RUDOLF JAENISCH
Official Citation

"Rudolf Jaenisch, Member, Whitehead Institute, and professor of Biology, Massachusetts Institute of Technology, has made fundamental contributions to our knowledge of genome function and regulation. A relentless experimentalist, he has broken barriers by revealing the nature of normal and abnormal mammalian development. Using his insights into epigenetic modification, he has provided a scientific basis for better understanding the risks of human cloning."

Scientific Achievements  |  Biographical Statement  |  Press Release

Scientific Achievements

Rudolf Jaenisch, Pioneer in Mouse Models of Human Disease,
Cancer Research and Cloning

RUDOLF JAENISCH is an adventurous spirit, whether he is hiking in the Himalayas, white water rafting, or tackling challenging research questions.

One of his first pioneering scientific efforts was to help establish transgenic science-making mouse models of human disease. Today, mouse models of diseases such as cancer, epilepsy, hypertension, neurodegenerative disorders, and diabetes are providing new insights into the genetic basis of these diseases. Prior to the development of transgenic science and Dr. Jaenisch's efforts, scientists could only work on cells in tissue culture, which left many questions unanswered because disease is a function of a whole organism, not just a cell in culture.

More recently, his efforts have led him to study such varied research areas as cancer, cloning, and the intrinsic battle in the womb between maternal and paternal genes. This seemingly dissimilar list, has one thing in common-methylation. In mammals, methylation of DNA helps regulate gene expression, or the switching on and off of genes. When a gene is methylated, the cell puts a chemical tag on it, so it is turned off and an unnecessary protein product is not produced from the gene.

Pioneer in Transgenic Science
"Transgenic science is an important research tool because it allows us to make mutations in a gene and study how it affects the whole animal. If we know which mutated gene causes a human disease, we can develop mouse models with the same mutation," explains Dr. Jaenisch.

In the 1970's, Dr. Jaenisch demonstrated for the first time that it was possible to introduce foreign DNA into the cells of the early mouse embryo and show that this DNA would be found in all the tissues of the resulting adult mouse.

Subsequently, Dr. Jaenisch injected leukemia virus into early mouse embryos and showed that the DNA sequence of the leukemia virus had integrated into a specific location in the mouse DNA, and that this trait was passed on to offspring according to the rules of Mendel. These first transgenic animals came down with leukemia, showing that the genetically transmitted viral gene caused the disease.

Throughout his career, Dr. Jaenisch has been at the forefront of mouse genetics. He has set a model for creativity and originality in his research. His contributions have been fundamental and an inspiration to all, say his colleagues.

Methylation
Dr. Jaenisch and his colleagues are also exploring the process of methylation to understand how cancers start, what happens in cloning when the nucleus from an adult cell is "reprogrammed" to produce a new animal, and the unusual pattern of inheritance in some genetic diseases that, for example, are associated with such problems as mental retardation.

Cloning
Dr. Jaenisch's studies on methylation have grown to include cloning. He and his colleagues have described a procedure using mouse embryonic stem cells-cells with the capability to grow into any cell in the body-that greatly increases the efficiency of cloning.

His laboratory has shown that most mice derived by nuclear cloning die during embryonic development and that the few that are born may suffer from serious abnormalities. His lab also has gone on to explore the mechanisms underlying poor survival and gross overgrowth in cloned animals. Dr. Jaenisch and his colleagues found that even seemingly normal-looking clones may harbor serious abnormalities affecting gene expression that may not manifest themselves as outward characteristics.

These results are relevant in the issues of human reproductive cloning and research on human embryonic stem cells. In fact, Dr. Jaenisch has helped educate the public and government officials about this controversial research through seminars, talks, and numerous interviews with the media.

Cancer
"As our cloning technology improves, we also will use mouse cloning to explore early stages in the development of cancer," Dr. Jaenisch says. "Researchers have made a lot of progress in identifying oncogenes, cancer promoting genes, and tumor suppressor genes associated with cancer. However, growing evidence suggests that epigenetic changes also play a crucial role in tumor formation."

"Understanding the relationship between methylation and cancer is essential because we know that methylation can be affected by environmental influences, including drugs and diet," Dr. Jaenisch says. "We want to make sure that efforts to change methylation levels to treat one disease problem don't end up causing another."

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Biographical Statement

RUDOLF JAENISCH was born in Wolfelsgrund, Germany in 1942. He received his M.D. from the University of Munich in 1967 and was a Postdoctoral Fellow first at the Max Planck Institute for Biochemistry, Munich, and then at Princeton University. Following a period as a Visiting Fellow at the Institute for Cancer Research in Philadelphia, Dr. Jaenisch joined the Salk Institute in La Jolla, California, where he remained from 1972 to 1977, rising from Assistant to Associate Research Professor. In 1977 he returned to Germany, where until 1984 he was Head of the Department of Tumor Virology at the Heinrich Pette Institute for Experimental Virology and Immunology at the University of Hamburg. In 1984 Dr. Jaenisch accepted his current position as a Founding Member of the Whitehead Institute for Biomedical Research and Professor of Biology at the Massachusetts Institute of Technology.

Dr. Jaenisch is a pioneer in transgenic science (making mouse models of human disease). These methods have been used to explore basic questions such as the role of DNA modification, genomic imprinting, and X chromosome inactivation. Dr. Jaenisch’s mouse models have produced important advances in understanding cancer, neurological disorders, connective tissue diseases, and developmental abnormalities in muscle and bone. One of the most intriguing models, involving an enzyme called DNA methyltransferase (Mtase), has led to a potential new strategy for cancer therapy. Other models could speed the development of new drugs to fight Alzheimer’s disease or amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease).

Dr. Jaenisch is an elected Fellow of the American Academy of Arts and Sciences and the American Academy of Microbiology, and a Member of the American Academy for the Advancement of Science. In 1996 he was honored with the Boehringer Mannheim Molecular Bioanalytics Prize.

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