gebbia, J. A., Monco, J. C., Degen, J. L., Bugge, T. H., and
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34\) Chen, Z.L, Indyk, J. A., Bugge, T. H., Kombrinck, K. W., Degen, J.
L., and Strickland, S. (1999). Neuronal death and blood-brain barrier
breakdown after excitotoxic injury are independent processes. *J.
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35\) Lund, L. R., Rømer, J., Bugge, T. H., Nielsen, B. S., Frandsen, T.
L., Degen, J. L., Stephens, R. W., and Danø, K. (1999). Functional
overlap between two classes of matrix-degrading proteases in wound
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36\) Bezerra, J. A., Bugge, T. H., Melin-Aldana, H., Sabla, G.,
Kombrinck, K. W., Witte, D. P., and Degen, J. L. (1999). Plasminogen
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37\) List, K., Jensen, O. N., Bugge, T. H., Lund, L. R., Ploug, M.,
Danø, K., and Behrendt, N. (2000). Plasminogen-independent initiation of
the pro-uPA activation cascade *in vivo*. Activation of pro-urokinase by
glandular kallikrein (mGK-6) in plasminogen-deficient mice.
*Biochemistry,* **39**, 508-515*.*

38\) Drew, A. F., Schiman, H. L., Kombrinck, K. W., Bugge, T. H., Degen,
J. L., and Kaufman, A. H. (2000). Persistent corneal haze after excimer
laser photokeratectomy in plasminogen-deficient mice. *Invest.
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39\) Wu, Y. P., Siao, C. J., Lu, W., Sung, T. C., Frohman, M. A., Milev,
P., Bugge, T. H., Degen, J. L., Levine, J. M., Margolis, R. U., and
Tsirka, S. E. (2000). The tissue plasminogen activator (tPA)/plasmin
extracellular proteolytic system regulates seizure-induced hippocampal
mossy fiber outgrowth through a proteoglycan substrate. *J. Cell Biol.,*
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40\) Lund, L. R., Bjørn, S. F., Sternlicht, M. D., Nielsen, B. S.,
Solberg, H., Usher, P. A., Østerby, R., Christensen, I. J., Stephens, R.
J., Bugge, T. H., Danø, K., and Werb, Z. (2000). Lactational competence
and involution of the mouse mammary gland require plasminogen.
*Development,* **127**, 4481-4492.

41\) Goguen, J. D., Bugge, T., and Degen, J. L. (2000). Role of the
pleiotropic effects of plasminogen deficiency in infection experiments
with plasminogen-deficient Mice. *Methods*, **21**, 179-183.

42\) Drew, A. F., Tucker, H. L., Kombrinck, K. W., Simon, D. I., Bugge,
T. H., and Degen, J. L. (2000). Plasminogen is a critical determinant of
vascular remodeling in mice. *Circulation Research*, **87**, 133-139.

43\) Palumbo, J. S., Kombrinck, K. W., Drew, A. F., Grimes, T. S.,
Kiser, J. H., Degen, J. L., and Bugge, T. H. (2000). Fibrinogen is an
important determinant of the metastatic potential of circulating tumor
cells. *Blood,* **96**, 3302-3309.

44\) Bezerra, J. A., Currier, A. R., Melin-Aldana, H., Sabla, G., Bugge,
T. H., Kombrinck, K. W., and Degen, J. L. (2001). Plasminogen Activators
Direct Reorganization of the Liver Lobule after Acute Injury. *Am. J.
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45\) Liu, S., Bugge, T. H., and Leppla, S. H. (2001). Targeting tumor
cells by urokinase plasminogen activator-activated anthrax toxin
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46\) Engelholm, L. H., Nielsen, B. S., Netzel-Arnett, S., Solberg, H.,
Chen, X. D., Lopez Garcia J.M., Lopez-Otin, C., Young, M. F.,
Birkedal-Hansen, H., Danø, K., Lund, L. R., Behrendt, N., and Bugge, T.
H. (2001). The urokinase plasminogen activator receptor-associated
protein/Endo 180 is coexpressed with its interaction partners uPAR and
matrix metalloproteinase-13 during osteogenesis. *Lab. Invest.* **81**,
1403-1414.

47\) Yepes, M., Sandkvist, M., Coleman, T. A., Moore, E., Wu, J.-Y.,
Mitola, D., Bugge, T. H., and Lawrence, D. (2002). Regulation of seizure
spreading by neuroserpin and tissue plasminogen activator is
plasminogen-independent. *J.Clin. Invest.* **109**, 1571-1578.

48\) Bugge, T. H. (2002). Proteolysis in carcinogenesis. In "Head and
Neck Cancers", *Eds.* Gutkind, J. S., Jacobs J. R., and Lippman, S. M.,
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49\) Frankel. A. E., Bugge, T. H., Liu, S., Vallera, D. A., and Leppla,
S. H. (2002). Peptide toxins directed at matrix dissolution systems of
cancer cells. *Protein and Peptide Lett*., **9**, 1-14.

50\) List, K., Haudenschild, C. C., Szabo, R., Chen, W., Wahl, S. M.,
Swaim, W., Engelholm, L. H., Behrendt, N., and Bugge, T. H. (2002).
Matriptase/MT-SP1 is required for postnatal survival, epidermal barrier
function, hair follicle development, and thymic homeostasis. *Oncogene*,
**21**, 3765-3779.

51\) Bannach, F. G., Gutierrez, A., Fowler, B. J., Bugge, T. H., Degen,
J. L., Parmer, R. J., and Miles, L. A. (2002). Localization of
regulatory elements mediating constitutive and cytokine-stimulated
plasminogen gene expression. *J. Biol. Chem.* **277**, 38579-38588.

52\) Netzel-Arnett, S. A., Mitola, D. J., Yamada, S., Chrysovergis, K.,
Holmbeck, K., Birkedal-Hansen, H. and Bugge, T. H. (2002). Collagen
Dissolution by Keratinocytes Requires Cell Surface Plasminogen
Activation and Matrix Metalloproteinase Activity. *J. Biol. Chem.*,
**277**, 45154-45161.

53\) Curino, A., Mitola, D., Aaronson H., McMahon, G., Raja, K., Keegan,
A., Lawrence, D. A, and Bugge, T. H. (2002). Plasminogen promotes
sarcoma growth and suppresses the accumulation of tumor-infiltrating
macrophages. *Oncogene*, **21**, 8830-8842.

54\) Montaner, S., Sodhi, A., Molinolo, A., Bugge, T. H., Sawai, E. T.,
He, Y., Li, Y., Ray, P. E., and Gutkind, J. S. (2003). Endothelial
infection with KSHV genes in vivo reveals that vGPCR initiates Kaposi\'s
sarcomagenesis and can promote the tumorigenic potential of viral latent
genes. *Cancer Cell*, 3, 23-36.

55\) Liu, S., Aaronson, H., Mitola, D., Leppla, S. H., and Bugge, T. H.
(2003). Potent anti-tumor activity of a urokinase-activated engineered
anthrax toxin. *Proc. Natl. Acad. Sci. (USA)*, **100**, 657-662.

56\) Netzel-Arnett, S., Hooper, J. D., Szabo, R., Madison, E. L.,
Quigley, J. P., Bugge, T. H. and Antalis, T. M. (2003). Membrane
Anchored Serine Proteases: An emerging class of cell surface proteolytic
enzymes with potential roles in cancer. *Cancer and Metastasis Reviews*,
**22**, 237-258.

57\) Engelholm, L. H., List, K., Netzel-Arnett, S., Cukierman, E.,
Mitola, D. J., Aaronson, H., Kjøller, L., Larsen, J. K., Yamada, K. M.,
Strickland, D. S., Holmback, K., Danø, K., Birkedal-Hansen, H.,
Behrendt, N., and Bugge T. H. (2003). uPARAP/Endo180 is essential for
cellular uptake of collagen and promotes fibroblast collagen adhesion.
*J. Cell Biol.*, **160**, 1009-1015.

58\) Pedersen, T. X., Leethanakul, C, Patel V, Mitola, D. J., Lund,
L.R., Danø, K., Johnsen, M., Gutkind, J. S., and Bugge, T. H. (2003).
Laser capture microdissection-based *in vivo* genomic profiling of wound
keratinocytes identifies similarities and differences to squamous cell
carcinoma. *Oncogene*, **22**, 3964-3976.

59\) Szabo, R., Qingyu Wu, Q., Dickson, R. B., Netzel-Arnett, S,
Antalis, T. M., and Bugge, T. H. (2003). Type II Transmembrane Serine
Proteases. *Thrombosis and Haemostasis*, **90**, 185-193.

60\) Liu, S. Schubert, R. L. Bugge, T. H., and Leppla, S. H. (2003).
Anthrax toxin: structures, functions, and tumor targeting. *Expert Opin.
Biol. Ther.*, **3**, 843-853.

# 

### 61) Makarova, A., Mikhailenko, I, Bugge, T. H., List, K. Lawrence, D, and Strickland, D. K. (2003). The LDL receptor-related protein modulates protease activity in the brain by mediating the cellular internalization of both neuroserpin and neuroserpin:tPA complexes. *J. Biol. Chem.*, 278, 50250-50258.

### 

### 62) Frankel, A. F., Neville, D. M., Bugge, T.H., Kreitman, R. J., Leppla, S. H. (2003) Immunotoxin therapy of hematologic malignancies. *Semin Oncol.*, 30, 545-557. 

63\) Yepes, M., Sandkvist, M., Moore, E., Bugge, T.H., Strickland, D.
K., and Lawrence, D. (2003). Tissue-type plasminogen activator opens the
blood brain barrier via the low density lipoprotein receptor. *J. Clin.
Invest.,* **112**, 1533-1540.

# 64) List, K., Szabo, R., Wertz, P.W., Segre, J., Haudenschild, C. C., Kim, S.-Y., and Bugge, T. H. (2003). Loss of proteolytically processed filaggrin caused by epidermal deletion of Matriptase/MT-SP1. *J. Cell Biol.*, 163, 901-910*.*

# 65) Riedlinger, G., Kridel, S., Al-Housseini, A.,Gardner, L., Bugge, T. H., Leppla, S. H., Duesbery, N., Vande Woude, G., and Frankel, A. (2003). Metastatic melanoma and matrix metalloproteases. *Drugs of the Future*, 28, 897-904.

66\) Kjøller, L., Engelholm, L., Høyer-Hansen, M., Danø, K., Bugge, T.
H., and Behrendt, N. (2004). uPARAP/endo180 directs lysosomal delivery
and degradation of collagen. *Exp. Cell. Res*., **293***,* 106-116.

67\) Law, B., Curino, A., Bugge, T.H., Weissleder, R., and Tung, C. H.
(2004). Design, synthesis and characterization of urokinase-type
plasminogen activator sensitive near-infrared reporter. *Chem. Biology*,
**11**, 99-106*.*

68\) Abi-Habib, R. J., Liu, S., Bugge, T. H., Leppla, S., H., and
Frankel, A. E. (2004). Urokinase activated recombinant diphtheria toxin
targeting the granulocyte-macrophage colony-stimulating factor receptor
(dtu2gmcsf) is selectively cytotoxic to human acute myeloid leukemia
blasts. *Blood,* **104**, 2143-2148.

69\) Curino, A., Patel, V., Nielsen, B. S., Iskander, I. J., Ensley, J.
F.^,^ Yoo, G. H., Holsinger, F. C., Myers, J. N., El-Nagaar, A.,
Kellman, R, Shillitoe, E. J., Molinolo, A. A., Gutkind, J. S., and
Bugge, T. H. (2004) Detection of uPA activity in oral cancer by laser
capture microdissection combined with plasminogen-casein zymography.
*Oral Oncology,* **40**, 1026-1032*.*

70**)** Hobson, J. P., Netzel-Arnett, S., Szabo, R., Rehault, S. M.,
Church F. C., Strickland, D. K., Lawrence, D. A., Antalis, T. M. and
Bugge, T. H. (2004) Mouse *DESC1* is located within a cluster of seven
*DESC1*-like genes and encodes a type II transmembrane serine protease
that forms serpin inhibitory complexes**.** *J. Biol. Chem.,***279**,
46981-46994*.*

71\) Law, B., Hsiao, J.-K., Bugge, T. H., Weissleder, R., Tung, C.-H.
(2004). Novel optical zymography for the detection of urokinase
plasminogen activator in biological samples, *Analytical Biochemistry*,
**338**, 151-158.

72\) Westcott. M. M., Abi-Habib, R., Cohen, K., Willingham, M., Vallera,
D., Liu, S., Bugge, T. H., Leppla, S. H., and Frankel, R. (2004).
Diphtheria toxin-murine GMCSF-induced hepatotoxicity is mediated by
Kupffer cells. *Mol. Cancer Ther.,* **3**,1681-1689.

73\) Antalis, T.M., Bugge, T.H., Lawrence, D. A., Netzel-Arnett, S.,
Schwartz, B. S., Strickland, D. K. (2005). Amalfi to Washington D.C. -
Twenty Years of Plasminogen Activator Research. *Thrombosis and
Haemostasis*, **93**, 625-626*.*

## 

74\) Szabo, R., Netzel-Arnett, S., Hobson, J. P., Antalis, T. M., and
Bugge, T. H., (2005). Matriptase-3 is a novel phylogenetically preserved
membrane-anchored serine protease with broad serpin reactivity.
*Biochemistry*, **390**, 231-242.

## 75) Liu, S., Redeye, V., Kuremsky, J. G., Bugge, T. H., and Leppla, S. H. (2004). Intermolecular complementation achieves high-specificity tumor targeting by anthrax toxin. *Nature Biotechnology*, 23, 725-730.

76\) Curino, A. C., Nielsen, B. S., Engelholm, L. H., Molinolo, A. A.,
Behrendt, N., and Bugge, T. H. (2005). Intracellular collagen
degradation mediated by uPARAP/Endo180 is a major pathway of
extracellular matrix turnover during malignancy. *J. Cell Biol.*
**169**, 977-986.

77\) List, K., Szabo, R., Molinolo, A., Sriuranpong, V., Redeye, V.,
Burke B., Murdock, T., Nielsen, B.S., Gutkind, J.S., and Bugge, T. H.
(2005). Deregulated matriptase proteolysis causes *ras*-independent
multistage carcinogenesis and promotes *ras*-mediated malignant
transformation. *Genes & Dev.*, 19, 1934-1950.

78\) Filippov, S., Chun, T.-H., Hotary, K. B., Ota, I., Allen, E. D.,
Bugge, T.H., Birkedal-Hansen, H., Holmbeck, K., Fay, W., and Weiss, S.J.
(2005). MT1-MMP deficiency suppresses vascular neointimal lesion
formation. *J. Exp. Med*, **202**, 663-671.

79\) Rønø, B., Rømer^,^ J., Liu, S., Bugge, T. H., Leppla, S. H., and
Kristjansen, P. E. (2005). Significant antitumor efficacy after systemic
administration of urokinase activation-dependent anthrax toxin.
*Molecular Cancer Therapeutics*, **5**, 89-96*.*

80\) Bugge, T.H. and Leppla, S. H. (2006) Anthrax target in macrophages
pinpointed. *Nature Genetics*, **38**, 137-138*.*

81\) List, K., Szabo, S., Molinolo, A., Nielsen, B. S., and Bugge, T. H.
(2006). Delineation of matriptase protein expression by enzymatic gene
trapping suggests diverging roles in barrier function, hair formation,
and squamous cell carcinogenesis. *Am. J. Pathol*., **168**, 1513-1525.

82\) Hobson, J. P., Liu S., Rønø, B., Leppla, S. H., and Bugge, T.H.
(2006). Imaging specific cell surface proteolytic activity in single
living cells. *Nature Methods*, **3**, 259 -- 261.

83\) List, K., Bugge, T. H., and Szabo (2006). Matriptase: Potent
proteolysis of the cell surface. *In press, Molecular Medicine.*

84\) Szabo, R., Molinolo, A., List, K., and Bugge, T. H. (2006).
Matriptase is the essential target of hepatocyte growth factor activator
inhibitor-1 during embryonic development. *In press, Oncogene.*

85\) Abi-Habib, R. J., Singh, R., Liu^,^ S., Bugge, T. H., Leppla^,^ S.
H., and Frankel, A. E. (2006). A Urokinase Activated Recombinant Anthrax
Toxin Is Selectively Cytotoxic to Many Different Tumors. *In press,
Molecular Cancer Therapeutics*.

86\) Schwartz, D. R., Moin, K., Yao, B, Matrisian, L. M, Coussens^,^ L.
M., Bugge, T. H., Fingleton, B., Acuff, H. B., Sinnamonm M., Nassar, H.
Krawetz^,^ B., Linebaugh^,^ B., and Sloane, B. F. (2006). The Hu/Mu
ProtIn oligonucleotide microarray: application of a custom dual species
array for mining protease, protease inhibitor and protease interactor
gene expression in tumors and their microenvironment. *Submitted.*

87\) Netzel-Arnett S., Currie, B. M., Szabo, R., Lin, C. Y., Chen, L M.,
Chai K. X., Antalis, T. M., Bugge, T. H., and List, K. (2006) Evidence
for a matriptase-prostasin proteolytic cascade regulating terminal
epidermal differentiation. *In Press, J. Biol. Chem.*