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Giovanni Melillo, M.D.
SAIC Frederick
National Cancer Institute-Frederick
Address: Building 432, Rm 218
Frederick, MD 21702-1201
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Novel therapeutic strategies related to Hypoxia inducible factor-1 (HIF-1).
Current interests of the DTP-Tumor Hypoxia Laboratory include the development of pharmacological
and molecular strategies targeting hypoxia-inducible factor-1 (HIF-1) activity. In vitro and in
vivo studies support a role for the HIF-1 in angiogenesis and tumor progression. Therefore, HIF-1
is a novel molecular target for development of cancer therapeutics and anti-angiogenic drugs. To
identify novel HIF-1 inhibitors we are developing a screening system based on a luciferase reporter
assay.
A second interest of the laboratory is to identify and characterize novel hypoxia and
HIF-1-inducible genes and to study the molecular mechanisms by which hypoxia promotes gene
expression in the tumor microenvironment. To fully elucidate the gene expression profile under
hypoxic conditions we are using the microarray technique. We are interested in studying hypoxic
induction of novel genes in normal cells infiltrating the tumor (i.e. human monocytes) as well as
in cancer cell lines.
Interactive possibilities and available reagents include: hypoxia-inducible reporter gene
vectors.
Credentials
Dr. Giovanni Melillo obtained his medical doctor degree from the University
of Naples, Italy in 1981. He had his residency and fellowship in Medical
Oncology at the National Tumor Institute in Naples. In 1991 he was awarded
a CNR-NATO international fellowship and he joined the Laboratory of Molecular
Immunoregulation at the NCI-FCRDC as a visiting scientist. He then joined
the Laboratory of Experimental Immunology at the NCI-FCRDC where he characterized
the role of a hypoxia-responsive element in the promoter of the inducible
nitric oxide synthase gene. In July 1996 he became a Clinical associate
at the Clinical Oncology Program of the NCI in Bethesda where he became
interested in the role of hypoxia-induced angiogenesis in tumor progression.
In July 1999 he became a Senior Investigator with the DTP-Tumor Hypoxia
Laboratory at the NCI-Frederick.
His current interests are to develop novel therapeutic strategies to target
hypoxia inducible factor-1 (HIF-1) activity and to identify and characterize
novel hypoxia and HIF-1-inducible genes.
Recent Publications
1. Melillo G.: Inhibiting HIF-1 for cancer therapy. Molecular Cancer Research 4(9):601-605, 2006
2. Calvani M., Rapisarda A., Uranchimeg B., Shoemaker R.H., and Melillo G.: Hypoxic induction of a HIF-1a-dependent bFGF autocrine loop drives angiogenesis in human endothelial cells. BLOOD 107:2705-2712, 2006
3. Kong D., Park E.J., Stephen A.G., Calvani M., Cardellina J.H., Monks A., Fisher R.J., Shoemaker R.H., and Melillo G.: Echinomycin, a small molecule inhibitor of HIF-1 DNA binding activity. Cancer Res. 65:9047-9055, 2005
4. Ryan QC, Headlee D, Acharya M, Sparreboom A, Trepel JB, Ye J, Figg WD, Hwang K, Chung EJ, Murgo A, Melillo G, Elsayed Y, Monga M, Kalnitskiy M, Zwiebel J, Sausville EA: Phase I and Pharmacokinetic Study of MS-275, a Histone Deacetylase Inhibitor, in Patients With Advanced and Refractory Solid Tumors or Lymphoma. J. Clin. Oncol. 23(17):3912-22, 2005
5. Melillo G: HIF-1: a Target for Cancer, Ischemia and Inflammation. Too good to be true? Cell Cycle 3:154-155, 2004
6. Rapisarda A., Uranchimeg B., Sordet O., Pommier Y., Shoemaker R.H., and Melillo G.: Topoisomerase I mediated inhibition of Hypoxia Inducible Factor-1 (HIF-1): mechanism and therapeutic implications. Cancer Res. 64: 1475-1482, 2004
7. Rapisarda A, Zalek J, Hollingshead M, Braunschweig T, Uranchimeg B, Bonomi CA, Borgel SD, Carter JP, Hewitt SM, Shoemaker RH, and Melillo G.: Schedule-dependent inhibition of hypoxia-inducible factor-1alpha protein accumulation, angiogenesis, and tumor growth by topotecan in U251-HRE glioblastoma xenografts. Cancer Res. 64: 6845-6848, 2004
8. Schioppa T., Uranchimeg B., Saccani A., Biswas S.K., Rapisarda A., Bernasconi S., Saccani S., Nebuloni M., Vago L., Mantovani A., Melillo G., and Sica A.: Regulation of the chemokine receptor CXCR4 by hypoxia. J. Exp. Med. 198: 1391-1402, 2003
9. Rapisarda A., Uranchimeg B., Scudiero D.A., Selby M., Sausville E.A., Shoemaker R.H., and Melillo G.: Identification of Small Molecule Inhibitors of Hypoxia Inducible Factor 1 (HIF-1) Transcriptional Activation Pathway. Cancer Res. 62: 4316-4324, 2002
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