Michael P. Snyder

Michael Snyder (born 1955) is an American genomicist, systems biologist, and entrepreneur. He is the Stanford B. Ascherman Professor and Chair of Genetics and Director of Genomics and Personalized Medicine at Stanford University School of Medicine.

Michael P Snyder
Born	1955 Pottstown, Pennsylvania
Nationality	American
Occupation	Stanford B. Ascherman Professor Chair of Genetics Department, Stanford University Director of the Center for Genomics and Personalized Medicine
Awards	Pew Scholars Lewis B Cullman named chair (1996)[1] Stanford B. Ascherman named chair (2010) Member of the American Academy of Sciences (elected 2015)

Early life and education

Snyder was born 1955 and grew up outside of Pottstown, Pennsylvania. His father, Kermit Snyder, was an accountant and his mother, Phyllis Snyder, was an elementary school teacher. Snyder attended Owen J Roberts High school in Pottstown, Pennsylvania. He won a Bausch & Lomb science award and attended the University of Rochester, NY where he received a B.A. in Chemistry and Biology. Upon graduation Snyder worked as a research assistant with Karl Drlica at the University of Rochester.

Snyder received a PhD in biology from the California Institute of Technology, where he trained in the laboratory of Dr. Norman Davidson. Recombinant DNA was relatively new at the time and by using this technology to clone a set of gene encoding Drosophila cuticle proteins, Snyder discovered that related genes are often co-associated with one another in the genome ^(1,2). He also discovered one of the first pseudogenes in eukaryotes ⁽²⁾ and made the fundamental discovery that transposons often land in open promoter regions of eukaryotic genes when he discovered a new transposon, HMS Beagle, located in the promoter of an inactivated Drosophila cuticle gene ⁽³⁾ .

Career

Snyder completed his postdoctoral training at Stanford School of Medicine in the laboratory of Dr. Ronald Davis. There he was involved in several projects including establishment of successful cloning of genes using antibodies (lambagt11;) ⁽⁴⁾. The expression libraries he created were used widely by thousands of laboratories worldwide.

Snyder moved to Yale as an Assistant Professor in 1986 in the Department of Biology. His laboratory worked on chromosome segregation and cell polarity for which he discovered a number of important genes involved in these processes ^(5,6). His laboratory proposed the first models by which eucaryotes select sites of cell growth ^(7,8).

He was promoted to Associate Professor with tenure in 1994, and when the Biology Department split in the Molecular, Cellular and Developmental Biology (MCDB) and Ecology and Evolutionary Biology, he became chair of the new MCDB department. During his six years as chair the Department doubled in size and tripled in research funding. He was also the Director for the Center for Genomics and Proteomics at Yale University.

In 2009 Snyder moved to Stanford University to Chair the Genetics Department and to direct the Center for Genomics and Personalized Medicine. Since 2010 the U.S. News & World Report has ranked Stanford University first or tied for first in Genetics, Genomics and Bioinformatics.

Snyder was elected and has served as President of US Human Proteome Organization (2006–2008) and Human Proteome Organization (2017-2018). He has served on numerous scientific advisory committees (e.g. EMBL Scientific Advisory Committee) and is on the Genetics Society Board of Directors (2006–2009). He has organized many scientific meetings.

Snyder has been Principal Investigator of Center of Excellence in the Genome Sciences (CEGS) (2001–2011), NIH Training Grants in Genomics and Proteomics (first at Yale, now at Stanford) (2004–present), and is coDirector of the CIRM Center for Stem Cell Genomics and Director or the Center for Genome of Gene Regulation. He has been a Principal Investigator in the ENCODE project since its inception in 2003.

Research accomplishments

In addition to contributions to the field of cell biology, Snyder’s laboratory has invented a number of novel systems-wide and genomics technologies, and his laboratory has used these to make fundamental biological discoveries.

Systems analyses and Omics Technologies

At a time when most laboratories were studying one or a limited number of genes at a time, Snyder’s laboratory set up the first large scale systems project to study all yeast genes and proteins simultaneously using a transposon tagging strategy to analyze gene expression, protein localization and gene disruption ^(9,10). This was the first large-scale systems analysis of genes and proteins in any organism and launched the field of functional genomics. The libraries and approaches were widely utilized by many laboratories around the world and launched the concept of open sharing and reagents, prior to publication. With Dr. Patrick Brown’s laboratory, the Snyder laboratory invented ChIP-chip ⁽¹¹⁾ (which they later morphed into ChIP-seq ⁽¹²⁾ to carry out the first genome wide mapping of transcription factor binding sites. Initially established for yeast⁽¹¹⁾, they later applied the methods to humans ⁽¹³⁾. This method was foundational for multiple multicenter consortia projects including the Encyclopedia of DNA Elements project (ENCODE; ⁽¹⁴⁾).

Their laboratory constructed the first human chromosome array ⁽¹⁵⁾ and later the first whole genome array ⁽¹⁶⁾ to map TF binding sites and novel transcribed regions of the genome. They later invented RNA-seq to better map transcriptomes, both protein coding and noncoding ^(17,18). Today, this technique is widely employed in the molecular biology field.

With the advent of high throughput DNA sequencing technologies, the Snyder laboratory was the first to sequence an organism using such technology, at a time when most groups thought the technology was too error-prone to be useful. They sequenced Acinetobacter Baummanii, a human pathogen with low error rates ⁽¹⁹⁾. They invented paired end sequencing using new high throughput sequencing technologies ⁽²⁰⁾ and used this to demonstrate that there was ten times as much structural variation (SV) in the human genome a previously realized and that most SV deletions and insertions were due to nonhomologous recombination, a surprising finding at the time, since most SVs were proposed to be due to homologous recombination events.

Beyond the genome, the Snyder lab was also the first to set up protein and proteome microarrays for the large-scale characterization of protein function and antibody reactivity ^(21,22) . They demonstrated many novel biological activities of protein kinases and other yeast proteins and showed they can be useful for autoantibody profiling ⁽²³⁾ .

Biological discoveries

Through their genomics efforts the Snyder laboratory has found that there are many more TF binding sites than were previously appreciated ⁽¹³⁾, with more potential regulatory sequences than RNA coding segments in the human genome (10% versus 3%)⁽²⁴⁾ . In addition to TF binding sites, the Snyder lab discovered that twice as much of the human genome is transcribed into the mature RNA ⁽¹⁶⁾, revealing the widespread occurrence of lincRNAs. These lincRNAs have since been shown to have a diverse array of interesting cellular functions.

Much attention has been paid to understanding the differences individuals and species. The Snyder laboratory was the first to show that transcription factor binding sites vary greatly among people ⁽²⁵⁾ and closely related species, demonstrating that much of the diversity among individuals and closely related species resides at the level of gene regulation ^(27,28), rather than the genes themselves. Much of this variation resides in distal regulatory elements called enhancers.

Omics profiling and data driven medicine

Using the same in-depth omics approaches he applied to yeast, upon his move to Stanford in 2009, Snyder began to apply systems-wide analysis to human health ⁽²⁹⁾. The Snyder laboratory carried out the first deep longitudinal profiling of one person using multi-'omics technologies (genomics, transcriptomics, proteomics, metabolomics, etc.). This deep profiling used genomics for the first time to predict disease risk and follow disease onset at a level not previously achieved ⁽²⁹⁾. This work was recognized as a landmark paper in the journal Cell's 40th anniversary celebration in 2012. This approach of collecting longitudinal deep data on humans is now being applied by many groups worldwide. The Snyder lab has recently demonstrated that self-tracking using wearable biosensor can be used for monitoring health and illness ⁽³⁰⁾ . Together these studies demonstrate the power of using longitudinal tracking and big data to manage human health.

Entrepreneur

Snyder has been a co-founder of a number of Biotechnology companies. These include: Exelixis, Protometrix (purchased by Life Technologies, now part of Thermo Fisher), Affomix (purchased by Illumina), Personalis, SensOmics and is founder of Qbio. He also sits on the board of numerous other biotechnology companies.

Awards

Snyder has received the following awards:

• Pew Scholars (1987)
• Lewis B Cullman named chair (1996)
• Connecticut Medal of Science (2007)
• Stanford B. Ascherman named chair (2010)
• Member of the American Academy of Sciences (elected 2015)
• George W. Beadle Award, Genetics Society of America (2019)

He has been listed in the "Most Cited Scientists since 2014" and has given many distinguished and named lectureships. Since 2009 these include:

• Univ of Pennsylvania, Bernard Cohen Lecture (2009)
• EMBL Dintinguished Lecturer (2011)
• Distinguished Green Lecture Series in Systems Biology at UT Dallas (2012)
• Honorary Lecture at the Genetica Retraite in Rolduc, Maastricht (2013)
• Valdosa College Connell Lectureship (2013)
• Walbash College Special Lectureship (2013)
• General Electric Lectureship McGill Univ. (2014)
• Greenberg Lectureship, Univ. of Michigan (2014)
• Burdette Lecture, Univ. Texas, Austin (2015)
• Murdock Lecture in Stockholm (2015)
• Gerald Aubach Lecture ASBMP (2016)
• Distinguished Lectureship, Cedars-Sinai (2016)
• UC Davis/UC Dublin Kinsella lectureship/Award (2016)
• Wright Lecture in Geneva (2016)
• Gibbs Lecture (2017)

Publications and book

Snyder has authored over 500 published manuscripts.

He has authored a book for a general audience: "Genomics and Personalized Medicine: What Everyone Needs to Know". Oxford University Press. 2016. It describes the utility of genome sequencing, other omics technologies and big data in medicine and prospects for the future.

References

1. Connecticut Medal of Science (2007)

1. Snyder M, Hirsh J, Davidson N. The cuticle genes of Drosophila: a developmentally regulated gene cluster. Cell. 1981;25: 165-177
2. Snyder M, Hunkapiller M, Yuen D, Silvert D, Fristrom J, Davidson N. Cuticle protein genes of Drosophila: structure, organization and evolution of four clustered genes. Cell. 1982;29: 1027-1040.
3. Snyder M, Kimbrell D, Hunkapiller M, Hill R, Fristrom J, Davidson N. A transposable element that splits the promoter region inactivates a Drosophila cuticle protein gene. Proc Natl Acad Sci USA. 1982;79: 7430-7434.
4. Snyder M, Davis RW. Screening gt11 expression libraries with antibody probes. Hybridomas in the Biosciences and Medicine, 1985. Timothy Springer, ed., Plenum Press, N.Y. p. 397-406.
5. Page BD, Snyder M. CIK1: a developmentally regulated spindle pole body-associated protein important for microtubule functions in Saccharomyces cerevisiae. Genes Devel. 1992;6: 1414-1429.
6. Roemer T, Madden K, Chang J, Snyder M. Selection of axial growth sites in yeast requires Axl2p, a novel plasma membrane glycoprotein. Genes Devel. 1996;10: 777-793.
7. Snyder M, Gehrung S, Page BD. Studies concerning the temporal and genetic control of cell polarity in Saccharomyces cerevisiae. J. Cell Biol. 1991;114: 515-532.
8. Flescher EG, Madden K, Snyder M. Components required for cytokinesis are important for bud site selection in yeast. J. Cell Biol. 1993;122: 373-386.
9. Burns N, Grimwade B, Ross-Macdonald PB, Choi EY, Finberg K, Roeder GS and Snyder M. Large-scale analysis of gene expression, protein localization, and gene disruption in Saccharomyces cerevisiae. Genes Dev. 1994;8:1087-105.
10. Ross-Macdonald P, Coelho PSR, Roemer T, Agarwal S, Kumar A, Jansen R, Cheung K-H, Sheehan A, Symoniatis D, Umansky L, Heitman M, Nelson FK, Iwasaki H, Hager K, Gerstein M, Miller P, Roeder GS, Snyder M. Large-scale analysis of the yeast genome by transposon tagging and gene disruption. Nature. 1999; 402: 413-418.
11. Iyer VR, Horak CE, Scafe CS, Botstein D, Snyder M and Brown PO. Genomic binding sites of the yeast cell-cycle transcription factors SBF and MBF. Nature. 2001;409:533-8.
12. Robertson G, Hirst M, Bainbridge M, Bilenky M, Zhao Y, Zeng T, Euskirchen G, Bernier B, Varhol R, Delaney A, Thiessen N, …, Snyder M and Jones S. Genome-wide profiles of STAT1 DNA association using chromatin immunoprecipitation and massively parallel sequencing. Nat Methods. 2007;4:651-7.
13. Horak CE, Mahajan MC, Luscombe NM, Gerstein M, Weissman SM, Snyder M. GATA-1 binding sites mapped in the beta-globin locus by using mammalian ChIP-chip analysis. Proc Natl Acad Sci USA. 2002;99: 2924-
14. The ENCODE Project Consortium. “An Integrated Encyclopedia of DNA Elements in the Human Genome.” Nature. 2012. 489(7414): 57-74.
15. Rinn JL, Euskirchen G, Bertone P, Martone R, Luscombe NM, Hartman S, Harrison PM, Nelson FK, Miller P, Gerstein M, Weissman S and Snyder M. The transcriptional activity of human Chromosome 22. Genes Dev. 2003;17:529-40.
16. Bertone P, Stolc V, Royce TE, Rozowsky JS, Urban AE, Zhu X, Rinn JL, Tongprasit W, Samanta M, Weissman S, Gerstein M, Snyder M. Global identification of human transcribed sequences with genome tiling arrays. Science. 2004;306: 2242-6.
17. Nagalakshmi U, Wang Z, Waern K, Shou C, Raha D, Gerstein M and Snyder M. The transcriptional landscape of the yeast genome defined by RNA sequencing. Science. 2008;320:1344-9.
18. Wang Z, Gerstein M, Snyder M. RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet. 2009 Jan;10(1):57-63. PMID 19015660.
19. Smith MG, Gianoulis TA, Pukatzki S, Mekalanos J, Ornston LN, Gerstein M, Snyder M. New insights into Acinetobacter baumannii pathogenesis revealed by high-density pyrosequencing and transposon mutagenesis. Genes Dev. 2007;21: 601-14.
20. Korbel, JO,* Urban AE,* Affourtit J,* Godwin B, Grubert F, ... Snyder M. Paired-end mapping reveals extensive structural variation in the human genome. Science. 2007;318: 420-6.
21. Zhu H, Bilgin M, Bangham R, Hall D, Casamayor A, Bertone P, Lan N, Jansen R, Bidlingmaier S, Houfek T, Mitchell T, Miller P, Dean DA, Gerstein M, Snyder M. Global analysis of protein activities using proteome chips. Science. 2001;293: 2101-2105.
22. Zhu H, Klemic JF, Chang S, Bertone P, Klemic KG, Smith D, Gerstein M, Reed MA, Snyder M. Analysis of yeast protein kinases using protein chips. Nat Genet. 2000;26: 283-289.
23. Hudson ME, Pozdnyakova I, Haines K, Mor G, Snyder M. Identification of differentially expressed proteins in ovarian cancer using high-density protein microarrays. Proc Natl Acad Sci USA. 2007;104: 17494-9.
24. Kellis M, Wold B, Snyder MP, Bernstein BE, Kundaje A, Marinov GK, Ward LD, Birney E, Crawford GE, Dekker J, Dunham I, Elnitski LL, Farnham PJ, Feingold EA, Gerstein M, Giddings MC, Gilbert DM, Gingeras TR, Green ED, Guigo R, Hubbard T, Kent J, Lieb JD, Myers RM, Pazin MJ, Ren B, Stamatoyannopoulos J, Weng Z, White KP, Hardison RC. Reply to Brunet and Doolittle: Both selected effect and causal role elements can influence human biology and disease. Proc Natl Acad Sci U S A. 2014 Aug 19;111(33):E3366. No abstract available. PMID 25275169
25. Kasowski M, Grubert F, Heffelfinger C, Hariharan M, Asabere A, Waszak SM, Habegger L, Rozowsky J, Shi M, Urban AE, … Weissman SM, Gerstein MB, Korbel JO, Snyder M. Variation in transcription factor binding among humans. Science. 2010. 328(5975): 232-5. Epub 2010. PMID 20299548.
26. Borneman AR, Gianoulis TA, Zhang ZD, Yu H, Rozowsky J, Seringhaus MR, Wang LY, Gerstein M, Snyder M. Divergence of transcription factor binding sites across related yeast species. Science. 2007;317: 815-19.
27. Grubert F, Zaugg JB, Kasowski M, Ursu O, Spacek DV, Martin AR, Greenside P, Srivas R, Phanstiel DH, Pekowska A, Heidari N, Euskirchen G, Huber W, Pritchard JK, Bustamante CD, Steinmetz LM, Kundaje A, Snyder M. Genetic Control of Chromatin States in Humans Involves Local and Distal Chromosomal Interactions. Cell. 2015 Aug 27;162(5):1051-65. doi: 10.1016/j.cell.2015.07.048. Epub 2015 Aug 20. PMID 26300125
28. Kasowski M, Kyriazopoulou-Panagiotopoulou S, Grubert F, Zaugg JB, Kundaje A, Liu Y, Boyle AP, Zhang QC, Zakharia F, Spacek DV, Li J, Xie D, Olarerin-George A, Steinmetz LM, Hogenesch JB, Kellis M, Batzoglou S, Snyder M. Extensive variation in chromatin states across humans. Science. 2013 Nov 8;342(6159):750-2. PMID 24136358
29. Chen R, Mias GI, Li-Pook-Than J, Jiang L, … Snyder M. Personal omics profiling reveals dynamic molecular and medical phenotypes. Cell. 2012;148:1293-307.
30. Li X, Dunn J, Salins D, Zhou G, Zhou W, Schüssler-Fiorenza Rose SM, Perelman D, Colbert E, Runge R, Rego S, Sonecha R, Datta S, McLaughlin T, Snyder M. Digital Health: Tracking Physiomes and Activity Using Wearable Biosensors Reveals Useful Health-Related Information. PLoS Biol. 2017 Jan 12;15(1):e2001402. doi: 10.1371/journal.pbio.2001402. PMID 28081144