- Cell Biology -Chromosomes, Chromatin, 3D Genome Organization, Epigenetics
- Member of Learned Society since 2019
- Title: Director, Center for Cancer Research, National Cancer Institute, National Institutes of Health, USA
NIH Distinguished Investigator
AN OVERVIEW OF RESEARCH IN THE MISTELI LABORATORY
Dr. Misteli is a pioneer in the field of genome cell biology. After completing a Master thesis in cell biology at the University of Basel, Switzerland, and a Ph.D. in biochemistry at the University of London, UK in 1995, Dr. Misteli performed post-doctoral work at Cold Spring Harbor Laboratory and joined the NIH’s National Cancer Institute (NCI) as a Tenure-track Investigator in 1999. He received tenure in 2005, was appointed Associate Director in the NCI Center for Cancer Research and was named its Director in 2016. In the same year, he was also appointed as an NIH Distinguished Investigator. Dr. Misteli is widely considered one of the world’s most pre-eminent cell biologists and in his role as the Director of the NCI Center for Cancer Research, he oversees a workforce of 3000 individuals, including 250 research groups with a budget of $450M.
In an early series of landmark studies Misteli used fluorescence photobleaching methods (FRAP) to measure the motion of DNA-binding proteins in living cells and established the now well-accepted concept of the dynamic cell nucleus (Nature, 2000a/b, 2002 Science, 2001, 2002, 2003). His laboratory also developed imaging methods to quantitatively map the location of a genome region in the 3D space of the nucleus and demonstrated that the higher order organization of the genome is non-random and differs between cell types, differentiation states, and in disease (Cell, 2007, Nature Genetics, 2003) . The latter observation has been exploited for the development of diagnostic strategies for breast and prostate cancer. These efforts in spatial genome mapping have recently culminated in the development of 3D gene mapping methods based on high-throughput imaging, which have allowed the first identification of molecular mechanisms of 3D genome organization.
Spatial genome organization is now recognized as a key contributor to physiological and pathological functions, particularly in cancer and aging. Misteli succeeded in tracking the fate of broken chromosomes in living cells and the formation of oncogenic chromosome translocations (Science, 2008, 20, Nature Cell Biology, 2007). A dramatic example of the importance of genome organization is the pre-mature aging disorder progeria, caused by a point mutation in lamin A, one of the key architectural proteins in the cell nucleus. Misteli characterized the cell biology defects of progeria patient cells and has identified several key disease pathways including most recently an anti-oxidative pathway as the primary driver in the disease (Science, 2006; Nature Medicine, 2005). These findings have inspired several therapeutic strategies for progeria. Importantly, Misteli also showed that the same pathways are also relevant for normal aging.
In sum, it has been said that Tom Misteli’s work has created the field of genome cell biology and provided the conceptual framework for mapping the genome in 3D space.
In recognition of his contributions Dr. Misteli has received numerous awards, including the 2011 Gold Medal of the First Faculty of Medicine of the Charles University, Prague, the 2012 Flemming Award, the 2013 Wilhelm Bernhard Medal, the 2016 Herman Beerman Award, and he gave a Mendel Lecture in 2018. Dr. Misteli is often invited as a keynote lecturer at professional meetings and he frequently writes opinion pieces for major scientific journals and for the lay press, including in 2011 in Scientific American. Dr. Misteli has published more than 230 original research papers and he serves on 14 scholarly editorial boards, including Cell, Science and PLOS Biology. He served as the Editor-in-Chief of The Journal of Cell Biology and is the current Editor-in-Chief of Current Opinion in Cell Biology. Dr. Misteli is a prominent member of the international cell and molecular biology community and was elected a Council member and a Fellow of the American Society for Cell Biology (ASCB).
Dr. Misteli has a long history of connection with the Czech Republic. He has visited Prague numerous times and he was invited to present lectures and presided over sessions at conferences and workshops, including EMBO workshops. When in Prague, he always managed to spend some time discussing with colleagues and students at the Institute of Cellular Biology and Pathology at the First Faculty of Medicine of Charles University, and then the Institute of Biology and Medical Genetics at the First Faculty of Medicine of Charles University and General University Hospital in Prague. Dr. Misteli received the Medal of the First Faculty of Charles University in 2011 and was honoured with a Mendel Lecture, Brno, in 2018. Dr. Misteli also hosted several Czech junior scientists in his laboratory.
The Scholarly Board of the First Faculty of Medicine of Charles University proposes to award Dr. Tom Misteli the Doctor Honoris Causa title for his life-long pioneering work in the area of genome cell biology and ground-breaking discoveries in this field as well as for his contribution to the development of international co-operation in biomedical science and support of research in the Czech Republic.
Since 2012 Director, Center for Cancer Research, NCI, NIH; NIH Distinguished Investigator Senior Deputy Director for Research, Center for Cancer Research, NCI, NIH Associate Director for Scientific Development, Center for Cancer Research, NCI, NIH; Senior Investigator, National Cancer Institute, NIH; 1999 – 2005 Tenure track investigator, NIH; Advisory Boards: Allen Institute for Cell Science; EMBO Press; American Society for Cell Biology; NIH Common Fund, Single-Cell Analysis Project; San Francisco Declaration of Research Assessment (DORA); NIH Common Fund, 4D Nucleome Planning Group; HHMI Janelia Farm; US National Academies of Sciences; European Institute of Oncology, Milan; University of Galway; Center for Chromosome Biology; Northwestern University Physical Sciences-Oncology Center; Progeria Research Foundation, Medical Advisory Board; European Union; American Federation of Aging Research; US National Academy of Sciences, Frontiers Meeting; Community activities: Co-organizer, Cold Spring Harbor Meeting “Nuclear organization & function”; Co-organizer, EMBO Workshop “Nuclear Structure and Cell Fate”; Founding Co-Chair, Gordon Research Conference “Genome Architecture in Cell Fate and Disease”; Co-organizer, ICGEB Symposium “Transcription and Splicing”, Iguazu, Argentina; Co-organizer, “Current Trends in Biomedicine” Workshop, Baeza, Spain; Public Information Committee, American Society for Cell Biology; Program Committee, Progeria Research Foundation International Symposium; Organizer, “Chromosomes, Cancer and Stem Cells”, New York Academy of Sciences. Co-author US National Academy of Science Report on “Precision Medicine”.
FELLOWSHIPS, HONORS AWARDED
2018, Mendel Lecture, Masaryk University, Brno; 2017, elected Fellow of American Society for Cell Biology; 2016, Herman Beerman Award, Society for Investigative Dermatology; 2014, Robert Feulgen Prize, Society for Histochemistry; 2013, Wilhelm Bernhard Medal; 2012, Arthur S. Flemming Award; 2011, Gold Medal of the first Faculty of Medicine, Charles University, Prague; 2011-2014 Ellison Medical Foundation Senior Scholar in Aging Award; 2010, European Research Institute, Elected Member; 2005 and 2014 NIH Director’s Award; 2003 – 2005, Keith R. Porter Fellow; 1999, Gian-Tondury Prize; 1997 – 1998, Roche Research Foundation International Fellowship Award; 1995 – 1997, HFSP Long-Term Fellowship Award; 1995, EMBO Long-Term Fellowship Award; 1994 – 1995, Swiss National Science Foundation Fellowship Award; 1991 – 1994, Imperial Cancer Research Fund Fellowship Award; Keynote Lectures: 2018, Mendel Lecture, Brno, Czech Republic; 2018 Cristofalo Lecture in Aging, University of Pennsylvania; 2017,Mayberry Lecture, Northwestern University; 2017, EADV Congress Keynote Lecture, Geneva, Switzerland; 2016, Herman Beerman Award Lecture, Scottsdale, AZ; 2016, Nobel Symposium, Stockholm, Sweden; 2015, EMBO Workshop Nuclear Dynamics, Keynote Lecture, Avignon, France; 2014, Robert Feulgen Prize Lecture, Prague, Czech Republic; 2013, Arturo Falaschi Memorial Lecture, University of Pavia, Italy; 2013, Robert Olson Memorial Lecture, St. Louis University, St. Louis; 2012, Keynote Speaker, Italian Society for Cell Biology, Ravenna, Italy; 2011, Keynote Speaker, Lorne Genome Meeting, Australia; 2010, DFG Keynote Speaker, Munich, Germany; 2009, Runnstrom Lecturer, University of Stockholm, Sweden; 2008, ASCB Plenary Speaker, San Francisco, CA; 2005, Keynote Lecturer, Kyoto University, Japan; 2005, Keynote Lecturer, International Society for Cellular Oncology, London, UK; 2003Keynote Lecturer, Norwegian Research Council, Oslo, Norway; 2002, Feulgen Lecture, International Society for Histochemistry, Vlissingen, The Netherlands; 2001, CREFSIP Lecturer, University of Quebec, Quebec, Canada.
INVITATION TO SPEAK: SYMPOSIA, SEMINARS AND SPECIAL LECTURES
More than 400.
COMMITTEES, EDITORIAL BOARDS
More than 100
REVIEWER FOR THE FOLLOWING JOURNALS
Editorial Board Memberships: Cell; Science; PLoS Biology; Biophysical Journal; Molecular Biology of the Cell; Chromosoma; Methods; Genes, Chromosomes & Cancer; Epigenetics & Chromatin (2010-2013); Transcription; Journal of Structural Biology; Journal of Cellular Physiology; Biological Procedures Online, Science Matters. In addition reviewer for (selection): Nature, Nature Genetics, Nature Structural and Molecular Biology, Nature Biotechnology, Nature Cell Biology, Nature Methods, Cell Report, Developmental Cell, Neuron, Immunity, eLife, Journal of Cell Biology, Journal of Cell Science.
American Society for Cell Biology; Whitman Society; Biophysical Society; Biochemical Society; Society for Histology.
National Cancer Institute; NIH Common Fund; Progeria Research Foundation; Ellison Medical Foundation; Department of Defence; National Science Foundation USA.
GRADUATE STUDENTS/POSTDOCTORAL FELLOWS TRAINED
Number of Predoctoral Students: 22
Number of Postdoctoral Fellows: 36
NUMBER OF CITATIONS
According to the Google Scholar: 35582
According to the Google Scholar: 92
PUBLICATIONS WITH THE HIGHEST NUMBER OF CITATIONS
- Scaffidi, P, Misteli, T. and M. Bianchi. 2002. The release of chromatin protein HMGB1 from necrotic cells triggers inflammation. Nature. 418, 191-195; citations: 3548
- Phair, R. D. and T. Misteli, 2000. High mobility of proteins in the mammalian cell nucleus. Nature. 404, 604-609; citations: 1152
- Misteli, T. 2007. Beyond the sequence: Cellular organization of genome function. Cell. 128, 787-800; citations: 1016
- Poulikakos, P., Persaud, Y., Janakiraman, M., Kong, X., Ng, C. , Moriceau, G. , Shi, H., Atefi, M., Titz, B., Gabay, M., Salton. M, Dahlman, K., Tadi, M., Wargo, J., Flaherty, K. , Kelley. M., Misteli, T. et al. 2011. RAF inhibito resistance is mediated by splicing isoforms of BRAF(V600E) that dimerize in a RAS-independent manner. Nature. 480, 387-390; citations: 998
- Meshorer, E., D. Yellajoshula, E. George, P. J. Scambler, D.T. Brown and T. Misteli, 2006. Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells. Dev. Cell. 10, 105-116; citations: 894
- Scaffidi, P. and T. Misteli. 2006. Lamin-A dependent nuclear defects in human aging. Science. 312, 1059-1063; citations: 819
- Luco, R.F., Pan, Q., Tominaga, K., Blencowe, B.J., Perreira-Smith, O.M., and T. Misteli. 2010. Regulation of alternative splicing by histone modifications. Science. 327, 996-1000; citations: 774
- Misteli, T. 2001. Protein dynamics: Implications for nuclear architecture and gene expression. Science. 291, 843-847; citations: 703
- Misteli, T., Gunjan, A., Hock, R., Bustin, M. and D. Brown, 2000. Dynamic binding of linker histone H1 to chromatin in living cells. Nature. 408, 877-881; citations: 609
- Meshorer, E and T. Misteli, 2006. Chromatin in pluripotent embryonic stem cells and differentiation. Nature Rev. Mol. Cell Biol. 7, 540-546; citations: 631
10 MOST RECENT PUBLICATIONS
- Jowhar, Z., Gudla, R., Shachar, S., Wangsa, D., Russ, J.L., Pegoraro, G., Ried, T., Raznahan, A., and T. Misteli. 2018. HiCTMap: Detection and Analysis of Chromosome Territory Structure and Position by High-throughput Imaging. Methods. 142, 30-38
- Baranes-Bachar, K., Levy-Barda, E., Oehler, J., Reid, D.A., Soria-Bretones, I., Voss, T.C., Chung, D., Par, Y., Liu, C., Yoon, J.B, Li, W., Dellaire, G., Misteli, T., Huertas, P., Rothenberg, E., Ramadan, K., Ziv, Y. and Y. Shiloh. 2018. Molecular Cell. 69, 866-878
- Serebryannyy, L. and T. Misteli. 2018. Protein sequestration at the nuclear periphery as a potential regulatory mechanism in pre-mature aging. J. Cell Biol., 217, 21-37
- Gudla, P., Nakayama, K., Pegoraro, G. and T. Misteli. 2017. SpotLearn: Convolutional Neural Network for Detection of Fluorescence In Situ Hybridization (FISH) Signals in High-Throughput Imaging Approaches, Cold Spring Harbor Symp. Quant. Biol. 82, 57-70
- DeBoy, E., Puttaraju, M., Jailwala, P., Kasoji, M., Cam., M. and T. Misteli. 2017. Identification of novel RNA isoforms of LMNA. Nucleus. 8, 573-582
- Padmanabhan, S., Misteli, T. and D.L. DeVoe. 2017. Controlled droplet discretization and manipulation using membrane displacement traps. Lab on Chip, 17, 3717-3724
- Dekker, J, 4D Nucleome Network. T. Misteli et al. 2017. The 4D Nucleome Project. Nature. 535:575-579
- Kubben, N. and T. Misteli. 2017. Shared Molecular and Cellular Roots of Premature Ageing and Ageing-Associated Diseases. Nature Reviews Mol. Cell Biol. 18:595-609.
- Larson, D.R. and T. Misteli. 2017. The genome - seeing it clearly now. Science. 357, 354-355
- Kieffer-Kwon, K.R., Misteli, T. et al. 2017. Myc regulates chromatin decompaction and nuclear architecture during B cell activation. Molecular Cell. 67, 566-578