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Scientist Profile

Napoleone Ferrara

Genentech Fellow: Research Oncology
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"I am inspired by the possibility of combining exciting basic science with the development of novel therapies for important diseases with an unmet medical need. The field of angiogenesis is exquisitely suitable for such a combination."
 

I joined Genentech in 1988 after finishing a postdoc at the University of California, San Francisco (UCSF). The reputation for great science, combined with a flexible and entrepreneurial atmosphere, were the major factors in my decision to join Genentech.

I had an opportunity to appreciate all of these aspects very soon. Even though my initial project was the development of models to study the activity of relaxin, a hormone thought to be involved in the functioning of the human reproductive system, I also had the freedom to pursue my favorite project, which involved studying a novel vascular endothelial cell growth factor (VEGF) and the biology of the human VEGF protein. I doubt that this would have been possible at other companies.

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My Focus

The main research theme of my lab is the regulation of angiogenesis (the formation of new blood vessels). We identified the gene for human VEGF in 1989 and then characterized this molecule as a major regulator of angiogenesis in a broad variety of circumstances, including embryonic development, reproductive functions and endochondral bone formation. In addition, we demonstrated that VEGF is a key mediator of tumor angiogenesis. These studies led to the development of a humanized anti-VEGF antibody, Avastin® (bevacizumab, rhuMAb-VEGF), which was originally approved by the FDA in February 2004 for the treatment, in combination with 5-FU-based chemotherapy, of first-line metastatic colorectal cancer.

Avastin was then approved in June 2006 for the treatment, in combination with 5-FU-based chemotherapy, of second-line metastatic colorectal cancer. The pivotal Phase III study on Avastin in metastatic colorectal cancer was the first clinical validation of the long-pursued anti-angiogenic hypothesis: that by interfering with a tumor's blood supply, you may inhibit tumor growth and metastasis and thereby provide health benefits to cancer patients. In October 2006, Avastin was also approved in combination with carboplatin and paclitaxel for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer.

My lab's studies on the role of VEGF in intraocular neovascularization also led to the clinical development of an anti-VEGF antibody fragment, Lucentis® (ranibizumab injection), as a potential therapy for wet age-related macular degeneration. In June 2006, Lucentis was approved for the treatment of neovascular (wet) age-related macular degeneration (AMD). Overall, I am very excited about this anti-VEGF product and its potential role in the treatment of various diseases with high unmet medical needs.

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My Interests

Currently, my lab is investigating mechanisms of tumor angiogenesis alternative to VEGF, as well as studying novel, tissue-selective, endothelial cell mitogens. As part of this latter initiative, my team isolated endocrine gland vascular endothelial growth factor (EG-VEGF), a molecule that forms new blood vessels only in endocrine-system tissues.

This breakthrough finding suggests that there may be ways to turn the blood supply on and off to specific parts of the body - a finding that may have therapeutic implications not only for cancer, but heart disease, wound healing, and blindness. My team's findings about EG-VEGF were published in Nature in August 2001 and have been summarized on PubMed.

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Publications & Recognition
  • Microglial Wnt ligands suppress retinal angiogenesis via activation of the VEGF inhibitor Flt1.
  • Nature. In press.
  • Stefater, JA, Lewkowich, I, Rao, S, Ajima, R, Mariggi, G, Wills-Karp, M, Pollard, J, Yamaguchi, T, McMahon, AP, Ferrara, N, Gerhardt, H, Lang, RA.
  • G-CSF promotes lung metastasis through mobilization of Ly6G+Ly6C+ granulocytes.
  • Proc. Natl. Acad. Sci. USA. 104, 21248-21255, 2010.
  • Kowanetz, M, Wu, X, Qu, X, Tan, M, Hagenbeeck, T, Ross, J, Korsisaari, N, Cao, T, Bou-Reslan, H, Kallop, D, Weimer, R, Ludlam, MC, Kaminker, JS, Modrusan, Z, van Bruggen, N, Peale, FV, Carano, R, Meng, YG, Ferrara, N.
  • View Abstract on PubMed
  • Vascular endothelial growth factor and age-related macular degeneration: from basic science to therapy.
  • Nature Med. 16, 1107-1111, 2010.
  • Ferrara, N.
  • View Abstract on PubMed
 
View All Publications & Recognition
 
  • University of California, San Francisco
  • Cancer Research Institute, Postdoctoral Research Fellow
  • 1986-1988
  • The Oregon Health Sciences University
  • Department of Obstetrics and Gynecology, Intern
  • 1985-1986
  • University of California, San Francisco
  • Reproductive Endocrinology Center, Research Fellow
  • 1983-1985
  • University of Catania Medical School, Catania, Italy
  • Department of Obstetrics and Gynecology, Resident
  • 1981-1985
  • University of Catania Medical School, Catania, Italy
  • M.D.
  • 1974-1981
  • Liceo Classico M. Cutelli, Catania, Italy
  • M. Classica
  • 1969-1974
Publications & Recognition
  • Microglial Wnt ligands suppress retinal angiogenesis via activation of the VEGF inhibitor Flt1.
  • Nature. In press.
  • Stefater, JA, Lewkowich, I, Rao, S, Ajima, R, Mariggi, G, Wills-Karp, M, Pollard, J, Yamaguchi, T, McMahon, AP, Ferrara, N, Gerhardt, H, Lang, RA.
  • G-CSF promotes lung metastasis through mobilization of Ly6G+Ly6C+ granulocytes.
  • Proc. Natl. Acad. Sci. USA. 104, 21248-21255, 2010.
  • Kowanetz, M, Wu, X, Qu, X, Tan, M, Hagenbeeck, T, Ross, J, Korsisaari, N, Cao, T, Bou-Reslan, H, Kallop, D, Weimer, R, Ludlam, MC, Kaminker, JS, Modrusan, Z, van Bruggen, N, Peale, FV, Carano, R, Meng, YG, Ferrara, N.
  • View Abstract on PubMed
  • Vascular endothelial growth factor and age-related macular degeneration: from basic science to therapy.
  • Nature Med. 16, 1107-1111, 2010.
  • Ferrara, N.
  • View Abstract on PubMed
  • Targeting the tumor vasculature: insights from physiological angiogenesis.
  • Nat. Rev. Cancer. 10, 505-514, 2010.
  • Chung, AS, Lee, J, Ferrara, N.
  • View Abstract on PubMed
  • PlGF blockade does not inhibit angiogenesis during primary tumor growth.
  • Cell 2010; 141(1):166-177.
  • Bais C, Wu X, Yao J, Crawford Y, McCutcheon K, Tan C, Yang S, Vernes JM, Easthan-Anderson J, Haughney P, Kowanetz M, Hagenbeck T, Kasman I, Meng G, Hongo JA, Stephan JP, Shibuya M, Ferrara N.
  • Autocrine VEGF signaling synergizes with EGFR in tumor cells to promote epithelial cancer development.
  • Cell 2010 Jan 22; 140(2): 268-79.
  • Lichtenberger BM, Tan PK, Niederleithner H, Ferrara N, Petzelbauer P, Sibilia M.
  • View Abstract on PubMed
  • Tumor and stromal pathways mediating refractoriness/resistance to anti-angiogenic therapies.
  • Trends Pharmacol Sci 2009 Dec; 30(12): 624-30.
  • Crawford Y, Ferrara N.
  • View Abstract on PubMed
  • G-CSF-initiated myeloid cell mobilization and angiogenesis mediate tumor refractoriness to anti-VEGF therapy in mouse models.
  • Proc Natl Acad Sci USA 2009 Apr 21; 106(16): 6742-7.
  • Shojaei F, Wu X, Qu X, Kowanetz M, Yu L, Tan M, Meng YG, Ferrara N.
  • View Abstract on PubMed
  • PDGF-C mediates the angiogenic and tumorigenic properties of fibroblasts associated with tumors refractory to anti-VEGF treatment.
  • Cancer Cell 2009 Jan 6; 15(1): 21-34.
  • Crawford Y, Kasman I, Yu L, Zhong C, Wu X, Modrusan Z, Kaminker J, Ferrara N.
  • View Abstract on PubMed
  • The molecular basis of vascular lumen formation in the developing mouse aorta.
  • Dev Cell 2009 Oct; 17(4): 505-15.
  • Strilic B, Kucera T, Eglinger J, Hughes MR, McNagny KM, Tsukita S, Dejana E, Ferrara N, Lammert E.
  • View Abstract on PubMed
  • Role of Bv8 in neutrophil-dependent angiogenesis in a transgenic model of cancer progression.
  • Proc Natl Acad Sci USA 2008 Feb 19; 105(7):2640-5.
  • Shojaei F, Singh M, Thompson JD, Ferrara N.
  • View Abstract on PubMed
  • Bv8 modulates myeloid cell-dependent tumour angiogenesis.
  • Nature 2007 Dec 6; 450, 825-831, 2007.
  • Shojaei F, Wu X, Zhong C, Yu L, Liang XH, Yao J, Blanchard D, Peale F, Bais C, Van Bruggen N, Ho C, Ross J, Tan M, Carano R, Meng YG, Ferrara N.
  • View Abstract on PubMed
  • Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells.
  • Nat Biotechnol 2007 Aug; 25(8): 911-20. Epub 2007 Jul 29.
  • Shojaei F, Wu X, Baldwin ME, Zhong C, Malik A, Shanz S, Fuh G, Gerber HP , Ferrara N.
  • View Abstract on PubMed
  • Inhibition of VEGF-A prevents the angiogenic switch and results in increased survival of Apc+/min mice.
  • Proc Natl Acad Sci U S A 2007 Jun 19; 104(25): 10625-30. Epub 2007 Jun 6.
  • Korsisaari N, Kasman I, Forrest W, Pal N, Fuh G, Peale F, Smits R, Ferrara N.
  • View Abstract on PubMed
  • Mice expressing a humanized form of VEGF-A may provide insights into the safety and efficacy of anti-VEGF antibodies.
  • Proc Natl Acad Sci U S A 2007 Feb 27; 104(9): 3478-83.
  • Gerber HP, Wu X, Yu L, Wiesmann C, Liang XH, Lee CV, Fuh G, Olsson C, Damico L, Xie D, Meng YG, Gutierrez J, Corpuz R, Li B, Hall L, Rangell L, Ferrando R, Lowman H, Peale F, Ferrara N.
  • View Abstract on PubMed
  • Endothelium- microenvironment interactions in the developing embryo and in the adult.
  • Dev Cell 2007 Feb; 12(2): 181-94.
  • Red-Horse K, Crawford Y, Shojaei F, Ferrara N.
  • View Abstract on PubMed
  • Targeting VEGF-A to treat cancer and age-related macular degeneration.
  • Annu Rev Med 2007; 58: 491-504.
  • Ferrara N, Mass RD, Campa C, Kim R.
  • View Abstract on PubMed
  • Corneal avascularity is due to soluble VEGF receptor-1.
  • Nature 2006 Oct 26; 443(7114): 993-7.
  • Ambati BK, Nozaki M, Singh N, Takeda A, Jani PD, Suthar T, Albuquerque RJ, Richter E, Sakurai E, Newcomb MT, Kleinman ME, Caldwell RB, Lin Q, Ogura Y, Orecchia A, Samuelson DA, Agnew DW, St Leger J, Green WR, Mahasreshti PJ, Curiel DT, Kwan D, Marsh H, Ikeda S, Leiper LJ, Collinson JM, Bogdanovich S, Khurana TS, Shibuya M, Baldwin ME, Ferrara N, Gerber HP, De Falco S, Witta J, Baffi JZ, Raisler BJ, Ambati J.
  • View Abstract on PubMed
  • Development of ranibizumab, an anti-vascular endothelial growth factor antigen binding fragment, as therapy for neovascular age-related macular degeneration.
  • Retina 2006 Oct; 26(8): 859-70.
  • Ferrara N, Damico L, Shams N, Lowman H, Kim R.
  • View Abstract on PubMed
  • Vascular endothelial growth factor signaling pathways: therapeutic perspective.
  • Clin Cancer Res 2006 Sep 1; 12(17): 5018-22.
  • Kowanetz M, Ferrara N.
  • View Abstract on PubMed
  • Tumor-driven paracrine platelet-derived growth factor receptor alpha signaling is a key determinant of stromal cell recruitment in a model of human lung carcinoma.
  • Clin Cancer Res 2006 May 1; 12(9): 2676-88.
  • Tejada ML, Yu L, Dong J, Jung K, Meng G, Peale FV, Frantz GD, Hall L, Liang X, Gerber HP, Ferrara N.
  • View Abstract on PubMed
  • The vascular basement membrane: a niche for insulin gene expression and Beta cell proliferation.
  • Dev Cell 2006 Mar; 10(3): 397-405.
  • Nikolova G, Jabs N, Konstantinova I, Domogatskaya A, Tryggvason K, Sorokin L, Fassler R, Gu G, Gerber HP, Ferrara N, Melton DA, Lammert E.
  • View Abstract on PubMed
  • Angiogenesis as a therapeutic target.
  • Nature 2005 Dec 15; 438(7070): 967-74.
  • Ferrara N, Kerbel RS.
  • View Abstract on PubMed
  • Bv8 and endocrine gland-derived vascular endothelial growth factor stimulate hematopoiesis and hematopoietic cell mobilization.
  • Proc Natl Acad Sci U S A 2004 Nov 30; 101(48): 16813-8.
  • LeCouter J, Zlot C, Tejada M, Peale F, Ferrara N.
  • View Abstract on PubMed
  • VEGF-null cells require PDGFR alpha signaling-mediated stromal fibroblast recruitment for tumorigenesis.
  • EMBO J 2004 Jul 21; 23(14): 2800-10.
  • Dong J, Grunstein J, Tejada M, Peale F, Frantz G, Liang WC, Bai W, Yu L, Kowalski J, Liang X, Fuh G, Gerber HP, Ferrara N.
  • View Abstract on PubMed
  • Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer.
  • Nat Rev Drug Discov 2004 May; 3(5): 391-400.
  • Ferrara N, Hillan KJ, Gerber HP, Novotny W.
  • View Abstract on PubMed
  • Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer.
  • N Engl J Med 2004 Jun 3; 350(23): 2335-42.
  • Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F.
  • View Abstract on PubMed
  • Angiogenesis-independent endothelial protection of liver: role of VEGFR-1.
  • Science 2003 Feb 7; 299(5608): 890-3.
  • LeCouter J, Moritz DR, Li B, Phillips GL, Liang XH, Gerber HP, Hillan KJ, Ferrara N.
  • View Abstract on PubMed
  • VEGF regulates haematopoietic stem cell survival by an internal autocrine loop mechanism.
  • Nature 2002 Jun 27; 417(6892): 954-8.
  • Gerber HP, Malik AK, Solar GP, Sherman D, Liang XH, Meng G, Hong K, Marsters JC, Ferrara N.
  • View Abstract on PubMed
  • VEGF and the quest for tumour angiogenesis factors.
  • Nature Rev. Cancer. 2, 795-803, 2002.
  • Ferrara, N.
  • Identification of an angiogenic mitogen selective for endocrine gland endothelium.
  • Nature 2001 Aug 30; 412(6850): 877-84.
  • LeCouter J, Kowalski J, Foster J, Hass P, Zhang Z, Dillard-Telm L, Frantz G, Rangell L, DeGuzman L, Keller GA, Peale F, Gurney A, Hillan KJ, Ferrara N.
  • View Abstract on PubMed
  • A repressor sequence in the juxtamembrane domain of Flt-1 (VEGFR-1) constitutively inhibits vascular endothelial growth factor-dependent phosphatidylinositol 3'-kinase activation and endothelial cell migration.
  • EMBO J 2000 Aug 1; 19(15): 4064-73.
  • Gille H, Kowalski J, Yu L, Chen H, Pisabarro MT, Davis-Smyth T, Ferrara N.
  • View Abstract on PubMed
  • VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation.
  • Nat Med 1999 Jun; 5(6): 623-8.
  • Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N.
  • View Abstract on PubMed
  • Vascular endothelial growth factor is essential for corpus luteum angiogenesis.
  • Nat Med 1998 Mar; 4(3): 336-40.
  • Ferrara N, Chen H, Davis-Smyth T, Gerber HP, Nguyen TN, Peers D, Chisholm V, Hillan KJ, Schwall RH.
  • View Abstract on PubMed
  • Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders.
  • Cancer Res 1997 Oct 15; 57(20): 4593-9.
  • Presta LG, Chen H, O'Connor SJ, Chisholm V, Meng YG, Krummen L, Winkler M, Ferrara N.
  • View Abstract on PubMed
  • Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene.
  • Nature 1996 Apr 4; 380(6573): 439-42.
  • Ferrara N, Carver-Moore K, Chen H, Dowd M, Lu L, O'Shea KS, Powell-Braxton L, Hillan KJ, Moore MW.
  • View Abstract on PubMed
  • Regulation by vascular endothelial growth factor of human colon cancer tumorigenesis in a mouse model of experimental liver metastasis.
  • J Clin Invest 1995 Apr; 95(4): 1789-97.
  • Warren RS, Yuan H, Matli MR, Gillett NA, Ferrara N.
  • View Abstract on PubMed
  • Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders.
  • N Engl J Med 1994 Dec 1; 331(22): 1480-7.
  • Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE, Nguyen H, Aiello LM, Ferrara N.
  • View Abstract on PubMed
  • Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo.
  • Nature 1993 Apr 29; 362(6423): 841-4.
  • Kim KJ, Li B, Winer J, Armanini M, Gillett N, Phillips HS, Ferrara N.
  • View Abstract on PubMed
  • The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor.
  • Science 1992 Feb 21; 255(5047): 989-91.
  • de Vries C, Escobedo JA, Ueno H, Houck K, Ferrara N, Williams LT.
  • View Abstract on PubMed
  • Vascular endothelial growth factor is a secreted angiogenic mitogen.
  • Science 1989 Dec 8; 246(4935): 1306-9.
  • Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N.
  • View Abstract on PubMed
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Awards & Honors
  • Dr. Paul Janssen Award for Biomedical Research 2011
  • Special Recognition, ARVO/AFER 2011
  • Lasker~DeBakey Clinical Medical Research Award 2010
  • Jules Gonin Lecture, Retina Research Foundation 2010
  • Macula Society, Michaelson Symposium Award 2010
  • Mortel Lecturership in Cancer Research, Penn State University 2009
  • Pezcoller Foundation-AACR International Award 2009
  • NDDO Honorary Award Lecture 2009
  • Macula Society, Arnall Patz Award 2008
  • Bruce I. Terman Memorial Lecture, Albert Einstein College of Medicine 2008
  • Doctor honoris causa, University of Eastern Piedmont, Novara, Italy 2007
  • ASCO Science of Oncology Award 2007
  • C. Chester Stock Award, MSKCC 2007
  • Society for Medicines Research Award 2006
  • General Motors Cancer Research Award 2006
  • Elected to the National Academy of Sciences, USA 2006
  • Passano Award 2006
  • Lefoulon-Delalande-Institut de France 2005
  • AACR Bruce F. Cain Memorial Award 2005
  • Discover Magazine Award for Medicine 2004
  • American-Italian Cancer Foundation Prize 2004
  • AIRCMO Prize for Research in Opthalmic Disorders 2004
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Ellen Filvaroff, Senior Scientist and Alex Avardo, Receipent of Free Medicine From the Genentech® Access to Care Foundation, on the cover of Genentech's 2006 Annual Report.