giuseppe-murdaca
Dario Marchetti, PhD
Professor of Pathology and Immunology
  • Baylor College of Medicine
    Houston, Texas, USA
    Phone: (713) 798-2335
    E-mail: marchett@bcm.edu

     

Education

  • Diploma di Maturita' Scientifica, “G. Marinelli” Scientific Liceum, Udine, Italy, 1975
  • Doctor of Biology, The University of Pavia, Pavia, Italy, 1979
  • Summa Cum Laude Thesis in Molecular Biology. Thesis title: “Enhancement of the Rate of DNA Polymerase-α Activity on Duplex DNA - dependent ATPase of Mammalian Cells“.
  • Advisor:  Professor Arturo Falaschi, Professor and Scientific Director of United Nations UNIDO, Padriciano - Trieste, Italy

Biography

Dario Marchetti, Ph.D., tumor and molecular biologist, is a tenured Professor in the Department of Pathology & Immunology with a joint appointment in the Department of Molecular & Cellular Biology at Baylor College of Medicine, and the director of the Circulating Tumor Cell (CTC) Core facility at Baylor.

Dr. Marchetti is an international recognized authority in the field of CTCs to combat cancer metastasis for improved patient outcome.  With keen insights into the biology of brain metastasis, he pioneered models for discoveries of molecular determinants underlying brain metastasis and biomarker properties of brain-homing CTCs.

As a consummate scientist, Dr. Marchetti’s bibliography include 179 publications of which 79 are in peer-reviewed journals in the fields of neuroscience and oncology.  He has received numerous awards and secured uninterrupted funding for 25 years by receiving grants from federal, state, institutional and private Agencies.   He is a reviewer for the most prominent journals in cancer research and sits on editorial boards of “Cancer Microenvironment, “Tumor Viruses”, “Vascular Cell”, "Clinical & Experimental Pathology", "International Journal of Oncology", “Cancer Letters”, “Journal of Cellular Biochemistry”, “Discovery/Discovery Reports” (a journal from Harvard Medical School) and "Cancer Metastasis Reviews" among others.  Dr. Marchetti is Editor-in-Chief of The Journal of Gene Therapy and acts as Guest Editor of the International Journal of Molecular Sciences (Basel, Switzerland) on brain metastasis.  Further, he served/serves on grant reviewing panels of the National Institutes of Health of USA and Italy, the Department of Defense of the United States, and is frequently invited as grant reviewer and consultant for multiple national and international Agencies and Companies devoted to oncology research.

Dr. Marchetti graduated from the University of Pavia, Italy in 1979.  He worked as postdoctoral fellow at the University of Illinois, Chicago (1980-1982), University of Texas Medical Branch – Galveston (Texas) (1984-1986).  He then became a research scientist at the University of Texas Health Science Center-Houston (1986-1991), Research Associate and later Instructor at UT MD Anderson Cancer Center (1992-1999), Assistant Professor at UT-Houston (1999-2001), and Associate Professor and later Professor (with tenure) at LSU-Baton Rouge, Louisiana (2002-2007) prior to joining the faculty at Baylor College of Medicine.

Research Interest

  • Brain Metastasis
  • Breast Cancer
  • Mechanisms of Cancer Invasion and Metastasis
  • Circulating Tumor Cells
  • Heparanase
  • Notch1
  • Merlin
  • Cancer Stem Cell Markers
  • The Brain-Metastasis Selected Marker CTC Profile
  • CTC subset characterization
  • Malignant Melanoma
  • Uveal Melanoma
  • CTC Biomarker Discovery and Validation

Scientific Activities

Military or Government Service: Italian Military Service Obligations, 1983

Professional appointments
2014-pres. “Jack L. Titus” Endowed professorship Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX
2008-pres. Professor (with tenure), Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX
2008-pres. Professor (with tenure), Department of Molecular & Cellular Biology (joint appointment), Baylor College of Medicine, Houston, TX 
2008-pres. Director, CTC Core facility, Baylor College of Medicine, Houston, TX
2005-2007 Professor (with tenure) and Director Tumor Biology Laboratories, Department of Comparative Biomedical Sciences, SVM, Louisiana State University at Baton Rouge, Baton Rouge, LA
2001-2005 Associate Professor, Director Tumor Biology Laboratories, Department of Comparative Biomedical Sciences, SVM, Louisiana State University at Baton Rouge, Baton Rouge, LA
1999-2001 Assistant Professor, Department of Neurosurgery, The University of Texas-Houston Health Science Center, Houston, TX
1996-1999 Instructor, Department of Tumor Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX
1991-1996 Research Associate, Department of Tumor Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX
1989-1991 Postdoctoral Research Scientist, Department of Neurology, Baylor College of Medicine, Houston, TX
1986-1989 Research Scientist, The University of Texas (M.D. Anderson Cancer Center, The University of Texas Health Science Center), Houston, TX
1984-1986 Postdoctoral Fellow, Department of Human Biological Chemistry and Genetics, The University of Texas Medical Branch, Galveston, TX
1979-1982 Postdoctoral Fellow, The University of Illinois Health Science Center, Chicago, IL
1979-1980 Teacher Inorganic Chemistry and General Biology, “G. Verga” Scientific Liceum, Pavia, Italy
1975-1979 Pre-doctoral Fellow, The University of Pavia, Pavia, Italy.
Honors and Awards
  • Travel Award - UT M.D. Anderson Cancer Center - The International Cancer Meeting, Rio De Janeiro, Brazil, 1998
  • Travel Award - UT M.D. Anderson Cancer Center -  The International Cancer Chemoprevention Meeting, Nice, France, 1998
  • LSU-SVM Pfizer Award for Research Excellence, LSU-Baton Rouge, 2004
  • Phi Kappa Phi Award for Research Excellence, The Honor Society, LSU-Baton Rouge, 2005 LSU-SVM best MS Thesis Award, mentor for Brian Murry, LSU-Baton Rouge, 2006
  • LSU Dissertation Fellowship Award, mentor for Dr. Madhucchanda Roy, LSU-Baton Rouge, 2006 MAGI Association Scientific Award, Trento, Italy, 2009
  • Cover picture and autobiography, The International Journal of Oncology, 2011 Research Award, The Avon Foundation for Women, New York, NY, 2011-2014 The BCM Alkek Award for Experimental Therapeutics, selected, 2014
  • “Jack L. Titus” Endowed professorship Department of Pathology & Immunology, Baylor College of Medicine, 2014 - present.

Publications

Manuscripts in refereed journals

  1. Marchetti, d., blaustein, d.l., and giacomoni, d. Liposome-mediated insertion of intact dna into isolated nuclei-potential for a new in vitro transcription system. Exp. Cell. Res., 149: 177-187, 1983.
  2. Thorpe, l. W., stach, r.w., hashim, g.a., marchetti, d., and perez-polo, j.r. receptors for nerve growth factor on rat spleen mononuclear cells. Journ. Neurosci. Res., 17: 128-134, 1987.
  3. Marchetti, d., and perez-polo, j.r. nerve growth factor receptors in human neuroblastoma cells.  Journ. Neurochem., 49: 475-486, 1987.
  4. Marchetti, d., stach, r.w., saneto, r.p., devellis, j., and perez-polo, j.r. binding constants of soluble nerve growth factor receptors in rat oligodendrocytes and astrocytes in culture. Biochem. Biophys. Res. Comm., 147: 422-427, 1987.
  5. Wright, l.l., marchetti, d., and perez-polo, j.r. effects on gonadal steroids on nerve growth factor receptors in sympathetic and sensory ganglia of neonatal rats. Int. Journ. Dev. Neurosci., 6: 217-222, 1988.
  6. Linthicum, d.s., bolger, m.b., kussie, p.h., albright, a., linton, a., combs, s., and marchetti, d. Analysis of idiotypic and anti-idiotypic antibodies as models of receptor and ligand.  Clin. Chem., 33: 1676-1680, 1988.
  7. Marchetti, d., van, n.t., gametchu, b., thompson, e.b., kobayashi, y., watanabe, f., and barlogie, b. Flow cytometric analysis of glucocorticoid receptor using monoclonal antibody and fluoresceinated ligand probe. Cancer research, 49: 863-969, 1989.
  8. Morgan, g., thorpe, l.w., marchetti, d., and perez-polo, j.r. expression of nerve growth factor receptors by human peripheral blood mononuclear cells. Journ. Neurosci. Res., 23: 41-45, 1989.
  9. Kussie, p.h., marchetti, d., sherman, m., and linthicum, d.s. molecular analysis of monoclonal idiotypes and anti-idiotypes. Methods enzymology, 178: 91-107, 1989.
  10. Mcmanaman, j.l., oppenheim, r.w., prevette, d., and marchetti, d. Rescue of motoneurons from naturally occurring cell death by a purified skeletal muscle polypeptide: in vivo and in vitro effects of the choline acetyltransferase development factor (cdf). Neuron, 4: 891-898, 1990.
  11. Marchetti, d., and mcmanaman, j.l. characterization of nerve growth factor binding to embryonic rat spinal cord neurons. Journ. Neurosci. Res., 27: 211-218, 1990.
  12. Perez-polo, j.r., werrbach-perez, k., marchetti, d., morgan, b., tagliatatela, g., ramacci, m. T., and angelucci, l. Nerve growth factor activity and aging in the central nervous system. Int. Journ. Clin. Pharm. Res., 10: 15-26, 1990.
  13. Werrbach-perez, k., jackson, g., marchetti, d., morgan, b., thorpe l., and perez- polo, j. R. Growth factor-mediated protection in the aging central nervous system. Prog. Brain res., 86: 183-194, 1990.
  14. Marchetti, d., haverkamp, l.j., clark, r.c., and mcmanaman, j.l. ontogeny of high- and low-affinity nerve growth factor receptors in the lumbar spinal cord of the developing chick embryo.  Developmental biology, 148: 306-313, 1991.
  15. Marchetti, d., menter, d.g., jin, l., nakajima, m., and nicolson, g.l. nerve growth factor effects on human melanoma cell invasion. Int. Journ. Cancer, 55: 692-699, 1993.
  16. Herrmann, j.l., menter, d.g., marchetti, d., hamada, j.-i., nakajima m., and nicolson, g. L. Mediation of ngf-stimulated extracellular matrix invasion by the human melanoma low-affinity p75 neurotrophin receptor: melanoma p75 functions independently of trka. Mol. Biol. Cell, 4(11): 1205-1216, 1993.
  17. Nicolson, g.l., nakajima, m., herrmann, j.h., menter, d.g., cavanaugh, p.g., sik park, j., and marchetti, d. Malignant melanoma metastasis to brain: role of degradative enzymes and responses to paracrine growth factors. Journ. Neuro-oncology, 18: 139-149, 1994.
  18. Cohen, i.r., murdoch, a.d., naso, m.f., marchetti d., bernd, d., and iozzo, r. Abnormal expression of perlecan proteoglycan in metastatic melanoma. Cancer research, 54: 5771-5774, 1994.
  19. Marchetti, d., mccutcheon, i., ross, m.i., and nicolson, g.l. inverse expression of neurotrophin receptors and neurotrophins at the invasion front of brain-metastatic human melanoma tissues. Int. Journ. Oncology, 7: 87-94, 1995.
  20. Menter, d.g., herrmann, j.l., marchetti, d., and nicolson, g.l. involvement of neurotrophins and growth factors in brain metastasis formation.  Invasion and metastasis 14: 372-394, 1995.
  21. Marchetti,  d.,  mcquillan,  d.,  spohn  w.c.,  carson,  d.d.,  and  nicolson,  g.l. neurotrophin stimulation of human melanoma cell invasion: selected nt enhancement of heparanase activity and heparanase degradation of specific heparan sulfate subpopulations. Cancer research, 56(2): 2856-2863, 1996.
  22. Marchetti, d., shouchun, l., spohn, w.c., and carson, d.d. inhibition of heparanase activity by heparan sulfate interacting peptide (hip) and reciprocal hip binding blocking to cell-surface heparan sulfate subpopulations due to heparanase action. The journ. Of biol. Chemistry, 272(25): 15891-15897, 1997.
  23. Marchetti, d., and nicolson, g.l. heparanase in tumor metastasis: degradation of specific heparan sulfate subpopulations due to heparanase action. Adv. Enzyme reg., 37: 111-134, 1997.    
  24. Marchetti, d. Specific degradation of subendothelial matrix  proteoglycans  by human brain-metastatic melanoma/brain endothelial cell heparanases. Journ. Cell. Physiology, 173 (3): 334-342, 1997.
  25. Marchetti, d., and nicolson, g.l. heparanase and heparan sulfate proteoglycans processing in tumor metastasis.  Journ. Inv. Dermatology, 2: 99-105, 1997.
  26. Marchetti, d., parikh, n., sudol, m., and gallick, g.e. stimulation of the protein tyrosine kinase c-yes but not c-src by neurotrophins in human brain-metastatic melanoma cells.  Oncogene, 16 (25): 3253-3260, 1998.
  27. Walch, e.t., albino, a.p., and marchetti, d. Over-expression of the low-affinity p75 neurotrophin receptor correlates with augmented invasion and heparanase production in human malignant melanoma cells.  Int. Journ. Cancer, 82: 112-120, 1999.
  28. Walch, e.t., and marchetti, d.  Role of neurotrophins and neurotrophin receptors in the in vitro invasion and heparanase production of human prostatic cancer cells. Clin. & exp. Metastasis, 17(4): 307-314, 1999.
  29. Marchetti, d., li, j., and shen, r-j. Astrocytes contribute to the brain-metastatic specificity of melanoma cells by producing heparanase. Cancer research, 60: 4767-4770, 2000.
  30. Marchetti, d., and nicolson, g.l. human heparanase: a molecular determinant of brain metastasis. Adv. Enzyme reg., 41: 343-360, 2001.
  31. Marchetti, d., reiland, j., erwin, b., and roy, m. Inhibition of heparanase activity and heparanase-induced angiogenesis by suramin analogues. Int. Journ. Cancer, 104(2): 167-174, 2003.
  32. Marchetti, d., murry, b., galjour, j., and greiter-wilke, a. Human melanoma trkc: its association via a purine-analog-sensitive-kinase activity. Journ. Cell. Biochemistry, 88(5): 865-872, 2003.
  33. Marchetti, d., aucoin, r., blust, j., murry, b., and greiter-wilke, a. The p75 neurotrophin receptor acts as a survival receptor in brain-metastatic melanoma. Journ. Cell.  Biochemistry, 91(1): 206-215, 2004.
  34. Reiland, j., sanderson, r.d., waguespack, m., barker, s., long, r., carson, d.d., and marchetti, d. Heparanase degrades syndecan-1 and perlecan heparan sulfate: functional implications for tumor cell invasion. Journ. Of biol. Chemistry, 279(9): 8047- 8055, 2004.
  35. Aucoin, r., reiland, j., roy, m., and marchetti, d.  Dominant-negative creb inhibits heparanase functionality and melanoma cell invasion.  Journ. Cell. Biochem., 93(2): 215-223, 2004.
  36. Roy, m., reiland, j., chouljenko, v., kousoulas, k.g., and marchetti, d.  Antisense mediated suppression of heparanase gene inhibits melanoma cell invasion. Neoplasia, 7(3): 253-262, 2005.
  37. Murry, b.p., greiter-wilke, a., paulsen, d.b., hiatt, k.m., beltrami, c.a., and marchetti, d.         Selective heparanase localization in malignant melanoma cancers. Int. Journ. Oncology, 26: 345-352, 2005.
  38. Denkins, y., kempf, d., ferniz, m., nileshwar, s., and marchetti, d. Role of omega-3 polyunsaturated fatty acids on cox-2 metabolism in brain-metastatic melanoma. Journ. Lipid   res., 46: 1278-1284, 2005.
  39. Sinnappah-kang, n.d., kaiser, a.j., blust, b., and marchetti, d. Heparanase, trkc, and p75ntr: their functional involvement in human medulloblastoma cell invasion. Int. Journ. Oncology,  27: 617-626, 2005.
  40. Murry, b.p., blust, b., singh, a., foster, t., and marchetti, d. Heparanase mechanisms of melanoma metastasis to the brain: development and use of a brain slice model.  Journ. Cell.  Biochem., 97(2): 217-225, 2006.
  41. Moretti, m.*, sinnappah-kang, n.*, toller, m., curcio, f., and marchetti, d. Hpse-1 expression and functionality in differentiating neural cells. Journ. Neurosci. Res., 83: 694- 701, 2006.   *equal contribution.
  42. El-sayed, k., youssef, d.t.a., marchetti, d., and shaala, l.a.  bioactive natural and semisynthetic latrunculins. The journ. Of nat. Products, 69(2): 219-223, 2006.
  43. Swapnali, s.s., youssef, d.t.a., reiland, j., ferniz, m., marchetti, d., and el- sayed, k.a.   biocatalytic and antimetastatic studies of the marine cembranoids sarcophine and 2-epi-16-deoxysarcophine. The journ. Of nat. Products, 69(7): 1010-1013, 2006.
  44. Reiland, j., kempf, d., roy, m., denkins, y., and marchetti, d. Fgf2 binding, signaling, and angiogenesis are modulated by heparanase in metastatic melanoma cells. Neoplasia, 8(7): 596-606, 2006.
  45. Sinnappah-kang, n., mrak, r.e., paulsen, d.d., and marchetti, d. Prognostic implications of heparanase and trkc/p75ntr expression in human medulloblastoma.  Clin.&  exp. Metastasis, 23: 55-63, 2006.
  46. Brown, a.j., alicknavitch, m., d’souza, s. S., daikoku, t., kirn-safran, c., marchetti, d., carson, d.d., and farach-carson, m.c. heparanase expression and activity influences chondrogenic and osteogenic processes during endochondral bone formation. Bone, 43(4): 689-699, 2008.
  47. S’souza d., yang w., marchetti, d., muir c., julian j., farach-carson m., and carson d.d.  hip/rlp29 antagonizes vegf and fgf2 responses.  Journ. Cell. Biochem., 105(5): 1183-1193, 2008.
  48. Roy m. And marchetti, d. Cell surface heparan sulfate released by heparanase promotes melanoma cell migration and angiogenesis. Journ. Cell. Biochem., 106(2): 200- 209, 2009.
  49. Zhang l., sullivan p. S., suyama , j., and marchetti, d.  Egf - induced heparanase nucleolar localization augments dna topoisomerase i activity in brain-metastatic breast cancer. Mol. Cancer res., 8(2): 278-290, 2010.
  50. Ridgway l. D., wetzel m., and marchetti, d.  Modulation of gef-h1 induced signaling by heparanase in brain-metastatic melanoma cells. Journ. Cell. Biochemistry, 111(5):1299-1309, 2010 (selected as feature article).
  51. Ridgway l. D., wetzel m., and marchetti, d. Heparanase modulates hh and wnt3a signaling in human medulloblastoma cells.  Exp. & ther. Medicine, 2: 229-237, 2011.
  52. Zhang l., sullivan p.s., gunaratne p., goodman j.c., and marchetti, d. Microrna-1258 suppresses breast cancer brain metastasis by targeting heparanase. Cancer research – priority report, 71(3): 645-654, 2011 - selected as one of six breaking advances - highlights from recent cancer literature.  Cancer research, 71 (6): 2025, 2011.
  53. Guo l., fan d., zhang f., lee j.-s., price, j., fidler i., marchetti, d., and langley r. Selection of brain metastasis - initiating breast cancer cells according to growth on hard agar. Am. Journ.  Pathology, 178 (5): 2357-2366, 2011.
  54. Ridgway l. D., wetzel m., epstein a., and marchetti, d.  Heparanase - induced gef-h1 signaling regulates the cytoskeletal dynamics of brain metastatic breast cancer cells.  Molecular cancer research, 10 (6):  689-702, 2012.
  55. Zhang l, ridgway l, wetzel m., ngo j., yin w., kumar d., goodman j.c., groves m., and marchetti, d. The identification and characterization of breast cancer ctcs with brain metastatic competence. Science translational medicine, 5 (180): 84-93, 2013. Commentary by michael clarke. Nature biotech., 31(6): 504-5, 2013.
  56. Camacho l, guerrero p., and marchetti, d.  Microrna and protein profiling of brain metastasis competent cell-derived exosomes. Plos one, 16; 8(9): e73790, 2013.
  57. Guerrero p., yin w, camacho l, and marchetti, d. Oncogenic role of merlin/nf2 in glioblastoma. Oncogene, 2014 jul 21. Doi: 10.1038/onc.2014.185, 2014.
  58. Capuana s., hoyos v., chakraborty r., savoldo b., marchetti d., and dotti g.p. heparanase promotes tumor infiltration and antitumor activity of car-redirected t-lymphocytes, nature medicine, in revision, 2014.
  59. Zhang l., ngo j., wetzel ma, and  marchetti, d.  Heparanase mediates a novel mechanism in  lapatinib-resistant brain metastatic breast cancer.  Neoplasia, in press, 2015.

 

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