Micky Tortorella is a former Senior Principal Investigator at Pfizer (2001-2009) with 15 years experience in the pharmaceutical industry. Prior to working at Pfizer he had a successful tenure as a Research Scientist at DuPont Pharmaceuticals (1993-2000). His previous work has focused on understanding the biochemical mechanisms involved in the turnover and degradation of the cartilage matrix, which led to the discovery of ADAMTS-4 and -5, enzymes responsible for aggrecan catabolism in arthritic diseases. His current research continues to focus on elucidating the mechanisms that mediate cartilage and bone degradation during the progression of arthritis and developing therapies for blocking these processes using innovative biochemical, biophysical, molecular and cell imaging technologies. Principal Investigator Tortorella is regarded as a key opinion leader in the United States as well as internationally in osteoarthritis, metalloproteinase biology and in developing pharmaceutical drugs, with over 45 publications in top tier journals and 10 US patents. He has led and provided direction to multiple discovery teams applying basic biology to the drug discovery process, including identification of novel targets, innovation in assay development and the advancement of small molecule inhibitors. Micky Tortorella recently joined GIBH in May 2009 and is responsible for creating and leading an integrated drug discovery centre focused on developing disease modifying pharmaceutical drugs in the areas of oncology, CNS, infectious diseases and arthritis.

1. Talley, J.J., Dan, W.X., Liu, J., Tortorella, M.D., Tu, Z., Zhang,Y. 

Palladium-Catalyzed Synthesis of Trimethylsilyl Substituted BenzopyranDerivatives 

(2013) The Open Organic Chemistry Journal, 7, pp. 15-20.

2. Miller, R.E., Lu, Y., Tortorella, M.D., Malfait, A.-M.

Genetically Engineered Mouse Models Reveal the Importance of Proteases as Osteoarthritis Drug Targets

(2013) Current Rheumatology Reports, 15 (9), pp. 1-15.

3. Morgen, M., Tung, D., Boras, B., Miller, W., Malfait, A.-M., Tortorella, M.

Nanoparticles for improved local retention after intra-articular injection into the knee joint

(2013) Pharmaceutical Research, 30 (1), pp. 257-268. Cited 4 times.

4. Malfait, A.-M., Seymour, A.B., Gao, F., Tortorella, M.D., Le Graverand-Gastineau, M.-P.H., Wood, L.S., Doherty, M., Doherty, S., Zhang, W., Arden, N.K., Vaughn, F.L., Leaverton, P.E., Spector, T.D., Hart, D.J., Maciewicz, R.A., Muir, K.R., Das, R., Sorge, R.E., Sotocinal, S.G., Schorscher-Petcu, A., Valdes, A.M., Mogil, J.S.

A role for PACE4 in osteoarthritis pain: Evidence from human genetic association and null mutant phenotype

(2012) Annals of the Rheumatic Diseases, 71 (6), pp. 1042-1048. Cited 13 times.

5. Zhang, S., Chen, S., Li, W., Guo, X., Zhao, P., Xu, J., Chen, Y., Pan, Q., Liu, X., Zychlinski, D., Lu, H., Tortorella, M.D., Schambach, A., Wang, Y., Pei, D., Esteban, M.A.

Rescue of ATP7B function in hepatocyte-like cells from Wilson's disease induced pluripotent stem cells using gene therapy or the chaperone drug curcumin

(2011) Human Molecular Genetics, 20 (16), art. no. ddr223, pp. 3176-3187. Cited 25 times.

6. Li, J., Anemaet, W., Diaz, M.A., Buchanan, S., Tortorella, M., Malfait, A.M., Mikecz, K., Sandy, J.D., Plaas, A.

Knockout of ADAMTS5 does not eliminate cartilage aggrecanase activity but abrogates joint fibrosis and promotes cartilage aggrecan deposition in murine osteoarthritis models

(2011) Journal of Orthopaedic Research, 29 (4), pp. 516-522. Cited 17 times.

7. Shieh, H.-S., Tomasselli, A.G., Mathis, K.J., Schnute, M.E., Woodard, S.S., Caspers, N., Williams, J.M., Kiefer, J.R., Munie, G., Wittwer, A., Malfait, A.-M., Tortorella, M.D.

Structure analysis reveals the flexibility of the ADAMTS-5 active site

(2011) Protein Science, 20 (4), pp. 735-744. Cited 6 times.

8. Dufield, D.R., Nemirovskiy, O.V., Jennings, M.G., Tortorella, M.D., Malfait, A.M., Mathews, W.R.

An immunoaffinity liquid chromatography-tandem mass spectrometry assay for detection of endogenous aggrecan fragments in biological fluids: Use as a biomarker for aggrecanase activity and cartilage degradation

(2010) Analytical Biochemistry, 406 (2), pp. 113-123. Cited 13 times.

9. Byun, S., Tortorella, M.D., Malfait, A.-M., Fok, K., Frank, E.H., Grodzinsky, A.J.

Transport and equilibrium uptake of a peptide inhibitor of PACE4 into articular cartilage is dominated by electrostatic interactions

(2010) Archives of Biochemistry and Biophysics, 499 (1-2), pp. 32-39. Cited 8 times.

10. Malfait, A.M., Ritchie, J., Gil, A.S., Austin, J.-S., Hartke, J., Qin, W., Tortorella, M.D., Mogil, J.S.

ADAMTS-5 deficient mice do not develop mechanical allodynia associated with osteoarthritis following medial meniscal destabilization

(2010) Osteoarthritis and Cartilage, 18 (4), pp. 572-580. Cited 23 times.

11. Zack, M.D., Melton, M.A., Stock, J.L., Storer, C.E., Barve, R.A., Minnerly, J.C., Weiss, D.J., Stejskal, J.A., Tortorella, M.D., Turk, J.R., Shevlin, K.M., Malfait, A.-M.

Reduced incidence and severity of experimental autoimmune arthritis in mice expressing catalytically inactive A disintegrin and metalloproteinase 8 (ADAM8)

(2009) Clinical and Experimental Immunology, 158 (2), pp. 246-256. Cited 8 times.

12. Tortorella, M.D., Tomasselli, A.G., Mathis, K.J., Schnute, M.E., Woodard, S.S., Munie, G., Williams, J.M., Caspers, N., Wittwer, A.J., Malfait, A.-M., Shieh, H.-S.

Structural and inhibition analysis reveals the mechanism of selectivity of a series of aggrecanase inhibitors

(2009) Journal of Biological Chemistry, 284 (36), pp. 24185-24191. Cited 24 times.

13. Zack, M.D., Malfait, A.-M., Skepner, A.P., Yates, M.P., Griggs, D.W., Hall, T., Hills, R.L., Alston, J.T., Nemirovskiy, O.V., Radabaugh, M.R., Leone, J.W., Arner, E.C., Tortorella, M.D.

ADAM-8 isolated from human osteoarthritic chondrocytes cleaves fibronectin at Ala271

(2009) Arthritis and Rheumatism, 60 (9), pp. 2704-2713. Cited 11 times.

14. Tortorella, M.D., Malfait, F., Barve, R.A., Shieh, H.-S., Malfait, A.-M.

A review of the ADAMTS family, pharmaceutical targets of the future

(2009) Current Pharmaceutical Design, 15 (20), pp. 2359-2374. Cited 25 times.

15. Malfait, A.M., Tortorella, M., Thompson, J., Hills, R., Meyer, D.M., Jaffee, B.D., Chinn, K., Ghoreishi-Haack, N., Markosyan, S., Arner, E.C.

Intra-articular injection of tumor necrosis factor-α in the rat: an acute and reversible in vivo model of cartilage proteoglycan degradation

(2009) Osteoarthritis and Cartilage, 17 (5), pp. 627-635. Cited 6 times.

16. Malfait, A.-M., Arner, E.C., Song, R.-H., Alston, J.T., Markosyan, S., Staten, N., Yang, Z., Griggs, D.W., Tortorella, M.D.

Proprotein convertase activation of aggrecanases in cartilage in situ

(2008) Archives of Biochemistry and Biophysics, 478 (1), pp. 43-51. Cited 38 times.

17. Tortorella, M.D., Malfait, A.M.

Will the real aggrecanase(s) step up: Evaluating the criteria that define aggrecanase activity in osteoarthritis

(2008) Current Pharmaceutical Biotechnology, 9 (1), pp. 16-23. Cited 19 times.

18. Shieh, H.-S., Mathis, K.J., Williams, J.M., Hills, R.L., Wiese, J.F., Benson, T.E., Kiefer, J.R., Marino, M.H., Carroll, J.N., Leone, J.W., Malfait, A.-M., Arner, E.C., Tortorella, M.D., Tomasselli, A.

High resolution crystal structure of the catalytic domain of ADAMTS-5 (aggrecanase-2)

(2008) Journal of Biological Chemistry, 283 (3), pp. 1501-1507. Cited 37 times.

19. Blair, W.S., Cao, J., Jackson, L., Jimenez, J., Peng, Q., Wu, H., Isaacson, J., Butler, S.L., Chu, A., Graham, J., Malfait, A.-M., Tortorella, M., Patick, A.K.

Identification and characterization of UK-201844, a novel inhibitor that interferes with human immunodeficiency virus type 1 gp160 processing

(2007) Antimicrobial Agents and Chemotherapy, 51 (10), pp. 3554-3561. Cited 10 times.

20. Wittwer, A.J., Hills, R.L., Keith, R.H., Munie, G.E., Arner, E.C., Anglin, C.P., Malfait, A.-M., Tortorella, M.D.

Substrate-dependent inhibition kinetics of an active site-directed inhibitor of ADAMTS-4 (aggrecanase 1)

(2007) Biochemistry, 46 (21), pp. 6393-6401. Cited 20 times.

21. Hall, T., Fok, K.F., Liu, M.M., Zobel, J.F., Marino, M.H., Malfait, A.-M., Tortorella, M.D., Tomasselli, A.G.

A high performance liquid chromatography assay for monitoring proprotein convertase activity

(2007) Journal of Chromatography A, 1148 (1), pp. 46-54. Cited 3 times.

22. Hills, R., Mazzarella, R., Fok, K., Liu, M., Nemirovskiy, O., Leone, J., Zack, M.D., Arner, E.C., Viswanathan, M., Abujoub, A., Muruganandam, A., Sexton, D.J., Bassill, G.J., Sato, A.K., Malfait, A.-M., Tortorella, M.D.

Identification of an ADAMTS-4 cleavage motif using phage display leads to the development of fluorogenic peptide substrates and reveals matrilin-3 as a novel substrate

(2007) Journal of Biological Chemistry, 282 (15), pp. 11101-11109. Cited 23 times.

23. Song, R.-H., Tortorella, M.D., Malfait, A.-M., Alston, J.T., Yang, Z., Arner, E.C., Griggs, D.W.

Aggrecan degradation in human articular cartilage explants is mediated by both ADAMTS-4 and ADAMTS-5

(2007) Arthritis and Rheumatism, 56 (2), pp. 575-585. Cited 130 times.

24. Zack, M.D., Arner, E.C., Anglin, C.P., Alston, J.T., Malfait, A.-M., Tortorella, M.D.

Identification of fibronectin neoepitopes present in human osteoarthritic cartilage

(2006) Arthritis and Rheumatism, 54 (9), pp. 2912-2922. Cited 16 times.

25. Tortorella, M.D., Arner, E.C., Hills, R., Gormley, J., Fok, K., Pegg, L., Munie, G., Malfait, A.-M.

ADAMTS-4 (aggrecanase-1): N-Terminal activation mechanisms

(2005) Archives of Biochemistry and Biophysics, 444 (1), pp. 34-44. Cited 48 times.

26. Tortorella, M.D., Arner, E.C., Hills, R., Easton, A., Korte-Sarfaty, J., Fok, K., Wittwer, A.J., Liu, R.-Q., Malfait, A.-M.

α2-Macroglobulin Is a Novel Substrate for ADAMTS-4 and ADAMTS-5 and Represents an Endogenous Inhibitor of These Enzymes

(2004) Journal of Biological Chemistry, 279 (17), pp. 17554-17561. Cited 61 times.

27. Wang, P., Tortorella, M., England, K., Malfait, A.-M., Thomas, G., Arner, E.C., Pei, D.

Proprotein Convertase Furin Interacts with and Cleaves Pro-ADAMTS4 (Aggrecanase-1) in the trans-Golgi Network

(2004) Journal of Biological Chemistry, 279 (15), pp. 15434-15440. Cited 71 times.

28. Tortorella, M.D., Malfait, A.-M.

The Usual Suspects: Verdict Not Guilty?

(2003) Arthritis and Rheumatism, 48 (12), pp. 3304-3307. Cited 10 times.

29. Pratta, M.A., Yao, W., Decicco, C., Tortorella, M.D., Liu, R.-Q., Copeland, R.A., Magolda, R., Newton, R.C., Trzaskos, J.M., Arner, E.C.

Aggrecan Protects Cartilage Collagen from Proteolytic Cleavage

(2003) Journal of Biological Chemistry, 278 (46), pp. 45539-45545. Cited 112 times.

30. Cherney, R.J., Mo, R., Meyer, D.T., Wang, L., Yao, W., Wasserman, Z.R., Liu, R.-Q., Covington, M.B., Tortorella, M.D., Arner, E.C., Qian, M., Christ, D.D., Trzaskos, J.M., Newton, R.C., Magolda, R.L., Decicco, C.P.

Potent and selective aggrecanase inhibitors containing cyclic P1 substituents

(2003) Bioorganic and Medicinal Chemistry Letters, 13 (7), pp. 1297-1300. Cited 31 times.

31. Tortorella, M.D., Liu, R.-Q., Burn, T., Newton, R.C., Arner, E.

Characterization of human aggrecanase 2 (ADAM-TS5): Substrate specificity studies and comparison with aggrecanase 1 (ADAM-TS4)

(2002) Matrix Biology, 21 (6), pp. 499-511. Cited 93 times.

32. Malfait, A.-M., Liu, R.-Q., Ijiri, K., Komiya, S., Tortorella, M.D.

Inhibition of ADAM-TS4 and ADAM-TS5 prevents aggrecan degradation in osteoarthritic cartilage

(2002) Journal of Biological Chemistry, 277 (25), pp. 22201-22208. Cited 170 times.

33. Osman, M., Tortorella, M., Londei, M., Quaratino, S.

Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases define the migratory characteristics of human monocyte-derived dendritic cells

(2002) Immunology, 105 (1), pp. 73-82. Cited 47 times.

34. Tortorella, M.D., Malfait, A.-M., Deccico, C., Arner, E., Nagase, H.

Erratum: The role of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) in a model of cartilage degradation (Osteoarthristis and Cartilage (2001) vol. 9 (6) (539-552))

(2002) Osteoarthritis and Cartilage, 10 (1), p. 82.

35. Yamanishi, Y., Boyle, D.L., Clark, M., Maki, R.A., Tortorella, M.D., Arner, E.C., Firestein, G.S.

Expression and regulation of aggrecanase in arthritis: The role of TGF-β

(2002) Journal of Immunology, 168 (3), pp. 1405-1412. Cited 105 times.

36. Yao, W., Wasserman, Z.R., Chao, M., Reddy, G., Shi, E., Liu, R.-Q., Covington, M.B., Arner, E.C., Pratta, M.A., Tortorella, M., Magolda, R.L., Newton, R., Qian, M., Ribadeneira, M.D., Christ, D., Wexler, R.R., Decicco, C.P.

Design and synthesis of a series of (2R)-N4-hydroxy-2-(3-hydroxybenzyl)-N1- [(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide derivatives as potent, selective, and orally bioavailable aggrecanase inhibitors

(2001) Journal of Medicinal Chemistry, 44 (21), pp. 3347-3350. Cited 49 times.

37. Tortorella, M.D., Malfait, A.-M., Deccico, C., Arner, E.

The role of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) in a model of cartilage degradation

(2001) Osteoarthritis and Cartilage, 9 (6), pp. 539-552. Cited 174 times.

38. Kashiwagi, M., Tortorella, M., Nagase, H., Brew, K.

TIMP-3 Is a Potent Inhibitor of Aggrecanase 1 (ADAM-TS4) and Aggrecanase 2 (ADAM-TS5)

(2001) Journal of Biological Chemistry, 276 (16), pp. 12501-12504. Cited 302 times.

39. Pratta, M.A., Tortorella, M.D., Arner, E.C.

Age-related changes in aggrecan glycosylation affect cleavage by aggrecanase

(2000) Journal of Biological Chemistry, 275 (50), pp. 39096-39102. Cited 57 times.

40. Tortorella, M., Pratta, M., Liu, R.-Q., Abbaszade, I., Ross, H., Burn, T., Arner, E.

The thrombospondin motif of Aggrecanase-1 (ADAMTS-4) is critical for aggrecan substrate recognition and cleavage

(2000) Journal of Biological Chemistry, 275 (33), pp. 25791-25797. Cited 133 times.

41. Tortorella, M.D., Pratta, M., Liu, R.-Q., Austin, J., Ross, O.H., Abbaszade, I., Burn, T., Arner, E.

Sites of aggrecan cleavage by recombinant human aggrecanase-1 (ADAMTS-4)

(2000) Journal of Biological Chemistry, 275 (24), pp. 18566-18573. Cited 162 times.

42. Abbaszade, I., Liu, R.-Q., Yang, F., Rosenfeld, S.A., Ross, O.H., Link, J.R., Ellis, D.M., Tortorella, M.D., Pratta, M.A., Hollist, J.M., Wynn, R., Duke, J.L., George, H.J., Hillman Jr., M.C., Murphy, K., Wiswall, B.H., Copeland, R.A., Decicco, C.P., Bruckner, R., Nagase, H., Itoh, Y., Newton, R.C., Magolda, R.L., Trzaskos, J.M., Hollis, G.F., Arner, E.C., Burn, T.C.

Cloning and characterization of ADAMTS11, an aggrecanase from the ADAMTS family

(1999) Journal of Biological Chemistry, 274 (33), pp. 23443-23450. Cited 346 times.

43. Arner, E.C., Pratta, M.A., Decicco, C.P., Xue, C.-B., Newton, R.C., Trzaskos, J.M., Magolda, R.L., Tortorella, M.D.

Aggrecanase. A target for the design of inhibitors of cartilage degradation

(1999) Annals of the New York Academy of Sciences, 878, pp. 92-107. Cited 42 times.

44. Tortorella, M.D., Burn, T.C., Pratta, M.A., Abbaszade, I., Hollis, J.M., Liu, R., Rosenfeld, S.A., Copeland, R.A., Decicco, C.P., Wynn, R., Rockwell, A., Yang, F., Duke, J.L., Solomon, K., George, H., Bruckner, R., Nagase, H., Itoh, Y., Ellis, D.M., Ross, H., Wiswall, B.H., Murphy, K., Hillman Jr., M.C., Hollis, G.F., Newton, R.C., Magolda, R.L., Trzaskos, J.M., Arner, E.C.

Purification and cloning of aggrecanase-1: A member of the ADAMTS family of proteins

(1999) Science, 284 (5420), pp. 1664-1666. Cited 490 times.

45. Arner, E.C., Pratta, M.A., Trzaskos, J.M., Decicco, C.P., Tortorella, M.D.

Generation and characterization of aggrecanase. A soluble, cartilage- derived aggrecan-degrading activity

(1999) Journal of Biological Chemistry, 274 (10), pp. 6594-6601. Cited 109 times.

46. Arner, E.C., Hughes, C.E., Decicco, C.P., Caterson, B., Tortorella, M.D.

Cytokine-induced cartilage proteoglycan degradation is mediated by aggrecanase

(1998) Osteoarthritis and Cartilage, 6 (3), pp. 214-228. Cited 111 times.

47. Tortorella, M.D., Pratta, M.A., Fox, J.W., Arner, E.C.

The interglobular domain of cartilage aggrecan is cleaved by hemorrhagic metalloproteinase HT-d (Atrolysin C) at the matrix metalloproteinase and aggrecanase sites

(1998) Journal of Biological Chemistry, 273 (10), pp. 5846-5850. Cited 27 times.

48. Trzaskos, J.M., Scherele, P.A., Manos, E.J., Feezer, W.S., Tortorella, M.D., Arner, E.C., Favata, M.F.

Inhibition of mapkk (MEK) prevents upregulation of metalloproteinases in fibroblasts

(1997) FASEB Journal, 11 (9), .

49. Tortorella, M.D., Arner, E.C.

A fluorescent enzyme-linked immunosorbent assay (FELISA) for stromelysin using a polyclonal antisera to human stromelysin with broad species cross-reactivity

(1997) Inflammation Research, 46 (SUPPL. 2), pp. S120-S121. Cited 4 times.

50. Tortorella, M.D., Arner, E.C.

A high-throughput assay for stromelysin using a casein-resorufin substrate

(1997) Inflammation Research, 46 (SUPPL. 2), pp. S122-S123. Cited 7 times.

51. Arner, E.C., Decicco, C.P., Cherney, R., Tortorella, M.D.

Cleavage of native cartilage aggrecan by neutrophil collagenase (MMP-8) is distinct from endogenous cleavage by aggrecanase

(1997) Journal of Biological Chemistry, 272 (14), pp. 9294-9299. Cited 37 times.

52. Arner, E.C., DiMeo, T.M., Pratta, M.A., Tortorella, M.D.

Interleukin-1 induces aggrecanase-mediated cleavage in human articular cartilage without up-regulating stromelysin or glycosaminoglycan release

(1995) Acta Orthopaedica Scandinavica, Supplement, 66 (266), pp. 153-154. Cited 1 time.

53. Arner, E.C., Tortorella, M.D.

Signal transduction through chondrocyte integrin receptors induces matrix metalloproteinase synthesis and synergizes with interleukin-1

(1995) Arthritis and Rheumatism, 38 (9), pp. 1304-1314. Cited 86 times."