Eric Schadt Explained

Eric Schadt
Birth Date:31 January 1965
Birth Place:St. Joseph, Michigan, United States
Work Institutions:
Sema4
Icahn School of Medicine at Mount Sinai
Sage Bionetworks
Alma Mater:California Polytechnic State University
University of California, Davis
University of California, Los Angeles

Eric Emil Schadt (born January 31, 1965) is an American mathematician and computational biologist. He is founder and former chief executive officer of Sema4, a patient-centered health intelligence company, and dean for precision medicine and Mount Sinai Professor in Predictive Health and Computational Biology at the Icahn School of Medicine at Mount Sinai. He was previously founding director of the Icahn Institute for Genomics and Multiscale Biology and chair of the Department of Genetics and Genomics Sciences at the Icahn School of Medicine at Mount Sinai.

Schadt's work combines supercomputing and advanced computational modeling with diverse biological data to understand the relationship between genes, gene products, other molecular features such as cells, organs, organisms, and communities and their impact on complex human traits such as disease.[1] He is known for calling for a shift in molecular biology toward a network-oriented view of living systems to complement the reductionist, single-gene approaches that currently dominate biology to more accurately model the complexity of biological systems.[2] [3] Schadt has also worked to engage the public, encouraging people to participate in scientific research and helping them understand privacy concerns around DNA-based information.[4] [5]

Research and training

In 1983, Schadt left high school early to enlist in the United States Air Force and joined a Special Operations/Rescue unit. After sustaining a serious shoulder injury that required reconstructive surgery, Schadt attended California Polytechnic State University on a military scholarship to study computer science and mathematics, and received his bachelor's degree in applied mathematics in 1991.[1] He went on to earn a master's degree in pure mathematics at the University of California, Davis in 1993. After that, he pursued a PhD in biomathematics at the University of California, Los Angeles, which required PhD candidacy in both molecular biology and biomathematics, completing his doctorate under the supervision of Ken Lange in 2000.[3] During his PhD work, Schadt worked as a senior software engineer at the UCLA Office of Academic Computing and later as director of computing in the UCLA mathematical sciences department.

Scientific career

Early career

While completing his PhD, Schadt joined Roche Bioscience in 1998 as a senior research scientist and began his work on DNA microarrays, designing novel algorithms to process and interpret these data. He published some of the first independently developed algorithms to process gene chip data[6] [7] work that he later applied to produce an early whole genome functional annotation of the human genome.[8]

In 1999, after becoming acquainted with Stephen Friend, he was hired as chief scientist at Rosetta Inpharmatics, a startup biotech company focused on the generation and analysis of high-dimensional functional genomics data.[1] Merck acquired Rosetta in 2001, which allowed Schadt to combine large-scale molecular profiling with Merck's disease-focused databases to demonstrate the existence of molecular networks working together to give rise to complex system behavior.[9] [10] During this period Schadt developed his theory that single-gene approaches to understanding and treating common human diseases must give way to a network-based approach and that many of the failures in pharmaceutical therapies were caused by an incomplete understanding of biology underlying the therapeutic targets.[2]

Demonstrating the ability to infer causal relationships among features in high dimensional data using DNA variation information, Schadt and his colleagues at Merck began reconstructing predictive networks that were shown to be causally associated with disease,[11] [12] [13] [14] [15] leading to the idea of targeting networks, not single genes, to effectively treat common disorders such as Alzheimer's disease, obesity, and most forms of cancer.[16] A Merck spokesman said that the papers Schadt began publishing based on this genetic network data “changed the way people looked at disease.” Schadt used the information about these networks to determine which genes Merck should pursue as targets; by the time he left the company, Schadt estimated that his group was responsible for half the drugs in the company's development pipeline.[1]

In 2009, along with Stephen Friend, Schadt founded Sage Bionetworks,[3] a nonprofit organization with the goal of encouraging collaboration between academic and commercial scientists in performing network-based studies of disease and making the data publicly available. When Merck closed down the Rosetta business unit, it donated the data, research, and computer equipment from that unit to Sage Bionetworks.[1] Schadt remains involved as a board member.[17]

Also in 2009, Schadt joined DNA sequencing company Pacific Biosciences as the chief scientific officer. During his time there, Schadt demonstrated the application of SMRT sequencing technology for various applications,[18] including to sequence bacterial genomes of public health concern to provide real-time information about these pathogenic strains during an active outbreak. He led research projects to resolve the origins of the Haitian cholera outbreak strain from 2010[19] and to characterize the highly virulent German E. coli outbreak strain in the summer of 2011.[20] He also demonstrated the ability to infer epigenetic changes from the sequencing data, uncovering novel regulatory mechanisms that may impact pathogenicity and virulence of bacteria of concern in public health.[21] [22]

Mount Sinai

In 2011, Schadt joined the Mount Sinai School of Medicine in New York, where he founded the new Icahn Institute for Genomics and Multiscale Biology and became chair of the Department of Genetics and Genomics Sciences.[23] [24] [25] The new institute was launched with $100 million for the first five years and is co-directed by Andrew Kasarskis.[25] Schadt has said that his interest in joining Mt. Sinai was to bring predictive modeling of biology to patients. In his time at the institute, he has opened the first CLIA-certified next-generation sequencing lab in New York City[26] and established the first class at the school in which students sequence their own genomes.[27] [28] Schadt also serves on the executive committee of the New York Genome Center.

In 2013, Schadt and his team were awarded a grant from the National Institutes of Health to study biological networks in Alzheimer's disease.[29] They also published a paper in Cell reporting that a network of genes linked to inflammatory response plays a role in late-onset Alzheimer's disease.[30] [31] Also that year, Schadt joined the Cure Alzheimer's Fund's Research Consortium along with Richard L. Huganir.

Schadt's team was cited as the reason the Icahn School of Medicine at Mount Sinai was named #5 of the top 10 most innovative organizations in big data by Fast Company in a 2014 ranking.[32] According to the article, "The New York City hospital is bringing on top Silicon Valley talent to build a facility that will map patients’ genomes to predict diseases, reduce the number of average hospital visits, and streamline electronic medical records."

In May 2014, Schadt and his team announced the Resilience Project in collaboration with Sage Bionetworks.[33] The project intended to perform genotyping on as many as 1 million people to find protective biological mechanisms that prevent disease-causing genetic mutations from becoming active. Participants were to be healthy people age 30 and older, and the project initially targeted variations linked to 127 Mendelian diseases.[34] [35] Based on an analysis of publicly available data, scientists in the Resilience Project estimated that one person in 15,000 has a protective mechanism preventing activity of disease-causing genetic variants.[36] The project led to a paper published in 2016 in Nature Biotechnology, reporting the analysis of nearly 600,000 genomes and the identification of individuals resilient to severe Mendelian childhood diseases.

Sema4

Schadt founded Sema4, "a patient-centered health intelligence company dedicated to advancing healthcare through data-driven insights,"[37] in June 2017.[38] The company uses Centrellis™, their health analytics platform, to build predictive models of human health and generate personalized medicine insights.[37] Sema4, which was named one of the 150 most promising private digital health companies in the world by CB Insights in its 2020 Digital Health 150 ranking,[39] operates two state-of-the art clinical laboratories in Connecticut, including a 70,000-square-foot facility opened in December 2020[40] The company announced in February 2021 that it would be going public through a merger with CM Life Sciences, a special purpose acquisition company (SPAC).[41]

Media appearances and awards

Schadt has appeared on CNN, CNBC, BBC, Bloomberg Radio, and Bloomberg TV.[42] He and his scientific projects have been profiled in the New York Times, Esquire magazine,[2] Bloomberg BusinessWeek,[43] among others,[44] and several scientific trade publications. The Huffington Post published a commentary by Schadt, calling on scientists to incorporate information about RNA, proteins, metabolites and more into their genetic or clinical research, while asking the public to participate in research projects to help speed scientific discovery.[45] Schadt has also spoken at numerous events including TEDMED, the health/medicine edition of the world-famous TED conference.

He has received many awards, including the Thomson Reuters World's Most Influential Scientific Minds Award[46] and the Merck Presidential Fellowship Award. He was executive producer and creative director of a documentary film called “The New Biology” that won a Cine Master Series Award in 2012.[47] In 2020, Schadt was named the BioCT Entrepreneur of the Year.[48]

Selected publications

Schadt has published more than 370 peer-reviewed papers.[49] He is a highly cited author, with an h-index of 129 and more than 145,500 citations.[50] Some notable publications include:

Notes and References

  1. News: David Ewing Duncan . Enlisting Computers to Unravel the True Complexity of Disease . . 2009-08-24 . 2017-06-17.
  2. Web site: Junod . Tom . Eric Schadt Profile - Interview with Eric Schadt Pacific Biosciences . Esquire.com . 2011-03-22 . 2017-06-17.
  3. Web site: The Schadt Equation | GEN . Genengnews.com . 2013-01-15 . 2017-06-17.
  4. Schadt EE. 2012. The changing privacy landscape in the era of big data. Molecular Systems Biology. 8. 612. 10.1038/msb.2012.47. 22968446. 3472686.
  5. Web site: "Genetic Heroes" May Be Key to Treating Debilitating Diseases . Scientific American . 2014-05-30 . 2017-06-17.
  6. Schadt, E. E.. Li, C.. Su, C.. Wong, W. H.. Analyzing high-density oligonucleotide gene expression array data. . Journal of Cellular Biochemistry . 80. 2. 192–202 . 2000. 10.1002/1097-4644(20010201)80:2<192::aid-jcb50>3.3.co;2-n. 11074587.
  7. Schadt, E. E.. Li, C.. Su, C.. Wong, W. H.. Feature extraction and normalization algorithms for high-density oligonucleotide gene expression array data. Journal of Cellular Biochemistry. Supplement Suppl 37. 120–125. 2001. 10.1002/jcb.10073. 11842437. 6810381.
  8. Shoemaker, D. D.. etal. Experimental annotation of the human genome using microarray technology. Nature . 409. 6822. 922–927. 10.1038/35057141 . 11237012. 2001. 2001Natur.409..922S. 2509337. free.
  9. Schadt, E. E.. etal. Genetics of gene expression surveyed in maize, mouse and man. Nature. 422. 6929. 297–302. 10.1038/nature01434. 12646919. 2003. 2003Natur.422..297S. 2559717.
  10. Schadt, E. E.. Monks, S. A.. Friend, S. H.. A new paradigm for drug discovery: integrating clinical, genetic, genomic and molecular phenotype data to identify drug targets. Biochemical Society Transactions. 31. 2. 437–443. 2003. 10.1042/bst0310437. 12653656. 2013-01-30. https://archive.today/20130414123524/http://test.biochemsoctrans.org/bst/031/0437/bst0310437.htm. 2013-04-14. dead.
  11. Schadt, E. E.. Sachs, A.. Friend, S.. Embracing complexity, inching closer to reality. Science's STKE. 2005. 40. 10.1126/stke.2952005pe40 . 16077086. 2005. 295. 23744520.
  12. Chen, Y.. etal. Variations in DNA elucidate molecular networks that cause disease. Nature . 452. 7186. 429–435. 10.1038/nature06757 . 18344982. 2008. 2841398. 2008Natur.452..429C.
  13. Emilsson, V.. etal. Genetics of gene expression and its effect on disease. Nature. 452. 7186. 423–428. 10.1038/nature06758. 18344981. 2008. 2008Natur.452..423E. 1219108.
  14. Schadt, E. E.. Molecular networks as sensors and drivers of common human diseases. Nature. 461. 7261. 218–223. 10.1038/nature08454 . 19741703. 2009. 2009Natur.461..218S. 4323333.
  15. Yang, X.. etal. Validation of candidate causal genes for obesity that affect shared metabolic pathways and networks. Nature Genetics. 41. 4. 415–423. 10.1038/ng.325 . 19270708. 2009. 2837947.
  16. Schadt, E. E.. Friend, S. H.. Shaywitz, D. A. . A network view of disease and compound screening. Nature Reviews Drug Discovery. 8. 4. 286–295. 10.1038/nrd2826. 19337271. 2009. 21562023.
  17. Web site: Sage Bionetworks Seattle | Directors . 2013-01-30 . dead . https://web.archive.org/web/20120127081638/http://sagebase.org/info/directors.php . 2012-01-27 .
  18. Schadt, E. E.. Turner, S.. Kasarskis, A.. A window into third-generation sequencing. Human Molecular Genetics . 19. R2. 10.1093/hmg/ddq416 . 20858600. 2010. R227–R240. free.
  19. Chin, C. S.. etal. The origin of the Haitian cholera outbreak strain. The New England Journal of Medicine . 364. 1. 33–42. 10.1056/NEJMoa1012928 . 21142692. 2011. 3030187.
  20. Rasko, D. A.. etal. Origins of the E. coli strain causing an outbreak of hemolytic-uremic syndrome in Germany. . The New England Journal of Medicine. 365. 8. 709–717. 10.1056/NEJMoa1106920 . 21793740. 2011. 3168948.
  21. Fang, G.. etal. Genome-wide mapping of methylated adenine residues in pathogenic Escherichia coli using single-molecule real-time sequencing. Nature Biotechnology. 30. 12. 1232–1239. 10.1038/nbt.2432 . 23138224. 3879109. 2012.
  22. Schadt, E. E.. etal. Modeling kinetic rate variation in third generation DNA sequencing data to detect putative modifications to DNA bases. . 23. 1. 129–141. 10.1101/gr.136739.111. 23093720. 2013. Genome Research. 3530673.
  23. Web site: Eric Schadt, PhD, Named Director of Institute for Genomics and Multiscale Biology at The Mount Sinai Medical Center - Icahn School of Medicine at Mount Sinai . Mssm.edu . 2017-06-17.
  24. Web site: PacBio CSO Eric Schadt to Lead 'Multiscale Institute' at Mount Sinai - Bio-IT World . 2013-01-30 . dead . https://web.archive.org/web/20110730165839/http://www.bio-itworld.com/news/05/16/2011/PacBio-CSO-Eric-Schadt-Lead-Multiscale-institute-Mt-Sinai.html . 2011-07-30 .
  25. Web site: Eric Schadt of Pacific Biosciences Joins Mount Sinai - NYTimes.com . 2013-01-30 . dead . https://web.archive.org/web/20130224130451/http://prescriptions.blogs.nytimes.com/2011/05/16/schadt-joins-mount-sinai-medical-school/ . 2013-02-24 .
  26. Eric Schadt . 10.1038/nbt.2331. 22871721 . 30. 8 . 2012. Nature Biotechnology. 769–770. Schadt . E. . free.
  27. Web site: Q&A: Mount Sinai's Andrew Kasarskis on Teaching Students how to Analyze their Own Genomes . GenomeWeb.com . 2012-10-24 . 2017-06-17.
  28. Web site: Genomics annual report fnl by Mount Sinai Health System . Issuu.com . 2014-05-02 . 2017-06-17.
  29. Web site: NIH funding boosts new Alzheimer's research on prevention, novel drug targets | National Institutes of Health (NIH) . Nih.gov . 2013-09-18 . 2017-06-17.
  30. Web site: Cell - Integrated Systems Approach Identifies Genetic Nodes and Networks in Late-Onset Alzheimer's Disease . www.cell.com . 27 January 2022 . https://archive.today/20130713030433/http://www.cell.com/abstract/S0092-8674(13)00387-5 . 13 July 2013 . dead.
  31. Web site: Gene Studies Could Point to New Alzheimer's Treatments - US News . 2014-08-18 . dead . https://web.archive.org/web/20140819083406/http://health.usnews.com/health-news/news/articles/2013/04/25/gene-studies-could-point-to-new-alzheimers-treatments . 2014-08-19 .
  32. Web site: The Most Innovative Companies of 2014 by Sector . Fast Company . 2017-06-17.
  33. Friend . Stephen H. . Clues from the resilient | Science . Science . 2014-05-30 . 344 . 6187 . 970–972 . 10.1126/science.1255648 . 24876479 . 26492504 . 2017-06-17.
  34. Web site: The Search for Genes That Prevent Disease . . 2014-05-29 . 2017-06-17.
  35. Web site: The Resilience Project | Join the Search. Be a Hero . Resilienceproject.me . 2016-04-11 . 2017-06-17.
  36. Web site: Searching For The Hidden Health Heroes Whose DNA Prevents Disease . Fastcoexist.com . 2014-05-29 . 2017-06-17.
  37. Web site: Our Story . Sema4.com . 2021-04-12.
  38. Web site: Introducing Sema4: A Spinout Company of the Mount Sinai Health System Mount Sinai - New York. 2021-03-16. Mount Sinai Health System. en-US.
  39. Web site: Sema4 Named to the 2020 CB Insights Digital Health 150, a List of the Most Innovative Digital Health Startups. 2021-04-20.
  40. Web site: Sema4 opens 70,000-square-foot clinical lab in Stamford . 3 December 2020 . 2021-04-12.
  41. Web site: Sema4 to Go Public Through Merger With Special Purpose Acquisition Company. 2021-03-16. GenomeWeb. 10 February 2021 . en-us.
  42. Web site: How the iPhone is Helping Doctors Battle Diseases . Bloomberg.com. 11 March 2015 .
  43. Web site: Icahn Institute's Eric Schadt on Data Analysis in Medicine - Bloomberg . https://archive.today/20140815134800/http://www.businessweek.com/articles/2014-03-06/icahn-institutes-eric-schadt-on-data-analysis-in-medicine . dead . August 15, 2014 . Businessweek.com . 2014-03-06 . 2017-06-17.
  44. Web site: The little girl who may hold the secret to aging . Macleans.ca . 2014-07-20 . 2017-06-17.
  45. Web site: It's Not Just the Genes | HuffPost . Huffingtonpost.com . 24 October 2013. 2017-06-17.
  46. Web site: The World's Most Influential Scientific Minds . 2014 . Sciencewatch.com . 2017-06-17.
  47. Web site: Archived copy . 2013-01-30 . dead . https://web.archive.org/web/20130120151951/http://www.johnrubin.com/images/jd_cv.pdf . 2013-01-20 .
  48. Web site: Eric Schadt, Founder & CEO of Sema4, Named 2020 BioCT Entrepreneur of the Year . 2021-04-12.
  49. Web site: schadt, ee - search results . PubMed . 2021-04-20.
  50. Web site: Eric Schadt - Google Scholar . 2021-04-20.
  51. Schadt, E. E.. etal. An integrative genomics approach to infer causal associations between gene expression and disease. Nature Genetics. 37. 7. 710–717. 10.1038/ng1589. 15965475. 2841396. 2005.
  52. + See all authors and affiliations . The Runners-Up | Science . Science . 2005-12-23 . 310 . 5756 . 1880–1885 . 10.1126/science.310.5756.1880a . 16373539 . 32119689 . 2017-06-17.
  53. Califano A. Butte AJ. Friend S. Ideker T. Schadt EE. 2012. Integrative Network-based Association Studies: Leveraging cell regulatory models in the post-GWAS era. Nature Genetics. 44 . 8. 841–847. 10.1038/ng.2355. 22836096. 3593099.
  54. A functional genomics predictive network model identifies regulators of inflammatory bowel disease . 2017. 28892060. Peters. L. A.. Perrigoue. J.. Mortha. A.. Iuga. A.. Song. W. M.. Neiman. E. M.. Llewellyn. S. R.. Di Narzo. A.. Kidd. B. A.. Telesco. S. E.. Zhao. Y.. Stojmirovic. A.. Sendecki. J.. Shameer. K.. Miotto. R.. Losic. B.. Shah. H.. Lee. E.. Wang. M.. Faith. J. J.. Kasarskis. A.. Brodmerkel. C.. Curran. M.. Das. A.. Friedman. J. R.. Fukui. Y.. Humphrey. M. B.. Iritani. B. M.. Sibinga. N.. Tarrant. T. K.. Nature Genetics. 49. 10. 1437–1449. 10.1038/ng.3947. 5660607. 1.