April 2008
LICR's First Spin-off Company Acquired by Roche
LICR’s first spin-off company, PIramed Limited, was acquired in April by the pharmaceutical company Roche. Since its foundation in 2003, PIramed has developed small molecule inhibitors targeting PI-3 kinases (PI3Ks), a family of enzymes involved in a signaling pathway that is disrupted in most types of cancer. One of the company’s products, which targets PI3-K-alpha, is currently undergoing clinical development for cancer in collaboration with Genentech. Read more here
New LICR Oxford Branch Laboratories Completed
On April 2nd, Dr. Xin Lu, Director of the LICR Oxford Branch, welcomed members of the LICR New York Office to the Branch’s new facilities in a state-of-the-art building on the Old Road Campus in Oxford. The new Branch is affiliated with the Nuffield Department of Clinical Medicine which is part of the Medical Sciences Division of the University of Oxford. Read more - and see photographs - here
Research Profile: Colin Goding, Ph.D., LICR Oxford Branch
Dr. Colin Goding, formerly head of the Signaling and Development Group at the Marie Curie Research Institute (MCRI) in Oxted, UK, joined the Oxford Branch as a Member on January 8th with six of his current team members (four post-doctoral fellows, a clinical research fellow and a PhD student). Through more than twenty years of research on malignant melanoma—a cancer that is increasingly common and particularly dangerous since it easily metastasizes—Dr. Goding and his colleagues have established effective strategies to investigate how changes in the cell’s gene regulation programs lead to the onset and progression of cancer. Read a summary of Dr. Goding's research here
Research Profile: Gareth Bond, Ph.D., LICR Oxford Branch
Dr. Gareth Bond joined the Oxford Branch as an Assistant Member on January 15 and moved to the UK from the USA, where he formerly held a position at the Institute for Advanced Study (IAS) in Princeton, New Jersey. He is currently recruiting both PhD students and postdoctoral fellows as he builds up a research group to study how variations in the human genetic code contribute to the onset and progression of cancer. Read a summary of Dr. Bond's research here
Symposium for Michael D. Waterfield, F.R.S.
On April 1st, 1986, Dr. Michael Waterfield became the Founding Director of the London University College Branch of LICR. Exactly twenty two years later, approximately 100 of Dr. Waterfield’s former students and colleagues gathered at The Royal Society in London to celebrate his research contributions and acknowledge his mentorship of generations of scientists.Read more - and see the program - here
Recapitulating Year One of the Hilton Ludwig Cancer Metastasis Initiative
A year ago, the Institute formed a partnership with the Conrad N. Hilton Foundation to create the Hilton-Ludwig Cancer Metastasis Initiative (HLCMI), an extensive research effort specifically focused on metastasis. The HLCMI has provided the strategies and resources needed for a diverse group of LICR investigators and collaborators to join forces in attempting to understand metastasis, the direct cause of nearly all cancer deaths. Read a report here
Dr. Ken Pang Receives 2008 Fulbright Postdoctoral Scholarship
Dr. Ken Pang, postdoctoral fellow at the LICR Melbourne Center, has been awarded a prestigious Fulbright Postdoctoral Scholarship to conduct research at Harvard University’s Department of Molecular and Cellular Biology.Read more here
Research Highlights
Reversing Anergy with a Sugar
In tumors, cytolytic T cells (CTLs) appear to be exhausted or anergic, i.e. experiencing a loss in their ability to recognize tumors. A Brussels Branch team has found that T-cell receptors of anergic CTLs fail to co-localize with their CD8 co-receptors, most likely due to their binding to the protein Galectin. The study was featured on the front cover of the March 2008 issue of Immunity. Receptor co-localization and CTL function can be restored in anergic CTLs by administration of the Galectin-binding sugar molecule LacNAc, suggesting that Galectin ligands could be used to augment the efficacy of vaccine-based immunotherapies.
Demotte N, Stroobant V, Courtoy PJ, Van Der Smissen P, Colau D, Luescher IF, Hivroz C, Nicaise J, Squifflet JL, Mourad M, Godelaine D, Boon T, van der Bruggen P. Restoring the association of the T cell receptor with CD8 reverses anergy in human tumor-infiltrating lymphocytes. Immunity. 2008 Mar;28(3):414-24 [PMID: 18342010]
Better Vaccines with Natural Peptides?
Cancer vaccines are often prepared with ‘analog’ peptides, which resemble natural peptides of cancer antigens but have been modified to enhance their immunogenicity. Such vaccines are known to elicit abundant T cell responses, but these responses may in fact not be optimal for fighting tumors. In a clinical study conducted by Lausanne Branch investigators, vaccination of melanoma patients with an analog peptide produced immune responses that were less effective in recognizing and targeting tumors than those obtained with a corresponding natural peptide. The study supports a rationale of developing cancer vaccines that combine natural peptides with powerful immune-stimulating adjuvants.
Speiser DE, Baumgaertner P, Voelter V, Devevre E, Barbey C, Rufer N, Romero P. Unmodified self antigen triggers human CD8 T cells with stronger tumor reactivity than altered antigen. Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3849-54 [PMID: 18319339]
ChIP-SNP
Standard microarray technologies allow scientists to study the regulation of individual genes on a genome-wide scale, but generally fail to detect if a gene is differentially regulated on separate alleles. For this reason, San Diego Branch investigators have developed a method to analyze allele-specific gene regulation across the human genome. The method is named ‘ChIP-SNP’ as it combines chromatin immunoprecipitation (ChIP) and single nucleotide polymorphism (SNP) microarray analysis.
Maynard ND, Chen J, Stuart RK, Fan JB, Ren B. Genome-wide mapping of allele-specific protein-DNA interactions in human cells. Nat Methods. 2008 Mar 16 [PMID: 18345007]
Selected Manuscripts
Blood
From the laboratory of Dr. Werner Held (Lausanne Branch):
Coudert JD, Scarpellino L, Gros F, Vivier E, Held W. Sustained NKG2D engagement induces cross-tolerance of multiple distinct NK cell activation pathways. Blood. 2008 Apr 1;111(7):3571-8 PMID: 18198346.
Cancer Immunology, Immunotherapy
From the laboratory of Drs. Pedro Romero and Daniel Spesier (Lausanne Branch):
Jandus C, Bioley G, Speiser DE, Romero P. Selective accumulation of differentiated FOXP3(+) CD4 (+) T cells in metastatic tumor lesions from melanoma patients compared to peripheral blood. Cancer Immunol Immunother. 2008 Apr 15 PMID: 18414854.
Cancer Research
A multi-group collaboration (Melbourne Center):
Ebert LM, Tan BS, Browning J, Svobodova S, Russell SE, Kirkpatrick N, Gedye C, Moss D, Ng SP, MacGregor D, Davis ID, Cebon J, Chen W. The regulatory T cell-associated transcription factor FoxP3 is expressed by tumor cells. Cancer Res. 2008 Apr 15;68(8):3001-9 PMID: 18413770.
Immunity
From the laboratory of Drs. Pierre van der Bruggen and Thierry Boon (Brussels Branch):
Demotte N, Stroobant V, Courtoy PJ, Van Der Smissen P, Colau D, Luescher IF, Hivroz C, Nicaise J, Squifflet JL, Mourad M, Godelaine D, Boon T, van der Bruggen P. Restoring the association of the T cell receptor with CD8 reverses anergy in human tumor-infiltrating lymphocytes. Immunity. 2008 Mar;28(3):414-24 PMID: 18342010.
International Journal of Cancer
From the laboratory of Dr. Anamaria Camargo (São Paulo Branch):
Parmigiani RB, Bettoni F, Grosso DM, Lopes A, Cunha IW, Soares FA, Carvalho AL, Fonseca F, Camargo AA. Antibodies against the cancer-testis antigen CTSP-1 are frequently found in prostate cancer patients and are an independent prognostic factor for biochemical-recurrence. Int J Cancer. 2008 May 15;122(10):2385-90 PMID: 18214856.
Journal of Biological Chemistry
From the laboratory of Dr. Stefan Constantinescu (Brussels Branch):
Dusa A, Staerk J, Elliott J, Pecquet C, Poirel HA, Johnston JA, Constantinescu SN. Substitution of pseudokinase domain residue V617 by large non-polar amino acids causes activation of JAK2. J Biol Chem. 2008 Mar 6; PMID: 18326042.
Journal of Clinical Investigation
From the laboratory of Dr. Matthias Ernest (Melbourne Branch):
Ernst M, Najdovska M, Grail D, Lundgren-May T, Buchert M, Tye H, Matthews VB, Armes J, Bhathal PS, Hughes NR, Marcusson EG, Karras JG, Na S, Sedgwick JD, Hertzog PJ, Jenkins BJ. STAT3 and STAT1 mediate IL-11-dependent and inflammation-associated gastric tumorigenesis in gp130 receptor mutant mice. . J Clin Invest. 2008 Apr 22 PMID: 18431520.
Journal of Immunology
A multi-group collaboration (Brussels Branch):
Carrasco J, Van Pel A, Neyns B, Lethé B, Brasseur F, Renkvist N, van der Bruggen P, van Baren N, Paulus R, Thielemans K, Boon T, Godelaine D. Vaccination of a Melanoma Patient with Mature Dendritic Cells Pulsed with MAGE-3 Peptides Triggers the Activity of Nonvaccine Anti-Tumor Cells. J Immunol. 2008 Mar 1;180(5):3585-93 PMID: 18292586.
Molecular & Cellular Proteomics
From the laboratory of Dr. Huilin Zhou (San Diego Branch):
Albuquerque CP, Smolka MB, Payne SH, Bafna V, Eng J, Zhou H. A multidimensional chromatography technology for in-depth phosphoproteome analysis. Mol Cell Proteomics. 2008 Apr 11 PMID: 18407956.
Nature Methods
From the laboratory of Dr. Bing Ren (San Diego Branch): /p>
Maynard ND, Chen J, Stuart RK, Fan JB, Ren B. Genome-wide mapping of allele-specific protein-DNA interactions in human cells. Nat Methods. 2008 Apr;5(4):307-9 PMID: 18345007.
Oncogene
From the laboratory of Drs. Stefan Constantinescu and Jean-Christophe Renauld (Brussels Branch):
Knoops L, Hornakova T, Royer Y, Constantinescu SN, Renauld JC. JAK kinases overexpression promotes in vitro cell transformation. Oncogene. 2008 Mar 6;27(11):1511-9 PMID: 17873904.
From the laboratory of Dr. Aristidis Moustakas (Uppsala Branch):
Gal A, Sjöblom T, Fedorova L, Imreh S, Beug H, Moustakas A. Sustained TGF beta exposure suppresses Smad and non-Smad signalling in mammary epithelial cells, leading to EMT and inhibition of growth arrest and apoptosis. Oncogene. 2008 Feb 21;27(9):1218-30 PMID: 17724470.
Proceedings of the National Academy of Sciences USA
From the laboratory of Drs. Pedro Romero and Daniel Speiser (Lausanne Branch):
Speiser DE, Baumgaertner P, Voelter V, Devevre E, Barbey C, Rufer N, Romero P. Unmodified self antigen triggers human CD8 T cells with stronger tumor reactivity than altered antigen. Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3849-54 PMID: 18319339.
In Brief
Dr. Richard Kolodner elected to the American Academy of Arts and Sciences
It is our great pleasure to congratulate Dr. Richard Kolodner (Executive Director for Laboratory and Translational Sciences, and Member, San Diego Branch) on his recent election to the American Academy of Arts and Sciences (AAAS). The AAAS membership is one of many tributes to Dr. Kolodner’s accomplishments in the field of cancer genetics: he is also a member of the National Academy of Sciences, serves on several academic boards, and has received numerous awards and honors. Dr. Kolodner was the first to demonstrate that DNA repair genes have a critical role in suppressing cancer and clarified the molecular basis for hereditary colon cancers. The AAAS was founded around 1780 to promote the advancement of learning in the USA and is today an international society that honors excellence in science, scholarship, business, public affairs, and the arts.
Mr. Edward McDermott Walks the Great Wall of China
On April 19, LICR President Mr. Edward McDermott joined a challenging walk along the Great Wall of China. The walk was organized by the Australian celebrity and breast cancer survivor Ms. Olivia Newton-John to raise funds for building the Olivia Newton-John Cancer Centre (ONJCC) in Melbourne. When completed, the ONJCC will be the new host of the LICR Melbourne Center and of the cancer services of the Austin Hospital. As LICR’s representative, Mr. McDermott joined Ms. Newton-John during a five-day route of the hike, which covered a total distance of 228km along the Great Wall in three weeks. Other participants included Drs. Andrew Scott and Jonathan Cebon from the LICR Melbourne Center, and various celebrities and cancer survivors. The walk was intended to symbolize the steps cancer patients must take on their road to recovery. For more information visit the website www.greatwalktobeijing.com
Mr. McDermott high above the Yellow River.
Dr. Olivier Michielin Receives the 2008 Leenaards Prize
The prize was established in 1999 by the Leenaards Foundation to support biomedical research within institutions based in the Lake Geneva Region and is awarded yearly to two or three groups of young investigators. Dr. Olivier Michielin (Assistant Member, LICR Lausanne Branch) receives this year’s prize for the ongoing development of a new method for imaging of blood vessels involved in tumor growth and metastasis. Three other Lausanne Branch investigators have previously been awarded the Leenaards prize: Drs. Freddy Radtke, in 2001; Frédéric Lévy, in 2004; and Werner Held, in 2006.
Dr. José Baselga Receives the 2008 AACR-Rosenthal Family Foundation Award
LICR Scientific Advisory Committee Member Dr. José Baselga (Director of Medical Oncology, Hematology and Radiation Oncology at Vall d'Hebron University Hospital in Barcelona, Spain) is the 32nd Annual Recipient of the American Association for Cancer Research (AACR) Rosenthal Family Foundation Award. Established in 1977, the award recognizes clinical cancer research that has made, or promises to make, notable contributions to the field. Dr. Baselga receives the award for his achievements in improving clinical cancer care; specifically, his contributions to the clinical development of novel targeted cancer therapies including studies with anti-EGFR agents, anti-HER2 monoclonal antibodies and biomarker-driven early clinical trials. Dr. Baselga presented his award lecture on April 15th at the AACR meeting in San Diego, USA. In 1980, the award was given to Dr. Samuel Hellman (A.N. Pritzker Distinguished Service Professor at the University of Chicago, USA) who also serves on the LICR Scientific Advisory Committee.
Alumnus Dr. Andrew Wilks Awarded the Order of Australia
Congratulations to former LICR Melbourne Branch Group Leader, Dr. Andrew Wilks, who has just been made an Officer of the Order of Australia (AO), the second-highest award in Australia's honors. Dr. Wilks left LICR to found the Australian biotechnology company Cytopia, which is developing therapies based on the JAK kinases discovered at the LICR Melbourne Branch. Dr. Tony Burgess, LICR Melbourne Branch Director, is a Companion of the Order of Australia (AC), which is the highest of Australia's honors.