About Leena
Synapsis of the research career of Dr. Peltonen
The major breakthroughs and
successes in molecular medicine are based on the immense developments in
technology and on the innovative use of human study samples and
populations. Throughout of her research career, Dr. Peltonen has recognized
and successfully used the unique properties of the population isolate of
Finland as a living laboratory, and in so doing, has often been the first to
elucidate the genetic basis of an amazing number of human diseases,
initially monogenic and during most recent years also common, polygenic
traits. The results of her research have provided new information of
essential molecular mechanisms in many human diseases and revealed novel
metabolic pathways. Importantly, her research has also had immediate impact
on the diagnostics and carrier screening of numerous disease genes (www.findis.org).
Since early 1980ies, when Dr. Peltonen mapped the locus of Marfan syndrome,
which facilitated the ultimate cloning of the fibrillin gene (the Marfan
disease gene), her group has mapped over 20 monogenic disease genes in
Finnish study samples and positionally cloned 16 of them including the genes
behind two forms of neuronal ceroid lipofuscinosis (NCL), early dementia,
(PLO-SL), an autoimmune disease, APECED, congenital nephrosis, and numerous
early lethal syndromes like Meckel syndrome. The highly successful work of
Dr. Peltonen’s group has been crucial in the launching of the concept of the
use of population isolates in the search of disease genes and today provides
a model example of such research. An important feature of her groups’ work
has constantly been that the research does not stop at establishment of
linkage or identification of mutations, but continues towards detailed
understanding of molecular mechanisms leading to cellular and tissue
consequences in patients. The research generated by her group thus is not
only published in the most respected journals of genetics, but also in the
prestigious journals such as Nature, The EMBO Journal, Journal of
Biological Chemistry, and Nature Structural Biology, evidencing
the high scientific quality of the “post-mutation” functional studies by her
group.
Dr. Peltonen also has also pioneered in the use of population isolates in the genetic analyses of common multifactorial diseases. In 1989 her group established linkage for an osteoarthritis disease gene and this research spawned a number of subsequent studies in other laboratories. Since 1996 her group has published linkage of predisposing loci in five complex disease, including multiple sclerosis, familial combined hyperlipidemia (FCHL), schizophrenia, bipolar disease, small joint osteoarthritis, hypertension, obesity and coronary heart disease. Many of these loci for complex, polygenic diseases were detected in genome wide scans of unique study samples collected from Finnish populations after careful genealogical analyses to provide for maximal use of the “founder mutation” and enrichment of these selected disease genes. Interestingly, many of the “Finnish loci” also have been replicated in samples from more heterogeneous populations and requiring much larger study samples, illustrating the power of special populations in the search of genes predisposing to common health problems. In 2004 the Peltonen group reported the successful isolation of the first gene behind FCHL, encoding a transcription factor USF1, identified by LD mapping and haplotype sharing in Finnish families and the finding was rapidly replicating in several populations. The relationship of USF1 and dyslipidemias is among the best replicated findings in complex disease genetics and quite recently her group established the impact of this gene as a risk factor for cardiovascular disease at the population level. A similar story of the global significance of the Finnish mutation is the DNA-variant behind lactose intolerance, identified by her group in Finnish families in 2002. This particular variant in the enhancer element of the lactase gene has turned out to be the major global variant behind this common trait. A simple DNA test can now be provided worldwide for lactose intolerance thanks to the invention by her group. Most recently her group has identified genes behind multiple sclerosis (PRKCA, the first non-HLA gene in MS) and schizophrenia (DISC1) and again proven their significance in multiple global populations. Her efforts have proven that studies of special populations do not expose peculiar population-specific genes but rather provide cost-efficient shortcuts to the identification of genetic variants of global significance.
One interesting aspect of Dr. Peltonen’s work has been characterization of the cross talk between nuclear and mitochondrial genome. She is one of the few geneticists analyzing the cross talk between nuclear and mitochondrial genome. Her group has mapped three loci predisposing to autosomal deletions and quite recently successfully identified one of these genes (adenine nucleotide translocator). Identification of these genes will have tremendous impact for our understanding of numerous metabolic diseases, which include mitochondrial deletions in the tissue phenotype. One of the highlights of this research was her group paper in Science in 2000 describing the ANT gene as an essential component in the mtDNA maintenance.Publications
Dr.
Peltonen has published 520 original publications and 77 reviews in
peer-reviewed journals. During the last 20 years her papers have appeared
in the leading journals of molecular genetics and molecular biology
including Nature, Science Nature Genetics, Nature Structural Biology, New
England Journal of Medicine, Journal of Clinical Investigations, American
Journal of Human genetics, Human Molecular Genetics, EMBO Journal and
Proceedings of the National Academy of Sciences (USA). These papers
contain a vast quantity of highly original and significant data that has
enormously increased our knowledge of the molecular genetics and molecular
pathogenesis of human diseases, providing some seminal contributions in
molecular medicine. These studies have gained a wide national and
international recognition as reflected by the numerous prizes and honors she
has received. She was honored by the Honorary Doctorship of the University
of Uppsala in January 2000 in the Millennium Promotion celebrating the 400th
anniversary of the Promotion tradition in Scandinavia. In 2003 she obtained
the Margaret Pittman lectureship award, given to eminent female scientists
by NIH and in 2006 she received two international Prizes, the Nordic
Fernström Prize and the European van Gysel Prize. She was also recently
elected into the Institute of Medicine of the National Academy of USA.
Esteemed Scholar
During her 20 years as a senior scientist, Dr. Peltonen has been tremendously productive scientifically. She has launched many new concepts in the field of molecular medicine and beautifully demonstrated the impact of special populations in genetic research. Importantly, her group has provided a unique educational environment for the advanced training of numerous young scientists in the field of molecular medicine. A total of 71 Ph.D. theses have been produced in U.S. and in Finland and many of them have been accepted with honors. Furthermore, out of the 64 Ph.D. students from her group, a total of 45 were M.D/Ph.D. students, underlining the significance of her mentorship in training of future clinicians with professional expertise in molecular medicine. Dr. Peltonen also has organized numerous international scientific symposia and courses, thus establishing her role, internationally, as a science educator.
Dr. Peltonen was the founder and
the Gordon and Virginia MacDonald Distinguished Chair of the Department of
Human Genetics at UCLA. During her years at UCLA in 1998-2002, Dr. Peltonen
appointed 19 faculty members to constitute the new department, including 8
faculty members who have achieved both the M.D. and Ph.D. degree. In 2003
when back in her native Finland, she obtained an Academy Professorship, the
highest recognition of the excellence in research in Finland. She has been
the Director of the Center of Excellence in Disease Genetics of the Academy
of Finland (www.ktl.fi/diseasegenetics)
and the Nordic Center of Excellence in Disease Genetics (www.ncoedg.org), as
well as the Co-ordinator of one of the three Genomics Centers funded by EU (www.genomeutwin,org).
In 2007 she was recruited to lead the human genetics efforts of the Wellcome
Trust Sanger Center. As the distinct recognition by her peers she was
served as the President of Human Genome Organization (HUGO,
www.hugo-international.org) in 2005-2007. She was also nominated as one
of the founding members for the 22 member board of the European Research
Council (http://erc.europa.eu/). Both these nominations and her multiple
memberships in scientific advisory boards of academic institutes, genome
centers and major funding agencies worldwide reflect her leading position in
genetics and molecular medicine worldwide.
