Bruno Amati, Ph.D.
Dept. of Experimental Oncology
European Institute of Oncology (IEO)
Via Ripamonti, 435
20141 Milan Italy

Email: bruno.amati@ieo-research.it

Research Description:
Research in our group aims at understanding the biological and molecular pathways by which Myc regulates cell proliferation and oncogenesis. In particular, we are interested in the links between Myc and cell cycle control, focusing on the function of cyclin-dependent kinases (CDKs), their regulatory subunits (cyclins) and their inhibitors (CKIs). We are also exploring the molecular mechanisms by which Myc regulates gene expression, with special emphasis on the co-factors that are recruited by Myc to target promoters in live cells. We are addressing how Myc and these co-factors modify chromatin, and how these modifications participate in transcriptional control. Finally, we are identifying the genes that are directly bound by Myc in the genome of human cells.
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Michael Cole Ph.D.
Professor, Department of Molecular Biology
Lewis Thomas Laboratory
Washington Rd.
Princeton University
Princeton, NJ 08544-1014

Phone: 609-258-5936
Fax: 609-258-4575
Email: mcole@molbio.princeton.edu

Research interests:
We are interested in understanding the basic mechanisms of oncogenic transformation, in particular the function of the Myc and E2F transcription factor families which are misregulated or overexpressed in a large fraction of human cancers. The oncogenic activity of these transcription factors depends on protein domains associated with transcriptional activation, which provides an avenue to study both cancer biology and the mechanisms of gene regulation. Our recent experimental approach has been based on the observation that dominant interfering alleles of the Myc protein form protein complexes with nuclear factors that are essential for Myc and E2F function. The novel factors uncovered in these studies have proven to be components of highly conserved chromatin modifying complexes that function in many other gene regulatory pathways. Studies of these complexes and their role in oncogenic transformation are a primary focus of my current research. We are also interested in defining the functional components of the Myc oncogenic pathway.
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Robert N. Eisenman, Ph.D.
Member, Fred Hutchinson Cancer Research Center
Seattle, WA
Member, National Academy of Sciences

Email: eisenman@fhcrc.org


Research Description:
Our lab studies the "Max Network"- this includes Myc, Max and other Max interacting proteins including Mad, Mnt and Mga. We are interested in the mechanisms underlying transcriptional activation and repression by these proteins and the nature of the specific genes whose expression they regulate. We also employ genetic strategies in mice and flies to understand the biological functions of Max network proteins. more...
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Dean W. Felsher, M.D., Ph.D.
Stanford University School of Medicine
Palo Alto, CA

Email: dfelsher@stanford.edu


Research Description:
My laboratory studies how oncogenes, such as MYC, initiate and susatain tumorigenesis.  We have developed novel model systems whereby we can conditionally activate oncogenes in normal human and mouse cells in tissue culture on in transgenic mice to address three questions:  How does oncogene activation initiate the process of tumorigenesis?  How does oncogene inactivation induce tumor regression?  How do tumors escape the requirement of partiuular oncogenes to sustain their neoplastic properties? 
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Dr. Heiko Hermeking
Molecular Oncology Group
Max-Planck-Institute of Biochemistry
Am Klopferspitz 18 A
D-82152 Martinsried/Munich
Germany

Phone: ++49-(0)-89-8578-2875
Fax: ++49-(0)-89-8578-2540
Email: herme@biochem.mpg.de

http://www.biochem.mpg.de/hermeking/

Research Description:
We are interested in all aspects of c-MYC biology, its role in cancer and its use as a therapeutic target. In order to identify new c-MYC target-genes we have employed SAGE (serial analysis of gene expression) and microarray analysis. Recently, we described the SAGE-based identification of more than 400 genes, which are differentially regulated after ectopic c-MYC expression in primary human cells (Menssen and Hermeking, 2002). After verification using microarray analysis and real-time PCR, some of the c-MYC-induced genes were further characterized using chromatin immuno-precipitation assays to detect the presence of c-MYC at the promoters of these genes (e.g. Cdk4, Cyclin B1, Prohibitin). We are currently analysing some of these genes to determine their relevance for c-MYC-induced phenotypes, as shown in case of the gene encoding cyclin-dependent kinase 4 (Cdk4) (Hermeking et al., 2000).
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Javier León
Molecular Biology of Cancer Group
Dpto. de Biología Molecular, Facultad de Medicina
39011 Santander, Spain

Email: leonj@unican.es


Research Description:
Research in our lab aims to the study of the roles of c-Myc and Mads proteins in leukemia cell growth, apoptosis and differentiation, focusing in myeloid leukemia as our predominant model system. In particular we are interested in:
a) The functional cross-talk between Myc and p53 in the apoptosis and transactivation activities, and the mechanisms underlying the Myc-mediated interference of p53 functions in this model; b) The interference between Myc and the cyclin-dependent kinases inhibitors p21 and p27 at the transcriptional and post-translational levels and its effects on myeloid cell differentiation elicited by these inhibitors; c) The cross-talk between Myc and Ras in the proliferation of chronic myeloid leukemia cells and the activation of downstream targets of Ras pathways; and d) Myc and Mad expression in human chronic myeloid leukemia and the effects on the action of drugs used in this disease.
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Linda Penn, Ph.D.
Senior Scientist
Division of Cellular and Molecular Biology
Ontario Cancer Institute, PMH
Room 9-628
610 University Ave., Toronto, ON
Canada M5G 2M9

Email: lpenn@uhnres.utoronto.ca

Regulation and Function of the Myc Oncogene:
We have focussed on identifying Myc-repressed genes as recent evidence suggests Myc repression is tightly linked to transformation. We have shown that Myc can negatively regulate specific target. To identify additional Myc-induced and repressed gene targets we are conducting a gene CHIP approach. To identify the key function and the critical regions of the Myc protein which are critical for Myc transformation activity we are conducting a detailed structure/function study of the Myc protein. This work is coupled with our recent endeavors to identify Myc-binding proteins critical for Myc function using a novel two-hybrid approach, called the repressed transactivator assay.

Finally, for a myc-activated cell to develop into a tumour, Myc-triggered apoptosis must be controlled and we are delineating the mechanism of Myc-induced death. In addition, to identify genetic events which can inhibit Myc-induced apoptosis and thereby cooperate with Myc in the transformation process, we are using a retroviral cDNA expression system to functionally clone cDNAs whose product can abrogate apoptosis in a manner similar to bcl-2. By this approach we have been able to identify novel genes as well as known genes whose function in apoptosis regulation had not yet been realized. Thus we have a focused research program directed at understanding Myc regulation and function in tumour initiation and progression.
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