LICR NewsLink

June 2004

Dr. Michael D. Waterfield To Step Down As Director of London UC Branch, Dr. Xin Lu Named as Branch Director-Designate

For the first time in LICR history, there will be a hand-over of a Branch Directorship. Earlier this month, the Board of Directors decided that Dr. Xin Lu, a Member at the London St Mary's Branch would be offered the position as successor to Dr. Michael D. Waterfield, the current Branch Director. Dr. Waterfield has decided that he will step down as Director later this year to facilitate the transition and concentrate on his research interests. Dr. Waterfield will be the Head of the LICR/UCL Joint Proteomics Laboratory at UCL, and will continue the study of signal transduction through proteomics.

Dr. Waterfield obtained a Doctorate of Philosophy from the University of London, and then took up Fellowships first at the Department of Medicine at Harvard Medical School, then Massachusetts General Hospital, and then, as a Senior Research Fellow, at the California Institute of Technology with Dr. Leroy Hood. During this period, Dr. Waterfield’s research focus was on the creation and application of advanced protein sequence analysis, and in applying the computational resources for search and comparison biochemistry, particularly the purification, sequencing and quantification of proteins; the subject of his first Nature paper (1).

In 1972, Dr. Waterfield returned to the UK and took up the position of Head of the Protein Chemistry Laboratory of the Imperial Cancer Research Fund (ICRF, now Cancer Research UK). It was shortly after this that Dr. Anne Ridley, the Associate Director of the London UC Branch, recalls that she first met Dr. Waterfield. “I vividly remember being this young post-doc, only having been at ICRF for just a few weeks, and having to present my research plan to the group. In those days, my group and Mike’s group had their lab meetings together, and I can remember being SO nervous because I had to present my research in front of the great Mike Waterfield! Of course, he was charming and really helpful and interested. But I can still remember being really nervous just because he was in the audience!”

Dr. Waterfield made several seminal contributions to cancer research during his time at ICRF. Dr. Waterfield and his team were the first to sequence platelet-derived growth factor (PDGF), supplied by Drs. Deuel and Carl-Henrik Heldin (Director of the LICR Uppsala Branch), using new gas phase sequencers. The team then used search programs to find the relationship with the p28sis oncogene from simian virus. This study was the first to clearly identify the function of an oncogene (2). Then using the same principles, but this time employing purification, sequence and computational searches of a database Dr. Waterfield’s laboratory maintained at ICRF, the group was able to show that the epidermal growth factor receptor (EGFR) became an oncogene when truncated (3). This work was part of a collaboration with Dr. Joseph Schlessinger (now an LICR Affiliate at Yale University, New Haven), and EGFR was the first growth factor receptor purified and sequenced. These results were obtained prior to cloning, which the group then did in collaboration with Dr. Axel Ullrich (4). These findings - the first to definitively show, at a molecular level, that growth factor signaling was central to carcinogenesis - formed the basis of a whole new field of scientific research.

Tony Burgess, the Director of the Melbourne Branch, and a long-time colleague of Dr. Waterfield put these findings in this context. “All scientists strive to participate in a discovery that will change the direction of the world. Most of us work for a lifetime admiring the great achievements of a few of our colleagues and occasionally we brush with one great discovery. In the seven months from June 1983 to January 1984, Mike Waterfield led two great teams which changed our understanding of cancer biochemistry and biology. Ever since those heady days of 1983/4, we have been fortunate to share in the fruits of his vision and technical excellence.”

In 1986, Dr. Waterfield was recruited from ICRF to be the Director of the LICR London University College Branch of Cell and Molecular Biology. He was also appointed Professor of Experimental Oncology at the University College and Middlesex Hospital Medical School. After joining LICR, Dr. Waterfield continued to make significant findings in the field of signal transduction. Some examples include: being one of the first to make inhibitory anti-EGFR monoclonal antibodies (5); identifying the complete primary structure of protein kinase C (PKC) (6); characterization of the EGFR gene (4); and characterization of EGFR and ErbB-2 expression in a variety of tumors. Of course, Dr. Waterfield is also very well known for his research particularly into the phosphatidylinositol 3-kinase (PI3K) family of enzymes, with most being discovered and/or characterized in his LICR laboratory. A research program to develop specific PI3K inhibitors as potential cancer therapies began almost nine years ago with Dr. Waterfield, Dr. Peter Parker (one of the founding group leaders at the LICR UCL Branch, and now at CR UK) and the Japanese pharmaceutical company Yamanouchi. Most recently, this research resulted in the formation of PIRAMED, the first LICR spin-off company.

According to Dr. Munro Neville, the Associate Institute Director and Director of the Office of Intellectual Property, “Dr. Waterfield recognized the potential clinical utility of the PI3K inhibitors arising from his Branch’s interaction with Yamanouchi with uncanny foresight. Under his aegis, a small well funded early stage biotechnology company called PIRAMED based in southern England was launched in 2003 to assess the role of these chemical and related inhibitors, not only in cancer but also in various metabolic, cardiovascular and inflammatory disorders. Progress to date has been impressive and bodes well for the future of the company and its clinical goals.”

Along with his LICR research interests, Dr. Waterfield has also been actively involved with the academic life of University College London (UCL) and its associated hospitals. In 1991, Dr. Waterfield was made the Courtauld Professor of Biochemistry and Molecular Biology at UCL, from 1991 to 2002, he was the Head of UCL’s Department of Biochemistry and Molecular Biology, and from 1998 to 2002, he was Head of the Joint Departments of Biochemistry and Molecular Biology of the Royal Free Hospital School of Medicine and UCL. Dr. Waterfield has also received numerous academic awards, including being made a Fellow of the Royal Society, and is currently the second most highly-cited scientist in the UK.

Despite his personal achievements and awards, Dr. Waterfield sums up his influence in this way: “I am proudest of all of the people that I, and we (the Branch), have trained - 180 postdocs and more than 65 grad students at the UCL Branch! And lots of high achieving group leaders!”

References

1. Richards F.F., Barnes W.T., Lovins R.E., Salomone R., and Waterfield M.D. Quantitative approach to the sequential degradation of proteins and peptides. Nature (1969) 221(187):1241-1244.
2. Waterfield M.D., Scrace G.T., Whittle N., Stroobant P., Johnsson A., Wasteson A., Westermark B., Heldin C.H., Huang J.S., and Deuel T.F. Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus. Nature (1983) 304(5921):35-39.
3. Downward J., Yarden Y., Mayes E., Scrace G., Totty N., Stockwell P., Ullrich A., Schlessinger J., and Waterfield M.D. Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature (1984) 307(5951):521-527.
4. Haley J., Whittle N., Bennet P., Kinchington D., Ullrich A., and Waterfield M. The human EGF receptor gene: structure of the 110 kb locus and identification of sequences regulating its transcription. Oncogene Res. (1987) 1(4):375-396.
5. Gullick W.J., Downward J., Foulkes J.G., and Waterfield M.D. Antibodies to the ATP-binding site of the human epidermal growth factor (EGF) receptor as specific inhibitors of EGF-stimulated protein-tyrosine kinase activity. Eur.J.Biochem. (1986) 158(2):245-253.
6. Parker P.J., Coussens L., Totty N., Rhee L., Young S., Chen E., Stabel S., Waterfield M.D., and Ullrich A. The complete primary structure of protein kinase C--the major phorbol ester receptor. Science (1986) 233(4766):853-859.
7. Bergamaschi D., Samuels Y., O'Neil N.J., Trigiante G., Crook T., Hsieh J.K., O'Connor D.J., Zhong S., Campargue I., Tomlinson M.L., Kuwabara P.E., and Lu X. iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human. Nat.Genet. (2003.
8. Samuels-Lev Y., O'Connor D.J., Bergamaschi D., Trigiante G., Hsieh J.K., Zhong S., Campargue I., Naumovski L., Crook T., and Lu X. ASPP proteins specifically stimulate the apoptotic function of p53. Mol.Cell (2001) 8(4):781-794.