Prize for Scientific Excellence in Medicine
The American-Italian Cancer Foundation's Prize for Scientific Excellence in Medicine recognizes important discoveries in cancer biology, prevention, diagnosis and/or treatment. The award is presented annually at the Benefit Dinner & Live Auction in November.
Prize for Scientific Excellence in Medicine Recipients - 2011
Joseph Schlessinger
William H. Prusoff Professor and Chair of Pharmacology
Yale School of Medicine
Joseph Schlessinger, PhD is being nominated to receive the 2011 Prize for Scientific Excellence in Medicine for the identification of the basic mechanisms of receptor tyrosine kinases activation and of signal transduction from the cell surface to the nucleus. These findings have led to the creation of new drugs for cancer and other diseases.
The work carried out by Dr. Schlessinger and his lab has through the years contributed tremendously to our understanding of signal transduction, the process through which cells interpret exogenous signals to respond with proliferation, differentiation or death. In his pioneering studies on the EGF receptor and other tyrosine kinase cell surface receptors, Schlessinger first proposed and demonstrated that receptor activation is initiated by the induction or stabilization of a dimeric state, leading to cross/auto phosphorylation of tyrosine residues within the intracellular portion of the receptor. He showed that protein:protein interactions are also necessary for the assembly and function of signaling molecules and identified protein domains such as PH and SH2 domains that are utilized to recognize specific sequences in the interacting molecules.
Dr. Schlessinger’s lab was also one of the first to obtain and study the crystal structure of tyrosine kinase receptors and to describe the structure of an FGF ligand bound to its receptors. His outstanding productivity in the field of signal transduction has led to numerous other discoveries and provided the conceptual basis for the kinase inhibitors as anticancer drugs, including Sutent, a drug developed by Schlessinger’s group at SUGEN. This drug, now marketed by Pfizer, blocks the receptor kinase activity of the VEGF and PDGF receptors and it is in use for the treatment of renal cell carcinomas and gastric tumors.
David M. Livingston
Emil Frei Professor of Genetics and Medicine, Harvard Medical School
Deputy Director, Dana-Farber/Harvard Cancer Center
David M. Livingston, MD, is being nominated to receive the 2011 Prize for Scientific Excellence in Medicine for his seminal contributions to human cancer science and, specifically, the discovery of key molecular events that control cancer progression, including the RB, p300 and BRCA1 pathways.
During the late 1980s and the mid-1990s, Dr. Livingston and his group made seminal observations that led to the identification of the Rb pathway that controls cell cycle and represents a central process in the maintenance of cellular growth control and cancer suppression. Specifically, his group demonstrated that Tb is cyclically phosphorylated and dephosphorylated during the cell cycle by selected cdk family members and that under phosphorylated Rb exerts a G1 exit blocking effect by binding to its ‘pocket’ domain and suppressing the transactivation function of E2F1. This results in failure to activate key cell cycle progression genes and thereby blockade of exit from G1. Currently, multiple companies are attempting to develop as cancer drugs highly selective cdk inhibitors that activate the Rb pathway.
Dr. Livingston’s laboratory and one other (Dr. Goodman’s) first cloned and discovered the transcriptional coactivation function of p300 and CBP. These proteins were the first, proven transcriptional coactivators, and Livingston showed that they are essential contributors to numerous key biological processes, including organ development, cellular differentiation, cell proliferation, and p53 transcription activation and tumor suppression. His discoveries opened the gene expressional control of a number of these vital processes to ever more penetrating analysis.
Since the mid-1990s, Dr. Livingston’s work has focused on the molecular underpinnings of breast and ovarian cancer development through a multi-pronged attack on the functions of BRCA1 and 2. His group bucked a strong tide in 1997 when they were the first to show that BRCA1 is a genome integrity maintenance protein and not a secreted hormone-like protein as many then believed. Indeed, Livingston’s elegant experiments opened the BRCA1 field to sound functional investigation. His earliest findings also implied—and he and another group (Dr. Jasin’s) later showed directly—that BRCA1 operates in a pathway (the so-called BRCA pathway) dedicated to homologous recombination (HR) repair of double strand DNA breaks, which led over time to the recent discovery by others that Parp1 inhibitors elicit major therapeutic effects in drug-resistant BRCA1 and 2 tumors.
Dr. Livingston is also responsible for multiple discoveries that illuminate key aspects of BRCA1 and 2 function, some of which have denoted the existence of certain BRCA1 partner proteins that, like BRCA1 itself, are HR- maintenance elements and previously undetected breast cancer susceptibility genes. These findings strongly suggest that the maintenance of HR function is a key step in breast cancer suppression. Livingston was also the first to show that BRCA1 is a mitosis-regulating protein as well as a suppressor of small molecule mutagenesis, functions that are also likely contributors to BRCA breast cancer suppression. His collective contributions opened the BRCA field and represent a substantial fraction of its foundation.
Past Recipients
Robert C. Gallo, MD (1984)
Vincent T. DeVita, Jr., MD (1985)
Rita Levi-Montalcini, MD (1987)
Umberto Veronesi, MD (1988)
Gianni Bonadonna, MD and Larry Norton, MD (1990)
Luisa M. Massimo, MD and Philip A. Pizzo, MD (1991)
Harold P. Freeman, MD and Lance A. Liotta, MD, PhD (1992)
Kathleen M. Foley, MD and Vittorio Ventafridda, MD (1993)
Charles M. Balch, MD, FACS and Natale Cascinelli, MD (1994)
Virgil Craig Jordan, OBE, PhD, DSc and Rosella Silvestrini, PhD (1995)
Patrick C. Walsh, MD and Francesco Pagano, MD (1996)
Carlo M. Croce, MD and Bert Vogelstein, MD (1997)
Pier Giuseppe Pelicci, MD, PhD and Rainer F. Storb, MD (1998)
Paul A. Marks, MD and Frances M. Visco, JD (1999)
Alberto Costa, MD and Paul Peter Rosen, MD (2000)
Bernard Levin, MD and Maurizio Ponz de Leon, MD (2001)
Paul A. Bunn, Jr., MD and Gabriella Sozzi, PhD (2002)
Steve Rosenberg, MD, PhD and Andrea Velardi, MD (2003)
Napoleone Ferrara, MD, PhD and Judah Folkman, MD (2004)
Riccardo Dalla-Favera, MD and Pier Paolo Pandolfi, MD, PhD (2005)
Alessandro Massimo Gianni, MD and Irving Weissman, MD, FACS (2006)
José Baselga, MD and John Mendelsohn, MD (2007)
Ronald Levy, MD and Lee M. Nadler, MD (2008)
Brian J. Druker, MD and George D. Demetri, MD (2009)
Mina J. Bissell, PhD and Joseph F. Fraumeni, Jr., MD (2010)
