Faculty

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Yves Albert Declerck, MD
Professor of Pediatrics
Pediatrics
CHL Mail Stop 54 Off Campus Los Angeles
+1 323 361 2150

Overview

Yves De Clerck, M.D. is the director of the Saban Research Institute of Childrens Hospital Los Angeles and a professor of pediatrics, biochemistry and molecular biology at the Keck School of Medicine of USC. He is also co-leader of the Tumor Microenvironment Program. Dr. Clerck is currently leading an NIH-funded research study on the mechanisms of tumor invasion and metastasis with a primary focus on neuroblastoma—the second most common solid tumor in children—and melanoma. He has been a researcher studying the role of the tumor microenvironment and cancer progression for more than 25 years. A native of Brussels, Belgium, he earned his bachelor’s degree, magna cum laude, from Notre Dame University in Belgium, and his medical degree, summa cum laude, from the Catholic University of Louvain, Belgium. He is a permanent member of the NIH Study Section of Tumor Progression and Metastasis, and serves on the Tumor Microenvironment Study Section in addition to other advisory boards at the NIH. He is currently on the editorial board of several scientific journals including Cancer Research, Clinical Cancer Research, Cancer Microenvironment, and the Journal of Cell Physiology. He has been an active participant in the American Association for Cancer Research (AACR) Scientist-Survivor Program for many years and has chaired two AACR sponsored conferences. Professional memberships include the AACR where he was the chair of the Local Liaison Committee for the 2005 Annual Meeting, the American Association for the Advancement of Science, and the American Society of Cell Biology. He is funded by three research grants from the NIH and has authored and co-authored more than 100 papers.

Publications

The Tumor Microenvironment at a Turning Point Knowledge Gained Over the Last Decade, and Challenges and Opportunities Ahead: A White Paper from the NCI TME Network. Cancer Res. 2017 Mar 01; 77(5):1051-1059. View in: PubMed

More than the genes, the tumor microenvironment in neuroblastoma. Cancer Lett. 2016 Sep 28; 380(1):304-14. View in: PubMed

Fat, Calories, and Cancer. Cancer Res. 2016 Feb 1; 76(3):509-10. View in: PubMed

Interaction between bone marrow stromal cells and neuroblastoma cells leads to a VEGFA-mediated osteoblastogenesis. Int J Cancer. 2015 Aug 15; 137(4):797-809. View in: PubMed

Plasminogen Activator Inhibitor-1 in Cancer: Rationale and Insight for Future Therapeutic Testing. Cancer Res. 2015 Aug 1; 75(15):2969-74. View in: PubMed

Small Molecule Inhibitors of Plasminogen Activator Inhibitor-1 Elicit Anti-Tumorigenic and Anti-Angiogenic Activity. PLoS One. 2015; 10(7):e0133786. View in: PubMed

MYCN-Dependent Expression of Sulfatase-2 Regulates Neuroblastoma Cell Survival. Cancer Res. 2014 Nov 1; 74(21):5999-6009. View in: PubMed

Bone marrow-derived mesenchymal stromal cells promote survival and drug resistance in tumor cells. Mol Cancer Ther. 2014 Apr; 13(4):962-75. View in: PubMed

[Tumor microenvironment and therapeutic resistance process]. Med Sci (Paris). 2014 Apr; 30(4):445-51. View in: PubMed

Targeting the tumor microenvironment: from understanding pathways to effective clinical trials. Cancer Res. 2013 Aug 15; 73(16):4965-77. View in: PubMed

Critical role of STAT3 in IL-6-mediated drug resistance in human neuroblastoma. Cancer Res. 2013 Jul 1; 73(13):3852-64. View in: PubMed

Protumorigenic activity of plasminogen activator inhibitor-1 through an antiapoptotic function. J Natl Cancer Inst. 2012 Oct 3; 104(19):1470-84. View in: PubMed

Desmoplasia: a response or a niche? Cancer Discov. Desmoplasia: a response or a niche? Cancer Discov. 2012 Sep; 2(9):772-4. View in: PubMed

Tumor microenvironment complexity: emerging roles in cancer therapy. Cancer Res. 2012 May 15; 72(10):2473-80. View in: PubMed

Sorafenib inhibits endogenous and IL-6/S1P induced JAK2-STAT3 signaling in human neuroblastoma, associated with growth suppression and apoptosis. Cancer Biol Ther. 2012 May 1; 13(7):534-41. View in: PubMed

A galectin-3-dependent pathway upregulates interleukin-6 in the microenvironment of human neuroblastoma. Cancer Res. 2012 May 1; 72(9):2228-38. View in: PubMed

Runx2 promotes both osteoblastogenesis and novel osteoclastogenic signals in ST2 mesenchymal progenitor cells. Osteoporos Int. 2012 Apr; 23(4):1399-413. View in: PubMed

Synergistic Activity of Fenretinide and the Bcl-2 Family Protein Inhibitor ABT-737 against Human Neuroblastoma. Clin Cancer Res. 2011 Nov 15; 17(22):7093-104. View in: PubMed

A phase I study of zoledronic acid and low-dose cyclophosphamide in recurrent/refractory neuroblastoma: a new approaches to neuroblastoma therapy (NANT) study. Pediatr Blood Cancer. 2011 Aug; 57(2):275-82. View in: PubMed

Microsomal prostaglandin E synthase-1 enhances bone cancer growth and bone cancer-related pain behaviors in mice. Life Sci. 2011 Apr 11; 88(15-16):693-700. View in: PubMed

Stromelysin-1 (MMP-3) is a target and a regulator of Wnt1-induced epithelial-mesenchymal transition (EMT). Cancer Biol Ther. 2010 Jul; 10(2):198-208. View in: PubMed

Bone marrow-derived mesenchymal stem cells and the tumor microenvironment. Cancer Metastasis Rev. 2010 Jun; 29(2):249-61. View in: PubMed

Interleukin-6 in bone metastasis and cancer progression. Eur J Cancer. 2010 May; 46(7):1223-31. View in: PubMed

Valpha24-invariant NKT cells mediate antitumor activity via killing of tumor-associated macrophages. J Clin Invest. 2009 Jun; 119(6):1524-36. View in: PubMed

Interleukin-6 in the bone marrow microenvironment promotes the growth and survival of neuroblastoma cells. Cancer Res. 2009 Jan 1; 69(1):329-37. View in: PubMed

Bone marrow microenvironment and tumor progression. Cancer Microenviron. 2008 Dec; 1(1):23-35. View in: PubMed

Plasminogen activator inhibitor-1 protects endothelial cells from FasL-mediated apoptosis. Cancer Cell. 2008 Oct 7; 14(4):324-34. View in: PubMed

Identification of galectin-3-binding protein as a factor secreted by tumor cells that stimulates interleukin-6 expression in the bone marrow stroma. J Biol Chem. 2008 Jul 4; 283(27):18573-81. View in: PubMed

The activity of zoledronic Acid on neuroblastoma bone metastasis involves inhibition of osteoclasts and tumor cell survival and proliferation. Cancer Res. 2007 Oct 1; 67(19):9346-55. View in: PubMed

Oncogene MYCN regulates localization of NKT cells to the site of disease in neuroblastoma. J Clin Invest. 2007 Sep; 117(9):2702-12. View in: PubMed

The cyclin-dependent kinase inhibitors p15INK4B and p21CIP1 are critical regulators of fibrillar collagen-induced tumor cell cycle arrest. J Biol Chem. 2007 Aug 17; 282(33):24471-6. View in: PubMed

Tumor progression and metastasis from genetic to microenvironmental determinants: a workshop of the tumor progression and metastasis NIH study section in honor of Dr. Martin L. Padarathsingh, May 31, 2006, Georgetown, Washington, DC. Cancer Biol Ther. 2006 Dec; 5(12):1588-99. View in: PubMed

Mechanisms of invasion and metastasis in human neuroblastoma. Cancer Metastasis Rev. 2006 Dec; 25(4):645-57. View in: PubMed

Multimodal imaging analysis of tumor progression and bone resorption in a murine cancer model. J Comput Assist Tomogr. 2006 May-Jun; 30(3):525-34. View in: PubMed

Matrix metalloproteinases play an active role in Wnt1-induced mammary tumorigenesis. Cancer Res. 2006 Mar 1; 66(5):2691-9. View in: PubMed

Modifying the soil to affect the seed: role of stromal-derived matrix metalloproteinases in cancer progression. Cancer Metastasis Rev. 2006 Mar; 25(1):35-43. View in: PubMed

Mechanisms of pericyte recruitment in tumour angiogenesis: a new role for metalloproteinases. Eur J Cancer. 2006 Feb; 42(3):310-8. View in: PubMed

Discoidin domain receptor 2 mediates tumor cell cycle arrest induced by fibrillar collagen. J Biol Chem. 2005 Dec 2; 280(48):40187-94. View in: PubMed

Mechanisms of bone invasion and metastasis in human neuroblastoma. Cancer Lett. 2005 Oct 18; 228(1-2):203-9. View in: PubMed

Considering the critical interface between tumor cells and stromal cells in the search for targets for anticancer therapy. Cancer Cell. 2005 May; 7(5):408-9. View in: PubMed

The contribution of bone marrow-derived cells to the tumor vasculature in neuroblastoma is matrix metalloproteinase-9 dependent. Cancer Res. 2005 Apr 15; 65(8):3200-8. View in: PubMed

Bone marrow mesenchymal stem cells provide an alternate pathway of osteoclast activation and bone destruction by cancer cells. Cancer Res. 2005 Feb 15; 65(4):1129-35. View in: PubMed

Assessing growth and response to therapy in murine tumor models. Methods Mol Med. 2005; 111:335-50. View in: PubMed

Focus on the cell membrane: the need for dissociation and detachment in tumoral invasion. Cancer Biol Ther. 2004 Jul; 3(7):632-3. View in: PubMed

The matrix metalloproteinase inhibitor prinomastat enhances photodynamic therapy responsiveness in a mouse tumor model. Cancer Res. 2004 Apr 1; 64(7):2328-32. View in: PubMed

Proteases, extracellular matrix, and cancer: a workshop of the path B study section. Am J Pathol. 2004 Apr; 164(4):1131-9. View in: PubMed

Differential inhibition of membrane type 3 (MT3)-matrix metalloproteinase (MMP) and MT1-MMP by tissue inhibitor of metalloproteinase (TIMP)-2 and TIMP-3 rgulates pro-MMP-2 activation. J Biol Chem. 2004 Mar 5; 279(10):8592-601. View in: PubMed

Stromal matrix metalloproteinase-9 regulates the vascular architecture in neuroblastoma by promoting pericyte recruitment. Cancer Res. 2004 Mar 1; 64(5):1675-86. View in: PubMed

TIMP-2 is released as an intact molecule following binding to MT1-MMP on the cell surface. Exp Cell Res. 2004 Feb 1; 293(1):164-74. View in: PubMed

Meeting report: Proteases, extracellular matrix, and cancer: an AACR Special Conference in Cancer Research. Cancer Res. 2003 Aug 1; 63(15):4750-5. View in: PubMed

Lytic bone lesions in human neuroblastoma xenograft involve osteoclast recruitment and are inhibited by bisphosphonate. Cancer Res. 2003 Jun 15; 63(12):3026-31. View in: PubMed

Gene therapy for hepatocellular carcinoma using non-viral vectors composed of bis guanidinium-tren-cholesterol and plasmids encoding the tissue inhibitors of metalloproteinases TIMP-2 and TIMP-3. Cancer Gene Ther. 2003 Jun; 10(6):435-44. View in: PubMed

Computerized quantification of tissue vascularization using high-resolution slide scanning of whole tumor sections. J Histochem Cytochem. 2003 Feb; 51(2):151-8. View in: PubMed

New approaches to the biology of melanoma: a workshop of the National Institutes of Health Pathology B Study Section. Am J Pathol. 2002 Nov; 161(5):1949-57. View in: PubMed

Plasminogen activator inhibitor-1 promotes angiogenesis by stimulating endothelial cell migration toward fibronectin. Cancer Res. 2001 Jul 15; 61(14):5587-94. View in: PubMed

TGF-beta3-induced palatogenesis requires matrix metalloproteinases. Mol Biol Cell. 2001 May; 12(5):1457-66. View in: PubMed

Tissue inhibitor of metalloproteinase (TIMP)-2 acts synergistically with synthetic matrix metalloproteinase (MMP) inhibitors but not with TIMP-4 to enhance the (Membrane type 1)-MMP-dependent activation of pro-MMP-2. J Biol Chem. 2000 Dec 29; 275(52):41415-23. View in: PubMed

Contact with fibrillar collagen inhibits melanoma cell proliferation by up-regulating p27KIP1. Proc Natl Acad Sci U S A. 2000 Aug 29; 97(18):10026-31. View in: PubMed

NF-Y and Sp1 cooperate for the transcriptional activation and cAMP response of human tissue inhibitor of metalloproteinases-2. J Biol Chem. 2000 Jun 16; 275(24):18602-10. View in: PubMed

Interactions between tumour cells and stromal cells and proteolytic modification of the extracellular matrix by metalloproteinases in cancer. Eur J Cancer. 2000 Jun; 36(10):1258-68. View in: PubMed

Magnetic resonance imaging for the evaluation of a novel metastatic orthotopic model of human neuroblastoma in immunodeficient mice. Clin Exp Metastasis. 2000; 18(6):455-61. View in: PubMed

Tissue inhibitors of matrix metalloproteinases in cancer. Ann N Y Acad Sci. 1999 Jun 30; 878:108-19. View in: PubMed

Identification of the TIMP-2 binding site on the gelatinase A hemopexin C-domain by site-directed mutagenesis and the yeast two-hybrid system. Ann N Y Acad Sci. 1999 Jun 30; 878:747-53. View in: PubMed

The plasminogen-plasminogen activator (PA) system in neuroblastoma: role of PA inhibitor-1 in metastasis. Cancer Res. 1999 Mar 15; 59(6):1327-36. View in: PubMed

Identification of the tissue inhibitor of metalloproteinases-2 (TIMP-2) binding site on the hemopexin carboxyl domain of human gelatinase A by site-directed mutagenesis. The hierarchical role in binding TIMP-2 of the unique cationic clusters of hemopexin modules III and IV. J Biol Chem. 1999 Feb 12; 274(7):4421-9. View in: PubMed

Tissue inhibitors of metalloproteinases (TIMP) in invasion and proliferation. APMIS. 1999 Jan; 107(1):111-9. View in: PubMed

Urokinase induces receptor mediated brain tumor cell migration and invasion. J Neurooncol. 1998 Dec; 40(3):215-26. View in: PubMed

Matrix metalloproteinases-2 and -9 are expressed in human neuroblastoma: contribution of stromal cells to their production and correlation with metastasis. Cancer Res. 1998 May 15; 58(10):2209-16. View in: PubMed

Tissue inhibitor of metalloproteinase-2 (TIMP-2) binds to the catalytic domain of the cell surface receptor, membrane type 1-matrix metalloproteinase 1 (MT1-MMP). J Biol Chem. 1998 Jan 9; 273(2):1216-22. View in: PubMed

Establishment of long-term in vitro cultures of human ovarian cystadenomas and LMP tumors and examination of their spectrum of expression of matrix-degrading proteinases. Gynecol Oncol. 1997 Dec; 67(3):277-84. View in: PubMed

Tissue inhibitor of metalloproteinases-2 is expressed in the interstitial matrix in adult mouse organs and during embryonic development. Mol Biol Cell. 1997 Aug; 8(8):1513-27. View in: PubMed

The C-terminal domain of tissue inhibitor of metalloproteinases-2 is required for cell binding but not for antimetalloproteinase activity. Biochem Biophys Res Commun. 1997 Jul 9; 236(1):100-5. View in: PubMed

Proteases and protease inhibitors in tumor progression. Adv Exp Med Biol. 1997; 425:89-97. View in: PubMed

Structure and characterization of the human tissue inhibitor of metalloproteinases-2 gene. J Biol Chem. 1996 Oct 11; 271(41):25498-505. View in: PubMed

Overexpression of tissue inhibitor of metalloproteinases-2 retroviral-mediated gene transfer in vivo inhibits tumor growth and invasion. Cancer Res. 1996 Jul 1; 56(13):2891-5. View in: PubMed

Cloning and partial structure of the gene encoding human tissue inhibitor of metalloproteinases-3. Gene. 1996 May 8; 170(2):287-8. View in: PubMed

Independent regulation of matrix metalloproteinases and plasminogen activators in human fibrosarcoma cells. J Cell Physiol. 1996 May; 167(2):333-40. View in: PubMed

Cooperation between matrix metalloproteinases and the plasminogen activator-plasmin system in tumor progression. Enzyme Protein. 1996; 49(1-3):72-84. View in: PubMed

Effect of tissue inhibitor of the matrix metalloproteinases-2 expression on the growth and spontaneous metastasis of a human melanoma cell line. Cancer Res. 1994 Oct 15; 54(20):5467-73. View in: PubMed

Protease inhibitors: role and potential therapeutic use in human cancer. Eur J Cancer. 1994; 30A(14):2170-80. View in: PubMed

Direct activation of human neutrophil procollagenase by recombinant stromelysin. Biochem J. 1993 Oct 15; 295 ( Pt 2):581-6. View in: PubMed

Characterization of the functional domain of tissue inhibitor of metalloproteinases-2 (TIMP-2). Biochem J. 1993 Jan 1; 289 ( Pt 1):65-9. View in: PubMed

Prolonged clinical response to vincristine treatment in two patients with idiopathic hypereosinophilic syndrome. Am J Pediatr Hematol Oncol. 1992 Nov; 14(4):348-51. View in: PubMed

Inhibition of invasion and metastasis in cells transfected with an inhibitor of metalloproteinases. Cancer Res. 1992 Feb 1; 52(3):701-8. View in: PubMed

Inhibition of tumor invasion of smooth muscle cell layers by recombinant human metalloproteinase inhibitor. Cancer Res. 1991 Apr 15; 51(8):2151-7. View in: PubMed

Inhibition of autoproteolytic activation of interstitial procollagenase by recombinant metalloproteinase inhibitor MI/TIMP-2. J Biol Chem. 1991 Feb 25; 266(6):3893-9. View in: PubMed

Inhibition of collagenolytic activity and metastasis of tumor cells by a recombinant human tissue inhibitor of metalloproteinases. J Natl Cancer Inst. 1990 Apr 4; 82(7):589-95. View in: PubMed

Purification and characterization of a collagenase inhibitor produced by bovine vascular smooth muscle cells. Arch Biochem Biophys. 1988 Aug 15; 265(1):28-37. View in: PubMed

Differential collagen biosynthesis by human neuroblastoma cell variants. Cancer Res. 1987 Dec 15; 47(24 Pt 1):6505-10. View in: PubMed

Cellular interactions in graft-v-host disease. Transplant Proc. 1987 Dec; 19(6 Suppl 7):52-4. View in: PubMed

c-myc amplification and expression in newly established human osteosarcoma cell lines. Cancer Res. 1987 Jul 15; 47(14):3808-14. View in: PubMed

Inhibition of tumor cell collagenolytic activity by bovine endothelial cells. Cancer Res. 1986 Jul; 46(7):3580-6. View in: PubMed

Collagen biosynthesis in human neuroblastoma cell lines: evidence for expression of glial cell properties. J Natl Cancer Inst. 1985 Sep; 75(3):431-9. View in: PubMed

Degradation of the subendothelial matrix by tumor cells. Cancer Res. 1983 Apr; 43(4):1827-34. View in: PubMed

Degradation of artificial tissue substrates. Symp Fundam Cancer Res. 1983; 36:177-85. View in: PubMed

Effect of ascorbic acid on the resistance of the extracellular matrix to hydrolysis by tumor cells. Cancer Res. 1980 Sep; 40(9):3228-31. View in: PubMed

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