Oncogenic activation in a mouse model for acute promyelocytic leukemia

Dr. Thomas Sternsdorf, The Salk Institute, La Jolla, California, USA

On Monday June 27th, 2005 at 2.15pm, Dr. Thomas Sternsdorf, a former PhD student and research fellow at the HPI, will be our guest HPI-seminar speaker. His is very well known for his pioneering work on the functions and autoantigenicity of components of PML- and related bodies, multiprotein complexes with a distinct nuclear dot-like distribution and with presumed functions in virtually all known physiological processes of cells.
Among the many seminal discoveries Dr. Sternsdorf made range of the identification and functional analysis of posttranslational modification of some PML-components by ubiquitin-like proteins, the elucidation of some aspects of their role in leukemogenesis in unique murine models, as well as the demonstration of the functional modulation of P53 by recruitment into PML-bodies by a specific PML-isoform and the identification of a transcriptional modulator function of the AIRE protein, which has a dominant autoimmunity inducing function leading to autoimmune polyglandular syndrome 1, a devastating human autoimmune disease.

Dr. Sternsdorf, is currently a senior scientist at THE SALK Institute, La Jolla, California, USA in the department of Prof. Ron Evans. This laboratory is famous for an incredible number of breakthrough discoveries in the life sciences, for which Dr. Evans was honored in 2004 with the Lasker Award, a strong predictor of future Noble prize winners. Understanding of the molecular genetics of metabolic disease (including arteriosclerosis and diabetes) and cancer (including breast cancer, colon cancer, and leukemia) are major research areas of this laboratory. Establishment of so-called marathon mice resistant to weight gain even in the absence of exercise by modulation of nuclear PPARdelta receptor expression is the most spectacular recent published achievement (for more information on R. Evans Lab see www.salk.edu).

Dr. Sternsdorf´s work is focussed on the understanding of basic mechanisms leading to leukemias. The role of receptors in cell differentiation and cell transformation, a major topic in Evan´s Lab, is of major concern in this research. Dr. Sternsdorf is using retro- and lentiviruses for transduction of hematopoetic stem cells with potentially oncogenic proteins as a tool for induction of acute promyelocytic leukemia. He will present exciting new data obtained with a retroviral-mediated forced protein dimerisation/dissociation approach for activation and switch-off of oncogenic processes.