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Eric Schadt

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Eric Schadt
Born (1965-01-31) January 31, 1965 (age 59)
St. Joseph, Michigan, United States
Alma materCalifornia Polytechnic State University
University of California, Davis
University of California, Los Angeles
Scientific career
Institutions
Sema4
Icahn School of Medicine at Mount Sinai
Sage Bionetworks

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

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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[citation needed].

Scientific career

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Early career

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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

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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

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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

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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

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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:

  • A Nature Genetics paper[51] that was selected by Science as one of the top 10 breakthroughs of the year in 2005.[52]
  • The first publication linking a full-genome scan of methylation to a genome sequence for the E. coli microbe.[21]
  • One of the earliest publications using microarrays to annotate the human genome.[8]
  • An editorial in Molecular Systems Biology on privacy concerns in the genome era calling for improved education of legislators, expanded non-discrimination laws, and protection of patients' rights.[4]
  • A publication in Nature Genetics predicting a shift from genome-wide association studies to integrative, network-based association studies (INAS) that take into account more types of biological data in order to discern the cause of variation in traits and diseases.[53]
  • A 2017 Nature Genetics paper reporting the use of functional genomics predictive network models to identify regulators of inflammatory bowel disease (IBD).[54]

References

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  1. ^ a b c d e David Ewing Duncan (2009-08-24). "Enlisting Computers to Unravel the True Complexity of Disease". The New York Times. Retrieved 2017-06-17.
  2. ^ a b c Junod, Tom (2011-03-22). "Eric Schadt Profile - Interview with Eric Schadt Pacific Biosciences". Esquire.com. Retrieved 2017-06-17.
  3. ^ a b c "The Schadt Equation | GEN". Genengnews.com. 2013-01-15. Retrieved 2017-06-17.
  4. ^ a b Schadt EE (2012). "The changing privacy landscape in the era of big data". Molecular Systems Biology. 8: 612. doi:10.1038/msb.2012.47. PMC 3472686. PMID 22968446.
  5. ^ ""Genetic Heroes" May Be Key to Treating Debilitating Diseases". Scientific American. 2014-05-30. Retrieved 2017-06-17.
  6. ^ Schadt, E. E.; Li, C.; Su, C.; Wong, W. H. (2000). "Analyzing high-density oligonucleotide gene expression array data" (PDF). Journal of Cellular Biochemistry. 80 (2): 192–202. doi:10.1002/1097-4644(20010201)80:2<192::aid-jcb50>3.3.co;2-n. PMID 11074587.
  7. ^ Schadt, E. E.; Li, C.; Su, C.; Wong, W. H. (2001). "Feature extraction and normalization algorithms for high-density oligonucleotide gene expression array data" (PDF). Journal of Cellular Biochemistry. Supplement Suppl 37: 120–125. doi:10.1002/jcb.10073. PMID 11842437. S2CID 6810381.
  8. ^ a b Shoemaker, D. D.; et al. (2001). "Experimental annotation of the human genome using microarray technology" (PDF). Nature. 409 (6822): 922–927. Bibcode:2001Natur.409..922S. doi:10.1038/35057141. PMID 11237012. S2CID 2509337.
  9. ^ Schadt, E. E.; et al. (2003). "Genetics of gene expression surveyed in maize, mouse and man". Nature. 422 (6929): 297–302. Bibcode:2003Natur.422..297S. doi:10.1038/nature01434. PMID 12646919. S2CID 2559717.
  10. ^ Schadt, E. E.; Monks, S. A.; Friend, S. H. (2003). "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. doi:10.1042/bst0310437. PMID 12653656. Archived from the original on 2013-04-14. Retrieved 2013-01-30.
  11. ^ Schadt, E. E.; Sachs, A.; Friend, S. (2005). "Embracing complexity, inching closer to reality". Science's STKE. 2005 (295): 40. doi:10.1126/stke.2952005pe40. PMID 16077086. S2CID 23744520.
  12. ^ Chen, Y.; et al. (2008). "Variations in DNA elucidate molecular networks that cause disease". Nature. 452 (7186): 429–435. Bibcode:2008Natur.452..429C. doi:10.1038/nature06757. PMC 2841398. PMID 18344982.
  13. ^ Emilsson, V.; et al. (2008). "Genetics of gene expression and its effect on disease". Nature. 452 (7186): 423–428. Bibcode:2008Natur.452..423E. doi:10.1038/nature06758. PMID 18344981. S2CID 1219108.
  14. ^ Schadt, E. E. (2009). "Molecular networks as sensors and drivers of common human diseases". Nature. 461 (7261): 218–223. Bibcode:2009Natur.461..218S. doi:10.1038/nature08454. PMID 19741703. S2CID 4323333.
  15. ^ Yang, X.; et al. (2009). "Validation of candidate causal genes for obesity that affect shared metabolic pathways and networks". Nature Genetics. 41 (4): 415–423. doi:10.1038/ng.325. PMC 2837947. PMID 19270708.
  16. ^ Schadt, E. E.; Friend, S. H.; Shaywitz, D. A. (2009). "A network view of disease and compound screening". Nature Reviews Drug Discovery. 8 (4): 286–295. doi:10.1038/nrd2826. PMID 19337271. S2CID 21562023.
  17. ^ "Sage Bionetworks Seattle | Directors". Archived from the original on 2012-01-27. Retrieved 2013-01-30.
  18. ^ Schadt, E. E.; Turner, S.; Kasarskis, A. (2010). "A window into third-generation sequencing". Human Molecular Genetics. 19 (R2): R227–R240. doi:10.1093/hmg/ddq416. PMID 20858600.
  19. ^ Chin, C. S.; et al. (2011). "The origin of the Haitian cholera outbreak strain". The New England Journal of Medicine. 364 (1): 33–42. doi:10.1056/NEJMoa1012928. PMC 3030187. PMID 21142692.
  20. ^ Rasko, D. A.; et al. (2011). "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. doi:10.1056/NEJMoa1106920. PMC 3168948. PMID 21793740.
  21. ^ a b Fang, G.; et al. (2012). "Genome-wide mapping of methylated adenine residues in pathogenic Escherichia coli using single-molecule real-time sequencing". Nature Biotechnology. 30 (12): 1232–1239. doi:10.1038/nbt.2432. PMC 3879109. PMID 23138224.
  22. ^ Schadt, E. E.; et al. (2013). "Modeling kinetic rate variation in third generation DNA sequencing data to detect putative modifications to DNA bases". Genome Research. 23 (1): 129–141. doi:10.1101/gr.136739.111. PMC 3530673. PMID 23093720.
  23. ^ "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. Retrieved 2017-06-17.
  24. ^ "PacBio CSO Eric Schadt to Lead 'Multiscale Institute' at Mount Sinai - Bio-IT World". Archived from the original on 2011-07-30. Retrieved 2013-01-30.
  25. ^ a b "Eric Schadt of Pacific Biosciences Joins Mount Sinai - NYTimes.com". Archived from the original on 2013-02-24. Retrieved 2013-01-30.
  26. ^ Schadt, E. (2012). "Eric Schadt". Nature Biotechnology. 30 (8): 769–770. doi:10.1038/nbt.2331. PMID 22871721.
  27. ^ "Q&A: Mount Sinai's Andrew Kasarskis on Teaching Students how to Analyze their Own Genomes". GenomeWeb.com. 2012-10-24. Retrieved 2017-06-17.
  28. ^ "Genomics annual report fnl by Mount Sinai Health System". Issuu.com. 2014-05-02. Retrieved 2017-06-17.
  29. ^ "NIH funding boosts new Alzheimer's research on prevention, novel drug targets | National Institutes of Health (NIH)". Nih.gov. 2013-09-18. Retrieved 2017-06-17.
  30. ^ "Cell - Integrated Systems Approach Identifies Genetic Nodes and Networks in Late-Onset Alzheimer's Disease". www.cell.com. Archived from the original on 13 July 2013. Retrieved 27 January 2022.
  31. ^ "Gene Studies Could Point to New Alzheimer's Treatments - US News". Archived from the original on 2014-08-19. Retrieved 2014-08-18.
  32. ^ "The Most Innovative Companies of 2014 by Sector". Fast Company. Retrieved 2017-06-17.
  33. ^ Friend, Stephen H. (2014-05-30). "Clues from the resilient | Science". Science. 344 (6187): 970–972. doi:10.1126/science.1255648. PMID 24876479. S2CID 26492504. Retrieved 2017-06-17.
  34. ^ "The Search for Genes That Prevent Disease". The Atlantic. 2014-05-29. Retrieved 2017-06-17.
  35. ^ "The Resilience Project | Join the Search. Be a Hero". Resilienceproject.me. 2016-04-11. Retrieved 2017-06-17.
  36. ^ "Searching For The Hidden Health Heroes Whose DNA Prevents Disease". Fastcoexist.com. 2014-05-29. Retrieved 2017-06-17.
  37. ^ a b "Our Story". Sema4.com. Retrieved 2021-04-12.
  38. ^ "Introducing Sema4: A Spinout Company of the Mount Sinai Health System | Mount Sinai - New York". Mount Sinai Health System. Retrieved 2021-03-16.
  39. ^ "Sema4 Named to the 2020 CB Insights Digital Health 150, a List of the Most Innovative Digital Health Startups". Retrieved 2021-04-20.
  40. ^ "Sema4 opens 70,000-square-foot clinical lab in Stamford". 3 December 2020. Retrieved 2021-04-12.
  41. ^ "Sema4 to Go Public Through Merger With Special Purpose Acquisition Company". GenomeWeb. 10 February 2021. Retrieved 2021-03-16.
  42. ^ "How the iPhone is Helping Doctors Battle Diseases". Bloomberg.com. 11 March 2015.
  43. ^ "Icahn Institute's Eric Schadt on Data Analysis in Medicine - Bloomberg". Businessweek.com. 2014-03-06. Archived from the original on August 15, 2014. Retrieved 2017-06-17.
  44. ^ "The little girl who may hold the secret to aging". Macleans.ca. 2014-07-20. Retrieved 2017-06-17.
  45. ^ "It's Not Just the Genes | HuffPost". Huffingtonpost.com. 24 October 2013. Retrieved 2017-06-17.
  46. ^ "The World's Most Influential Scientific Minds" (PDF). Sciencewatch.com. 2014. Retrieved 2017-06-17.
  47. ^ "Archived copy" (PDF). Archived from the original (PDF) on 2013-01-20. Retrieved 2013-01-30.{{cite web}}: CS1 maint: archived copy as title (link)
  48. ^ "Eric Schadt, Founder & CEO of Sema4, Named 2020 BioCT Entrepreneur of the Year". Retrieved 2021-04-12.
  49. ^ "schadt, ee - search results". PubMed. Retrieved 2021-04-20.
  50. ^ "Eric Schadt - Google Scholar". Retrieved 2021-04-20.
  51. ^ Schadt, E. E.; et al. (2005). "An integrative genomics approach to infer causal associations between gene expression and disease". Nature Genetics. 37 (7): 710–717. doi:10.1038/ng1589. PMC 2841396. PMID 15965475.
  52. ^ + See all authors and affiliations (2005-12-23). "The Runners-Up | Science". Science. 310 (5756): 1880–1885. doi:10.1126/science.310.5756.1880a. PMID 16373539. S2CID 32119689. Retrieved 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. doi:10.1038/ng.2355. PMC 3593099. PMID 22836096.
  54. ^ Peters, L. A.; et al. (2017). "A functional genomics predictive network model identifies regulators of inflammatory bowel disease". Nature Genetics. 49 (10): 1437–1449. doi:10.1038/ng.3947. PMC 5660607. PMID 28892060.
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