Athan Kuliopulos, MD, PhD Page XXX of 5
Curriculum Vitae
Athan Kuliopulos, M.D., Ph.D.
Professor of Medicine and Biochemistry
Director of the Hemostasis and Thrombosis Laboratory
Tufts Medical Center
Box 7510
850 Washington Street
Boston, Massachusetts 02111, USA
Telephone: (617) 636-8482 FAX: (617) 636-7855
E-mail:
website: http://www.tufts-mori.org/hemostasis/research.asp
Education
Undergraduate
1983 B. S., Biology Rensselaer Polytechnic Institute, Troy, NY
Medical School and/or Graduate School
1989 Ph. D., Biochemistry, Cellular, Johns Hopkins Medical School, Baltimore, MD
and Molecular Biology
1989 M.D. Johns Hopkins Medical School
Postdoctoral Training
Fellowships
1990 Blood Coagulation Harvard Medical School
(Judith Graham Pool
Fellow, National
Hemophilia Foundation)
Positions
1994-2002 Assistant Professor of Medicine, Division of Hematology-Oncology,
Tufts University School of Medicine
1994-2002 Assistant Professor of Biochemistry, Tufts University School of Medicine
1995-present Faculty Member, Sackler School of Biomedical Sciences, Tufts University School of Medicine
1998-2003 Investigator, Molecular Cardiology Research Institute, Tufts-New England Medical Center
1998-present Director of the Hemostasis and Thrombosis Laboratory, Tufts Medical Center
2002-2010 Associate Professor of Medicine, Tufts University School of Medicine
2002-2010 Associate Professor of Biochemistry, Tufts University School of Medicine
2002-present Faculty member in the Genetics Program, Tufts University School of Medicine
2010-present Professor of Medicine, Tufts University School of Medicine
2010-present Professor of Biochemistry, Tufts University School of Medicine
Honors and Service
1983-1989 Trainee of the Medical Scientist Training Program (MSTP), National Institutes of Health
1989 Paul Ehrlich Award for Basic Science Research, Johns Hopkins Medical School
1991-1993 Judith Graham Pool Postdoctoral Fellowship, National Hemophilia Foundation
1993-1994 NRSA, National Institutes of Health
1996-1998 American Society of Hematology Scholar Award
1996-2000 Pew Scholar Award in the Biomedical Sciences
2002-present Ad Hoc Member of HT study section, special emphasis panels (ZG), PPG reviews
2002-present Member, Tufts Medical Center Research Fund Grant Committee,
2002-present Member, Tufts MD-PhD Admissions Committee
2006 TechConnect Emerging Technology Award, First Place (Life Sciences) for Pepducin technology
2006 Elected to the Johns Hopkins University Society of Scholars
2007-present Founder, Chair-Scientific Advisory Board, Anchor Therapeutics, Cambridge, MA
2007 Member, ZG-HT Program Project Grant Panel, NIH
2009 Chair and Co-Organizer of 1st Pepducin Science Symposium, Cambridge, MA
2010 Chair and Co-Organizer of 2nd Pepducin Science Symposium, Cambridge, MA
2010 Elected to the Association of American Physicians
2011 Member, Translational Research Centers in Thrombotic and Hemostatic Disorders (ZHL1) Grant Panel Study Section, NIH
Bibliography (Peer-reviewed papers):
20. Covic, L., Gresser, A. L., & Kuliopulos, A. (2000) Biochemistry 39, 5458-5467. Biphasic Kinetics of Activation and Signaling for PAR1 and PAR4 Thrombin Receptors in Platelets. PMID: 10820018
21. Santos, B. F., Serrano, S. M. T., Kuliopulos, A., & Niewiarowski, S. (2000) FEBS Letters 477, 199-202. Interaction of Viper venom Serine Peptidases with Thrombin Receptors on Human Platelets. PMID: 10908720
22. Jacques, S., LeMasurier, M., Sheridan, P. J., Seeley, S. K. & Kuliopulos, A. (2000) J. Biol. Chem. 275, 40671-40678. Substrate-Assisted Catalysis of the PAR1 Thrombin Receptor: Enhancement of Macromolecular Association and Cleavage. PMID: 11005807
23. Andrabi, S. A., Azam, M., Kamath, L., Sahr, K. E., Kuliopulos, A., & Chishti, A. H. (2001) Mol. Cell. Biol. 21, 2213-2220. Disruption of the Mouse m-Calpain Gene reveals an Essential Role in Platelet Function. PMID: 11238954
24. Kamath, L., Meydani, A., Foss, F., & Kuliopulos, A. (2001) Cancer Research 61, 5933-5940. Signaling From Protease-Activated Receptor-1 Inhibits Migration and Invasion of Breast Cancer Cells. PMID: 11479236
25. Covic, L., Gresser, A. L., Talavera, J., Swift, S., & Kuliopulos, A. (2002) Proc. Natl. Acad. Sci. USA 99, 643-648. Activation and Inhibition of G Protein-coupled Receptors by Cell-Penetrating, Membrane-Tethered Peptides. PMID: 11805322
26. Covic, L., Singh, C., Smith, H., & Kuliopulos, A. (2002) Thrombosis and Haemostasis 87, 722-727. Role of the PAR4 thrombin receptor in stabilizing platelet-platelet aggregates as revealed by a patient with Hermansky-Pudlak Syndrome. PMID: 12008957
27. Covic, L., Misra, M., Badar, J., Singh, C., & Kuliopulos, A. (2002) Nature Medicine 8, 1161-1165. Pepducin-Based Intervention of Thrombin Receptor Signaling and Systemic Platelet Activation. PMID: 12357249
28. Seeley, S., Covic, L., S. J. Jacques, Sudmeier, J., Baleja, J. and Kuliopulos, A. (2003) Chem. and Biol. 10, 1033-1041. Structural Basis for Thrombin activation of a Tethered Ligand Receptor: Inhibition of Intramolecular Liganding. PMID: 14652070
29. Jacques, S. & Kuliopulos, A. (2003) Biochem. J. 376, 733-740. Protease-activated receptor-4 uses dual prolines and an anionic retention motif for thrombin recognition and cleavage. PMID: 13678420
30. Kuliopulos, A., Mohanlal, R., Covic, L. (2004) Thromb. Haemost. 92, 1387-1393. Effect of selective inhibition of the p38 MAP kinase pathway on platelet aggregation. PMID: 15583748
31. Boire, A., Covic, L., Agarwal A., Jacques, S., Sherifi S. and Kuliopulos, A. (2005) Cell 120, 303-313. PAR1 is a Matrix Metalloprotease-1 Receptor that Promotes Invasion and Tumorigenesis of Breast Cancer Cells. PMID: 1570789
32. Kimmelstiel, C., Badar, J., Covic, L., Waxman, S., Weintraub, A., Jacques, S. & Kuliopulos, A. (2005) Thromb. Research 116, 55-66. Pharmacodynamics and pharmacokinetics of the platelet GPIIb/IIIa inhibitor tirofiban in patients undergoing percutaneous coronary intervention: implications for adjustment of tirofiban and clopidogrel dosage. PMID: 15850609
33. Kaneider, N. C., Agarwal, A., Leger, A. & Kuliopulos, A. (2005) Nature Medicine 11, 661-665. Reversing Systemic Inflammatory Response Syndrome with Chemokine Receptor Pepducins. PMID: 1588011
34. Swift, S., Leger, A., Talavera, J., Zhang, L., Bohm, A., and Kuliopulos, A. (2006) J. Biol. Chem. 281, 4109-4116. Role of the PAR1 Receptor 8th Helix in Signaling: the 7-8-1 Receptor Activation Mechanism. PMID: 16354660
35. Leger, A. J., Jacques, S. L., Badar, J., Kaneider, N. C., Derian, C. K., Andrade-Gordon, P., Covic, L. and Kuliopulos, A. (2006) Circulation 113, 1244-54. Blocking the Protease-Activated Receptor 1-4 Heterodimer in Platelet-Mediated Thrombosis. PMID: 1650517
36. Nguyen, N., Kuliopulos, A., Graham, R. A. & Covic, C. (2006) Cancer Research 66, 2658-65. Tumor-derived Cyr61 promotes stromal matrix metalloprotease-1 production and PAR1-dependent migration of breast cancer cells. PMID: 16510585
37. Leger, A. J., Covic, L. & Kuliopulos, A. (2006) Circulation 114, 1070-1077. Protease-Activated Receptors in Cardiovascular Diseases. PMID: 16952995
38. Kaneider, N. C., Leger, A. J. & Kuliopulos, A. (2006) FEBS J. 273, 4416-4424. Therapeutic Targeting of Molecules involved in Leukocyte-Endothelial Cell Interactions. PMID: 16956369
39. Kaneider, N. C., Leger, A. J., Agarwal, A., Nguyen, N., Perides, G., Derian, C., Covic, L. & Kuliopulos, A. (2007) Nature Immunology 8, 1303-1312. Role reversal for the receptor PAR1 in sepsis-induced vascular damage. PMID: 17965715
40. Agarwal, A., Covic, L., Sevigny, L. M., Kaneider, N. C., Lazarides, K., Azabdaftari, G., Sharifi S., and Kuliopulos, A. (2008) Mol Can Therap 7:2746-57. Targeting a Metalloprotease-PAR1 Signaling System with Cell-Penetrating Pepducins Inhibits Angiogenesis, Ascites and Progression of Ovarian Cancer. PMID: 1879075
41. Smyth, S.S., Woulfe, D.S., Weitz, J.I., Gachet, C., Conley, P.B., Goodman, S.G., Roe, M.T., Kuliopulos, A., Moliterno, D.J., French, P.A., Steinhubl, S.R., Becker, R.C. (2008) Arterio Thromb Vasc Biol 29:449-457. G-Protein–Coupled Receptors as Signaling Targets for Antiplatelet Therapy. PMID: 19023091
42. Trivedi, V., Boire, A., Tchernychev, B., Kaneider, N.C., Leger, A.J., O’Callaghan, K., Covic, L. & Kuliopulos, A. (2009) Cell 137:332-343. Platelet Matrix Metalloprotease-1 Mediates Thrombogenesis by Activating PAR1 at a Cryptic Ligand Site. PMID: 19379698
43. Yang, E., Boire, A., Agarwal, A., Nguyen, N., Kuliopulos, A., and Covic, L. (2009) Cancer Research 69:6223-31. Blockade of metalloprotease-PAR1 signaling with cell-penetrating pepducins inhibits Akt-survival pathways in breast cancer and accelerates tumor death. PMID: 19622769
44. Miller, J., Agarwal, A., Devi, L.A., Fontanini, K., Hamilton, J.A., Pin, J.-J., Shields, D.C., Spek, C.A., Sakmar, T.P., Kuliopulos, A., Hunt, S.W. (2009) Ann. N.Y. Acad. Sci. 1180: E1-E12. Insider access: pepducin symposium explores a new approach to GPCR modulation. PMID: 1992563
45. Swift, S., Xu, J., Trivedi, V., Austin, K.M., Tressel, S.L., Zhang, L., Covic, L., Kuliopulos, A. (2010) J Biol Chem 285:11402-10 A Novel PAR1-Interactor, Bicaudal-D1, Regulates G protein Signaling and Internalization. PMID: 20164183
46. Agarwal, A., Tressel, S. L., Kaimal, R., Balla, M., Lam, F.H., Covic, L, Kuliopulos, A. (2010) Cancer Research 70: 5880-90. Identification of a metalloprotease-chemokine signaling system in the ovarian cancer microenvironment: implications for anti-angiogenic therapy. PMID: 20570895
47. Kimmelstiel, C*., Zhang, P*., Kapur, N.K., Weintraub, A., Krishnamurthy, B., Castaneda, V., Covic, L., & Kuliopulos, A. (2011) Circ Cardiovasc Interv 4:171-9. Bivalirudin is a Dual Inhibitor of Thrombin and Collagen-Dependent Platelet Activation in Patients Undergoing Percutaneous Coronary Intervention. *equal contributors. PMID: 21364148
48. Dowal, L., Sim, D., Dilks, J.R., Blair, P., Beaudry, S., Denker, B., Koukos, G., Kuliopulos, A., Flaumenhaft, R., (2011) Proc. Natl. Acad. Sci. USA 108: 2951-6. Identification of an antithrombotic allosteric modulator that acts through helix 8 of PAR1. PMID: 21282664, PMC3041116
49. Cisowki, J., Yang, J., Kuliopulos, A., Nguyen, N., Deng, Q., Yang, E., Agarwal, A., Hunt, S., McMurry, T., Brinkerhoff, L., & Covic, L. (2011) Am J Pathol 179:513-23. Novel Targeting of Protease-activated receptor-1 in advanced non-small cell lung cancer. PMID: 21703428
50. Tressel, S.L., Kaneider, N.C., Kasuda, S., Foley, C., Koukos, G., Austin, K.M., Agarwal, A., Covic, L. Opal, S. & Kuliopulos, A. (2011) EMBO Mol Med 3:370-84. A matrix metalloprotease-PAR1 system regulates vascular integrity, systemic inflammation and death in sepsis. PMID: 21591259
51. Sevigny, L.M., Zhang, P., Bohm, A., Lazarides, K., Perides, G., Covic, L., Kuliopulos, A. (2011) Proc. Natl. Acad. Sci. USA 108: 8491-6. Interdicting PAR2-driven inflammation with cell-penetrating pepducins. PMID: 21536878
52. Koukos, G., Sevigny, L.M., Zhang, P., Covic, L., & Kuliopulos, A. (2011) Serine and Metalloprotease Signaling Through PAR1 in Arterial Thrombosis and Vascular Injury. IUBMB Life 63:412-8. PMID: 21557445
53. Dimond, P., Carlson, K., Bouvier, M., Gerard, C., Xu, L., Covic, L., Agarwal, A., Ernst, O., Janz, J., Schwartz, W.T., Gardella, T.J., Milligan, G., Kuliopulos, A., Sakmar T.P., Hunt, S. (2011) Ann N Y Acad Sci 1226:34-39. GPCR Modulation with Pepducins: Moving Closer to the Clinic. PMID: 21615752
54. Hatziapostolou, M., Koukos, G., Polytarchou, C., Serebrennikova, O., Kuliopulos, A,. Tsichlis, P.N. (2011) Science Sig 4: 1-12. Tumor progression locus 2 mediates signal-induced increases in cytoplasmic calcium and cell migration.
55. Tressel, S. L., Koukos, G., Tchernychev, B., Jacques, S. L., Covic, L. & Kuliopulos, A. (2011) Methods Mol Biol, 683:259-75. Pharmacology, Biodistribution, and Efficacy of GPCR-based Pepducins in Disease Models. PMID: 21053136
56. Sevigny LM, Austin KM, Zhang P, Kasuda S, Koukos G, Sharifi S, Covic L, Kuliopulos A. Arterioscler Thromb Vasc Biol. 2011 Sep 22. [Epub ahead of print]. Protease-Activated Receptor-2 Modulates Protease-Activated Receptor-1-Driven Neointimal Hyperplasia. PMID: 21940952
57. O’Callaghan, K., Kuliopulos, A., Covic, L. (2011) J Biol Chem (in press). Turning Receptors On and Off with Intracellular Pepducins: New Insights into G-protein Coupled Receptor Drug Development.
58. O’Callaghan, K., Lee, L., Nguyen, N., Hsieh, M.-Y., Kaneider, N.C., Klein, A.K., Sprague, K., Van Etten, R.A., Covic, L.* & Kuliopulos, A.* (2011) (under review). Targeting CXCR4 with cell-penetrating pepducins in lymphoma and lymphoblastic leukemia.
Invited Papers:
1. Kuliopulos, A., Covic, L. (2003) Life Sci. 74, 255-262. Blocking Receptors from the Inside. DOI: 10.1016/j.lfs.2003.09.012
2. Covic, L., Tchernychev, B., Jacques, S., & Kuliopulos, A. (2007) Handbook of Cell-Penetrating Peptides (Taylor & Francis, NY) 245-257. Pharmacology and in vivo efficacy of pepducins in hemostasis and arterial thrombosis. ISBN:9780849350900
3. Zhang, P., Covic, L., & Kuliopulos, A. (2012) Chapter 13: Protease-Activated Receptors. Platelets 3rd Ed. (Elsevier, PA)
Invited Lectures and Chairs (last 3 years only):
January 28, 2009 Division Hematology-Oncology, Tufts Medical Center
(CME accredited lecture)
March 8-9, 2009 Keynote Address, 1st Pepducin Science Symposium, Cambridge, MA
Chair and Co-Meeting Organizer
June 7-12, 2009 FASEB Conference on Proteases in Hemostasis and Vascular Biology, Carefree, AZ, PAR Signaling and Vascular Permeability
July 11-16, 2009 Chair, Novel Mechanisms of Antiplatelet Therapy, XXII Congress of the International Society on Thrombosis and Haemostasis, Boston, MA
May 2-7, 2010 Gordon Research Conference on Proteolytic Enzymes and Their Inhibitors, Platelet Proteases and Protease-Activated Receptor-1, Il Ciocco-Barga, Italy
June 2, 2010 Speaker and Panelist ”Our Journey: Founders talk of their companies”, Massachusetts Life Sciences Innovation Day 2010, Boston, MA
Sept 2-4, 2010 6th International Meeting ADP2010, Villa Cagnola, Grazzada-Schianno, Italy (CME accredited lecture)
Nov 4-5, 2010 Co-Chair and Meeting Organizer, 2nd Pepducin Science Symposium, Cambridge, MA
April 9-14, 2011 Use of Pepducins as Potential Therapeutics, ASPET Symposium, FASEB meeting, Washington, D.C.
Sept 21, 2011 Center for Cancer Systems Biology, Dana Farber Cancer Institute, Harvard University, Anisquam, MA
Nov 18, 2011 Department of Pathology and Laboratory Medicine, Boston University School of Medicine, to be held in Boston, MA
Dec 10-11, 2011 Scientific Committee on Thrombosis and Vascular Biology, Metalloproteases and PAR activation, American Society of Hematology, to be held in San Diego, CA
Feb 1-3, 2012 Plenary Lecture, EPI XII Iberian Peptide Meeting, To be held in Alicante, Spain