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Developmental Therapeutics Program (DTP)
Last Updated: 04/02/15

Annamaria Rapisarda, Ph.D. [Contractor]

SAIC-Frederick Inc.
Frederick National Laboratory for Cancer Research
Building 432, Room 223
Frederick, Maryland 21702-1201
Phone: (301)-846-6685
Fax: (301)-846-6081
Email: rapisardaa@mail.nih.gov

Credentials

Dr. Annamaria Rapisarda obtained her Ph. D in Molecular Biological Science and her Specialization degree in Clinical Pathology from University of Genoa, Italy. She spent four years as a post-doctoral fellow and seven years as a scientist in the Tumor Hypoxia Laboratory, at the National Cancer Institute, under the supervision of Dr. Giovanni Melillo. During this period, she identified a number of HIF-1 (Hypoxia Inducible Factor 1) inhibitors using a cell-based luciferase reporter high throughput screen, including topoisomerase I inhibitors (i.e. topotecan). She characterized the mechanism of action of topoisomerase I inhibitors on the HIF-1 pathway and she validated topotecan as an HIF-1 inhibitor in preclinical models as single agent or in combination with anti-angiogenic therapies. Her studies led to the design of a phase I clinical trial aimed at testing the effects of HIF-1 inhibition in cancer patients using oral topotecan and to another trial combining the topoisomerase I inhibitor EZN2208 with bevacizumab to target HIF-1 dependent responses.

In October 2011, Dr Rapisarda became laboratory head of the TML at the Frederick National Laboratory for Cancer Research. Her research interests are discovery of targets and the development of therapeutic strategies exploiting the tumor microenvironment and physiological abnormalities of tumors resulting from environmental factors or mutations in metabolic enzymes and the translation of laboratory finding to early clinical trials.

Recent Publications

  1. Rapisarda A., Onnis B., Fer N.D., Perez V, Melillo G. Autocrine production of Inteleukin-11 mediates tumorigenicity in hypoxic human cancer cells. The Journal of Clinical Investigation (2012 submitted).
  2. Rapisarda A., Melillo G. Overcoming disappointing results with antiangiogenic therapy by targeting hypoxia. Nat Rev Clin Oncol. 2012 Apr 24;9(7):378-90.
  3. Rapisarda A., Melillo G. Role of the VEGF/VEGFR axis in cancer biology and therapy. Adv Cancer Res. 2012;114:237-67. Review.
  4. Kummar S, Raffeld M, Juwara L, Horneffer Y, Strassberger A, Allen D, Steinberg SM, Rapisarda A, Spencer SD, Figg WD, Chen X, Turkbey IB, Choyke P, Murgo AJ, Doroshow JH, Melillo G. Multihistology, target-driven pilot trial of oral topotecan as an inhibitor of hypoxia-inducible factor-1α in advanced solid tumors. Clin Cancer Res. 2011 Aug 1;17(15):5123-31
  5. Rapisarda, A., Melillo, G. Combination Strategies Targeting Hypoxia Inducible Factor 1 (HIF-1) for Cancer Therapy. In: The tumor microenvironment, Series: Cancer Drug Discovery and Development. Bagley, R.G. (Ed.), Springer Science+Business Media, 2010.
  6. Terzuoli,E., Puppo,M., Rapisarda,A., Uranchimeg,B., Cao,L., Burger,A.M., Ziche,M. and Melillo,G. Aminoflavone, a ligand of the aryl hydrocarbon receptor, inhibits HIF-1alpha expression in an AhR-independent fashion, Cancer Res., 70: 6837-6848, 2010.
  7. Rapisarda,A., Shoemaker,R.H. and Melillo,G. Antiangiogenic agents and HIF-1 inhibitors meet at the crossroads, Cell Cycle, 8: 4040-4043, 2009.
  8. Onnis,B., Rapisarda,A. and Melillo,G. Development of HIF-1 inhibitors for cancer therapy, J.Cell Mol.Med., 13: 2780-2786, 2009.
  9. Rapisarda,A., Hollingshead,M., Uranchimeg,B., Bonomi,C.A., Borgel,S.D., Carter,J.P., Gehrs,B., Raffeld,M., Kinders,R.J., Parchment,R., Anver,M.R., Shoemaker,R.H. and Melillo,G. Increased antitumor activity of bevacizumab in combination with hypoxia inducible factor-1 inhibition, Mol.Cancer Ther., 8: 1867-1877, 2009.
  10. Rapisarda,A. and Melillo,G. Role of the hypoxic tumor microenvironment in the resistance to anti-angiogenic therapies, Drug Resist.Updat., 12: 74-80, 2009.

About the Branch Chief

Dr. Mary K. Wolpert, Ph.D. Dr. Beverly A. Teicher PhD is Chief of the Molecular Pharmaco-logy Branch at NCI, a position that she assumed in early 2011. One focus of the Molecular Pharmacology Branch is target and drug discovery for rare and recalcitrant cancers such as sarcoma and small cell lung cancer. Dr. Teicher completed a PhD in Bioorganic Chemistry at the Johns Hopkins University and postdoctoral training at Yale University School of Medicine. More…