Paul Salomon Mischel | |
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Born | Syracuse, NY, USA. | July 13, 1962
Education | |
Known for | Extrachromosomal DNA in cancer (ecDNA) |
Relatives | Doborah Kado, M.D. Walter Mischel |
Awards | National Academy of Medicine Ernst W. Bertner Prize for Distinbuished Contributions to Cancer Research ContentsAmerican Society for Clinical Investigation (President, 2010/2011) American Association of Physicians Fellow, American Association for the Advancement of Science |
Scientific career | |
Fields | Cancer genetics and pathology |
Institutions | Stanford University, University of California, San Diego, University of California, Los Angeles |
Website | Group Website Google Scholar |
Paul S. Mischel (born July 13, 1962) is a physician-scientist whose laboratory has made pioneering discoveries in the pathogenesis of human cancer [1] . He is the Fortinet Founders Professor, and Vice Chair for Research for the Department of Pathology, Stanford Medicine, an Institute Scholar in Sarafan ChEM-H. He is also a Faculty Advisor for Experimental Biology at the Innovative Medicines Accelerator at Stanford University. Mischel’s research published in a series of papers in Nature and Science, has catalyzed a paradigm shift in precision oncology that promises to transform the diagnosis and treatment of patients suffering from some of the most aggressive forms of cancer [2] .
Mischel was born on July 13, 1962. After losing his father to cancer, he became committed to a career in cancer research. He attended the University of Pennsylvania and received his M.D. from Cornell University Medical College in 1991, graduating Alpha Omega Alpha. Mischel completed residency training in Anatomic Pathology and Neuropathology at UCLA, followed by post-doctoral research training with Louis Reichardt at HHMI-UCSF. Mischel joined the faculty of UCLA in 1998. In August 2012, he was recruited to the Ludwig Institute for Cancer Research, San Diego and UCSD. In 2021, he joined Stanford University School of Medicine, where he currently serves as a Professor and Vice Chair of Research for the Department of Pathology and Institute Scholar of ChEM-H. Mischel leads the team of eDyNAmiC project.
Mischel’s research has demonstrated a central role for ecDNA in cancer. Studies he has led, published in a series of papers in Nature and Science, has provided a mechanistic understanding of the molecular basis of intratumoral genetic heterogeneity, accelerated evolution and treatment resistance driven by ecDNA oncogene amplification. His team’s research has shown that ecDNA occurs in close to 20% of all solid cancers, of women and men, children and adults, that it is associated with poor outcome for patients. This research has revealed clinical implications and underlying molecular mechanisms of ecDNA in cancer development and progression, suggesting the potential for future ecDNA-directed cancer treatments [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] .
Mischel is a member of the National Academy of Medicine [15] and recipient of the Ernst W. Bertner Memorial Award from MD Anderson for Distinguished Contributions to Cancer Research. Mischel is also an elected Fellow and Past-President of the American Society for Clinical Investigation, and an elected Fellow of the American Association of Physicians and The American Association for the Advancement of Science.
Mischel is married to Professor Deborah Kado, Chief of Geriatrics Research, co-director of the Stanford Longevity Center, and Director of the Palo Alto VA Geriatrics Research, Education, and Clinical Center. They have two daughters, Dr. Anna Mischel and Dr. Sarah Mischel. Paul is the son of the cognitive philosopher Theodore Mischel and the nephew of the famed psychologist, Walter Mischel.
Gene duplication is a major mechanism through which new genetic material is generated during molecular evolution. It can be defined as any duplication of a region of DNA that contains a gene. Gene duplications can arise as products of several types of errors in DNA replication and repair machinery as well as through fortuitous capture by selfish genetic elements. Common sources of gene duplications include ectopic recombination, retrotransposition event, aneuploidy, polyploidy, and replication slippage.
Double minutes (DMs) are small fragments of extrachromosomal DNA, which have been observed in a large number of human tumors including breast, lung, ovary, colon, and most notably, neuroblastoma. They are a manifestation of gene amplification as a result of chromothripsis, during the development of tumors, which give the cells selective advantages for growth and survival. This selective advantage is as a result of double minutes frequently harboring amplified oncogenes and genes involved in drug resistance. DMs, like actual chromosomes, are composed of chromatin and replicate in the nucleus of the cell during cell division. Unlike typical chromosomes, they are composed of circular fragments of DNA, up to only a few million base pairs in size, and contain no centromere or telomere. Further to this, they often lack key regulatory elements, allowing genes to be constitutively expressed. The term ecDNA may be used to refer to DMs in a more general manner. The term Double Minute originates from the visualization of these features under microscope; double because the dots were found in pairs, and minute because they were minuscule.
Extrachromosomal DNA is any DNA that is found off the chromosomes, either inside or outside the nucleus of a cell. Most DNA in an individual genome is found in chromosomes contained in the nucleus. Multiple forms of extrachromosomal DNA exist, and, while some of these serve important biological functions, they can also play a role in diseases such as cancer.
In molecular biology, SWI/SNF, is a subfamily of ATP-dependent chromatin remodeling complexes, which is found in eukaryotes. In other words, it is a group of proteins that associate to remodel the way DNA is packaged. This complex is composed of several proteins – products of the SWI and SNF genes, as well as other polypeptides. It possesses a DNA-stimulated ATPase activity that can destabilize histone-DNA interactions in reconstituted nucleosomes in an ATP-dependent manner, though the exact nature of this structural change is unknown. The SWI/SNF subfamily provides crucial nucleosome rearrangement, which is seen as ejection and/or sliding. The movement of nucleosomes provides easier access to the chromatin, enabling binding of specific transcription factors, and allowing genes to be activated or repressed.
Haplogroup pre-JT is a human mitochondrial DNA haplogroup (mtDNA). It is also called R2'JT.
The National Astronomical Observatories, Chinese Academy of Sciences(NAOC, Chinese: 中国科学院国家天文台; pinyin: Zhōngguó Kēxuéyuàn Guójiā Tiānwéntái) is an astronomical research institute operated by the Chinese Academy of Sciences, along with Shanghai Astronomical Observatory, Purple Mountain Observatory and National Time Service Center.
Haplogroup HIJK, defined by the SNPs F929, M578, PF3494 and S6397, is a common Y-chromosome haplogroup. Like its parent macrohaplogroup GHIJK, Haplogroup HIJK and its subclades comprise the vast majority of the world's male population.
Extrachromosomal circular DNA (eccDNA) is a type of double-stranded circular DNA structure that was first discovered in 1964 by Alix Bassel and Yasuo Hotta. In contrast to previously identified circular DNA structures, eccDNA are circular DNA found in the eukaryotic nuclei of plant and animal cells. Extrachromosomal circular DNA is derived from chromosomal DNA, can range in size from 50 base pairs to several mega-base pairs in length, and can encode regulatory elements and full-length genes. eccDNA has been observed in various eukaryotic species and it is proposed to be a byproduct of programmed DNA recombination events, such as V(D)J recombination.
Bik Kwoon Yeung Tye is a Chinese-American molecular geneticist and structural biologist. Tye's pioneering work on eukaryotic DNA replication led to the discovery of the minichromosome maintenance (MCM) genes in 1984, which encode the catalytic core of the eukaryotic replisome. Tye also determined the first high-resolution structures of both the MCM complex and the Origin Recognition Complex (ORC) in 2015 and 2018. Tye is currently a Professor Emeritus (2015) at Cornell University and a visiting professor at the Hong Kong University of Science & Technology. She is married to Henry Sze-Hoi Tye and is the mother of Kay Tye and Lynne Tye.
Julie Law is an American molecular and cellular biologist. Law's pioneering work on DNA methylation patterns led to the discovery of the role of the CLASSY protein family in DNA methylation. Law is currently an associate professor at the Salk Institute for Biological Studies.
Cancer Likelihood in Plasma (CLiP) refers to a set of ensemble learning methods for integrating various genomic features useful for the noninvasive detection of early cancers from blood plasma. An application of this technique for early detection of lung cancer (Lung-CLiP) was originally described by Chabon et al. (2020) from the labs of Ash Alizadeh and Max Diehn at Stanford.
Vishva Mitra Dixit is a Kenyan-American physician who is currently Vice President and Senior Fellow of Physiological Chemistry and Research Biology at Genentech.
Edward Francis Fritsch is a scientist in the field of molecular biology and cancer immunology.
Jan Karlseder an Austrian molecular biologist, is the Chief Science Officer and a Senior Vice President at the Salk Institute for Biological Studies. He is also a professor in the Molecular and Cellular Biology Laboratory, the Director of the Paul F. Glenn Center for Biology of Aging Research and the holder of the Donald and Darlene Shiley Chair at the Salk Institute for Biological Studies.
Colibactin is a genotoxic metabolite produced by Escherichia coli and other Enterobacteriaceae believed to cause mutations leading to colorectal cancer and the progression of colorectal cancer. Colibactin is a polyketide peptide that can form interstrand crosslinks in DNA. Colibactin is only produced by bacterial strains containing a polyketide synthase genomic island (pks) or clb biosynthetic gene cluster. About 20% of humans are colonized with E. coli that harbor the pks island.
In photonics, a meta-waveguide is a physical structures that guides electromagnetic waves with engineered functional subwavelength structures. Meta-waveguides are the result of combining the fields of metamaterials and metasurfaces into integrated optics. The design of the subwavelength architecture allows exotic waveguiding phenomena to be explored.
Christina Curtis is an American scientist who is a Professor of Medicine, Genetics and Biomedical Data Science and an Endowed Scholar at Stanford University where her research investigates the evolution of tumors. She is director of Artificial Intelligence and Cancer Genomics at Stanford University School of Medicine and is on the board of directors of the American Association for Cancer Research.
The Fanzor (Fz) protein is an eukaryotic, RNA-guided DNA endonuclease, which means it is a type of DNA cutting enzyme that uses RNA to target genes of interest. It has been recently discovered and explored in a number of studies. In bacteria, RNA-guided DNA endonuclease systems, such as the CRISPR/Cas system, serve as an immune system to prevent infection by cutting viral genetic material. Currently, CRISPR/Cas9-mediated's DNA cleavage has extensive application in biological research, and wide-reaching medical potential in human gene editing.
Circular consensus sequencing (CCS) is a DNA sequencing method that is used in conjunction with single-molecule real-time sequencing to yield highly accurate long-read sequencing datasets with read lengths averaging 15–25 kb with median accuracy greater than 99.9%. These long reads, which are created via the formation of consensus sequencing obtained from multiple passes on a single DNA molecule, can be used to improve results for complex applications such as single nucleotide and structural variant detection, genome assembly, assembly of difficult polyploid or highly repetitive genomes, and assembly of metagenomes.
Ning Zheng is an experimental structural biologist and protein biochemist known for his pioneering work in the fields of molecular glues and targeted protein degradation. He is currently a professor in the Department of Pharmacology at the University of Washington School of Medicine and a Howard Hughes Medical Institute (HHMI) Investigator.
Team eDyNAmiC: Following the science and accelerating our understanding of ecDNA
Cracking the code of DNA circles in cancer, Stanford Medicine-led team uncovers potential therapy
Study raises hopes of treating aggressive cancers by zapping rogue DNA
Coming full circle with extrachromosomal DNA, cancer and Ptolemy
Cancers cheat during mitosis to pass on their most malignant genes