Jonathan Rothberg

Rothberg, January 2008

Jonathan Marc Rothberg (born 1963) is an American scientist and entrepreneur.

Early life

Jonathan Marc Rothberg was born in New Haven, Connecticut to Lillian Rothberg and Henry Rothberg, a chemical engineer. Prior to Rothberg's birth, his parents founded Laticrete International, Inc. a family-owned manufacturer of products for the installation of tile and stone. Rothberg's family established the foundation for his scientific career.[1]

Education and scientific career

Rothberg earned a BS in Chemical Engineering with an option in Biomedical Engineering from Carnegie Mellon University in 1985. He went on to Yale University and earned an MS, M.Phil., and Ph.D. in biology. His thesis at Yale focused on decoding a gene called slit responsible for wiring the nervous system. This work resulted in a cover article in the journal Cell in 1988.

While a graduate student at Yale in 1991, he founded CuraGen, one of the first genomics companies. CuraGen focused on how the proteins encoded in a genome function together, and published the first global proteomic maps of a eukaryotic cell and a metazoan organism (featured on the covers of Nature and Science) and developed drugs for the treatment of metastatic skin and breast cancer. However, after never bringing a drug to market, CellDex Therapeutics acquired CuraGen in 2009 and reduced it to only five employees by October.[2]

In 2000 454 Life Sciences was founded as a subsidiary of Curagen; Rothberg was the CEO of Curagen at the time.[3] It was acquired by Roche Diagnostics in 2007 then closed down by Roche in 2013 after other approaches to sequencing rendered the underlying technology noncompetitive.[4]

Rothberg brought to market a machine for single molecule fluorescent sequencing. 454 Life Sciences and the Baylor College of Medicine Genome Center was the first to complete and make public the sequence of an individual human genome (James D. Watson[5][6]). Published in Nature magazine, that genome was made publicly on GenBank and browsable via the efforts of Lincoln Stein's group [7] contributing to personal genomics. Rothberg initiated the Neanderthal Genome Project in collaboration with Svante Pääbo's group.[8]

Rothberg founded RainDance Technologies, which used droplet-based microfluidics.

Rothberg founded Ion Torrent in 2007, who developed ion semiconductor sequencing which is utilized by their PGM DNA sequencer.[9]

Rothberg founded the Rothberg Institute for Childhood Diseases in 2002.[10] He and his wife Bonnie Gold-Rothberg have five children. One of them was affected by the rare genetic disease tuberous sclerosis, and the non-profit institute specialized in treating that disease.[11] The institute ran a distributed computing project called Community TSC until April 2009.[12] The TSC project was based on technology known as the Drug Design and Optimization Lab (D2OL), which the institute sponsored through 2009, to use volunteers' personal computers to model interactions of drug candidates with their target molecules.[13]

Rothberg is a member of the National Academy of Engineering, the Connecticut Academy of Medical Science and Engineering, and is a life of trustees of Carnegie Mellon University.

Positions and honors

Positions

Honors and awards

Professional memberships

2004-2008 Member, Young Presidents’ Organization National Academy of Engineering Connecticut Academy of Medical Science and Engineering Carnegie Mellon University Board of Trustees

Selected Publications

  1. Rothberg, J.M. et al., An integrated semiconductor device enabling non-optical genome sequencing. Nature 475, July 2011. 348-352.
  2. Alexander Mellmann., Dag Harmsen., Craig A. Cummings., Emily B. Zentz, Shana R. Leopold, Alain Rico, Karola Prior, Rafael Szczepanowski, Yongmei Ji, Wenlan Zhang, Stephen F. McLaughlin, John K. Henkhaus, Benjamin Leopold, Martina Bielaszewska, Rita Prager, Pius M. Brzoska, Richard L. Moore, Simone Guenther, Jonathan M. Rothberg, Helge Karch. Prospective genomic characterization of the German enterohemorrhagic Escherichia coli O104:H4 outbreak by rapid next generation sequencing technology. PLOS one, Volume 6, Issue 7, July 2011.
  3. E. Brouzes, M. Medkova, N Savenelli, D. Marran, M. Twardowski, J. B. Hutchinon, J. J. M. Rothberg, D.R. Link, N. Perrimon, M. L. Samuels. Droplet microfluidic technology for single-cell high thoughput screening. PNAS, July 2009, Vol. 106, no. 106
  4. Birgitte B. Simen, Jan Fredrik Simons, Katherine Huppler Hullsiek, Richard M. Novak, Rodger D. MacArthur, John D. Baxter, Chunli Huang, Christine Lubeski, Gregory S. Turenchalk, Michael S. Braverman, Brian Desany, Jonathan M. Rothberg, Michael Egholm, Michael J. Kozal. Low-Abundance Drug-Resistant Viral Variants in Chronically HIV-Infected, Antiretroviral Treatment-Naïve Patients Significantly Impact Treatment Outcomes. The Journal of Infectious Diseases. 2009; 199:693-701.
  5. Richard E Green, Anna-Sapfo Malaspinas, Johannes Krause, Adrian W Briggs, Philip L F Johnson, Caroline Uhler, Matthias Meyer, Jeffrey M Good, Tomislav Maricic, Udo Stenzel, Kay Prüfer, Michael Siebauer, Hernán A Burbano, Michael Ronan, Jonathan M Rothberg, Michael Egholm, Pavao Rudan, Dejana Brajković, Zeljko Kućan, Ivan Gusić, Mårten Wikström, Liisa Laakkonen, Janet Kelso, Montgomery Slatkin, Svante Pääbo. A complete neandertal mitochondrial genome sequence determined by high-throughput sequencing. [Cover Paper] Cell. 2008 Aug 8;134 (3):416-26
  6. David A Wheeler, Maithreyan Srinivasan, Michael Egholm, Yufeng Shen, Lei Chen, Amy McGuire, Wen He, Yi-Ju Chen, Vinod Makhijani, G Thomas Roth, Xavier Gomes, Karrie Tartaro, Faheem Niazi, Cynthia L Turcotte, Gerard P Irzyk, James R Lupski, Craig Chinault, Xing-Zhi Song, Yue Liu, Ye Yuan, Lynne Nazareth, Xiang Qin, Donna M Muzny, Marcel Margulies, George M Weinstock, Richard A Gibbs, Jonathan M Rothberg. The complete genome of an individual by massively parallel DNA sequencing. Nature 2008 Apr 17;452 (7189):872-6
  7. John H. Leamon, Michael S. Braverman and Jonathan M. Rothberg. High-Throughput, Massively Parallel DNA Sequencing Technology for the Era of Personalized Medicine? Gene Therapy and Regulation, 2007, vol. 2, no. 1, 15-31.
  8. John H. Leamon and Jonathan M. Rothberg. Cramming More Sequencing Reactions onto Microreactor Chips. Chemical Reviews, 2007 Aug; 107(8):3367-76.
  9. Green, R.E., Krause, J., Ptak, S.E., Briggs, A.W., Ronan, M., Simons, J.F., Egholm, M., Rothberg, J., Paunovic, M., and Pääbo, S.: Analysis of one million base pairs of Neandertal DNA. [Cover Paper] Nature 444, 330-336.16 November 2006
  10. Robert Pinard, Alex de Winter, Gary J Sarkis, Mark B Gerstein, Karrie R Tartaro, Ramona N Plant, Michael Egholm, Jonathan M Rothberg, and John H Leamon. Assessment of whole genome amplification-induced bias through high-throughput, massively parallel whole genome sequencing. BMC Genomics. 2006; 7: 216. Published online 2006 August 23.
  11. Stiller, M., Green, R.E., Ronan, M., Simons, J.F., Du, L., He, W., Egholm, M., Rothberg, J., Keates, S.G., Ovodov, N.D., Antipina, E.E., Baryshnikov, G.F., Kuzmin, Y.V., Vasilevski, A.A., Wuenschell, G.E., Termini, J., Hofreiter, M., Jaenicke-Després, V., and Pääbo, S.: Patterns of nucleotide misincorporations during enzymatic amplification and direct large-scale sequencing of ancient DNA. PNAS, September 12, 2006, vol. 103, no. 37, 13578-13584.
  12. Thomas RK, Nickerson E, Simons JF, Janne PA, Tengs T, Yuza Y, Garraway LA, Laframboise T, Lee JC, Shah K, O'neill K, Sasaki H, Lindeman N, Wong KK, Borras AM, Gutmann EJ, Dragnev KH, Debiasi R, Chen TH, Glatt KA, Greulich H, Desany B, Lubeski CK, Brockman W, Alvarez P, Hutchison SK, Leamon JH, Ronan MT, Turenchalk GS, Egholm M, Sellers WR, Rothberg JM, Meyerson M. Sensitive mutation detection in heterogeneous cancer specimens by massively parallel picoliter reactor sequencing. Nat Med. 2006 Jul;12(7):852-855.
  13. Leamon JH, Link DR, Egholm M, Rothberg JM. Overview: methods and applications for droplet compartmentalization of biology. Nat Methods. 2006 Jul;3(7):541-3.
  14. Thomas RK, Greulich H, Yuza Y, Lee JC, Tengs T, Feng W, Chen TH, Nickerson E, Simons J, Egholm M, Rothberg JM, Sellers WR, and Meyerson ML. Detection of oncogenic mutations in the EGFR gene in lung adenocarcinoma with differential sensitivity to EGFR tyrosine kinase inhibitors. Cold Spring Harb Symp Quant Biol. 2005; 70: 73-81.
  15. Margulies M, Egholm M, Altman WE, Attiya S, Bader JS, Bemben LA., Berka J, Braverman MS, Chen YJ, Chen Z, Dewell SB, de Winter A, Drake J, Du L, Fierro JM, Forte R, Gomes XV, Godwin BC, He W, Helgesen S, Ho CH, Hutchison SK, Irzyk GP, Jando SC, Alenquer MLI, Jarvie TP, Jirage KB, Kim JB, Knight JR, Lanza JR, Leamon JH, Lee WL, Lefkowitz SM, Lei M, Li J, Lohman KL, Lu H, Makhijani VB, McDade KE, McKenna MP, Myers EW, Nickerson E, Nobile JR, Plant R, Puc BP, Reifler M Ronan MT, Roth GT, Sarkis GJ, Simons JF, Simpson JW, Srinivasan M, Tartaro KR, Tomasz A, Vogt KA, Volkmer GA, Wang SH, Wang Y, Weiner MP, Willoughby DA, Yu P, Begley RF, Rothberg JM. Genome sequencing in microfabricated high-density picolitre reactors. Nature 2005; 441.7089.
  16. Gunther EC, Stone DJ, Rothberg JM, and Gerwien RW. A quantitative genomic expression analysis platform for multiplexed in vitro prediction of drug action. The Pharmacogenomics Journal 5, 2005, 126-134.
  17. Gould Rothberg BE, Pena CEA, Rothberg JM. A systems biology approach to target identification and validation for human chronic disease drug discovery. Division of Chronic Disease Epidemiology, Yale University School of Public Health. Modern Biopharmaceuticals 2005; 1 99-125.
  18. Bader JS, Chaudhuri A. Rothberg JM, and Chant J. Gaining confidence in high-throughput protein interaction networks. Nature Biotechnology 2003; 10.1038.
  19. Leamon JH, Lee WL, Tartaro KR Lanza JR, Sarkis GJ, deWinter AD, Berka J, Weiner M, Rothberg JM, Lohman KL. A massively parallel PicoTitlerPlate based platform for discrete picoliter-scale polymerase chain reactions. Electrophoresis 24(21). November 2003:3769-77, Erratum in Eletrophoresis.25 1176 April 204: 7-8.
  20. Giot L, Bader JS, Brouwer C, Chaudhuri A, Kuang B, Li Y, Hoa YL, Oi CE, Godwin G, Vitols E, Vijayadamodar G, Pochart P, Machineni H, Welsh, M, Kong Y, Zerhusen B, Malcolm R, Varrone Z, Collis A, Minto M, Burgess S, McDaniel L, Stimpson E, Springs F, Williams J, Neurath K, Ioime N, Agee M, Voss E, Furkat K, Renzulli R, Aanensen N, Carrolla S, Bickelhaupt E, Lazovatsky Y, DaSilva A, Zhong J, Stanyon CA, Finley Jr RL, White KP, Braverman M, Jarvie T, Gold S, Leach M, Knight J, Shimkets RA, McKenna MP, Chant J, and Rothberg JM. Protein Interaction Map of Drosophila melanogaster. [Cover paper] Science November 2, 2003; 10.1126.
  21. Bader JS, Deem MW, Hammond RW, Henck SA, Simpson JW, Rothberg JM. A Brownian-ratchet DNA pump with applications to single-nucleotide polymorphism genotyping. Applied Physics A: Materials Science & Processing. 2000; Vol. 75, 275-278.
  22. Tchernev VT, Mansfield TA, Giot L, Kumar AM, Nandabalan K; Li Y, Mishra VS, Detter JC, Rothberg JM, Wallace MR, Southwick FS, Kingsmore SF. The Chediak-Higashi protein interacts with SNARE complex and signal transduction proteins. Molecular Medicine 2002; Vol. 8, 56-64.
  23. LaRochelle WJ, Jeffers M, McDonald WF, Chillakuru RA, N Lokker NA, Sullivan C, Boldog FL, Yang, M, Vernet C, Burgess CE, Fernandes E, Deegler LL, Rittman B, Shimkets J, Shimkets RA, Rothberg JM, and Lichenstein HS. PDGF-D, a new protease-activated growth factor. Nature Cell Biology May 1, 2001; Vol. 3. 517-521.
  24. Herrmann J, Rastelli L, Brugess CE, Fernandes EE, Rothberg BEG, Rothberg JM, and Shimkets RA. Implications of Oncogenomics for Cancer Research and Clinical Oncology. The Cancer Journal. January/February 2001; Volume 7 Number 1.
  25. Rothberg BEG, Sundseth SS, DiPippo VA, Brown PJ, Winegar DA, Gottshalk WK, Shenoy SG, and Rothberg JM. The characterization of PPARα ligand drug action in an in vivo model by comprehensive differential gene expression profiling. [Cover paper] Functional and Integrative Genomics. October 2000.
  26. Uetz P, Giot L, Cagney G, Mansfield TA, Judson RS, Knight JR, Lockshon D, Narayan V, Sriivasan M, Pochart P, Qureshi-Emili A, Li Y, Godwin B, Conver D, Kalbfleisch T, Vijayadamodar G, Yang M, Johnston M, Fields S, and Rothberg JM. A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae. [Cover paper] Nature Feb 10, 2000; Vol. 403, 623-627.
  27. Simpson JW, Ruiz-Martinez MC, Mulhern GT, Berka J, Latimer DR, Ball JA, Rothberg JM, Went GT. A transmission imaging spectrograph and microfabricated channel system for DNA analysis. Electrophoresis 2000; Vol. 21, 135-149.
  28. Hammond RW, Bader JS, Henck SA, Deem MW, McDermott GA, Bustillo JM, Rothberg, JM. Differential transport of DNA by a rectified Brownian motion device. Electrophoresis 2000; Vol. 21, 74-80.
  29. Bader J, Hammond R W, Henck SA, Deem MW, McDermott GA, Bustillo JM, Simpson JW, Mulhern GT, and Rothberg JM. DNA transport by a micromachined Brownian ratchet device. PNAS USA November 9, 1999; Vol. 96 No. 23. 13165-9.
  30. Shimkets R A, Lowe DG, Tsu-Ning Tai J, Sehl P, Jin H, Yang R, Predki P, Rothberg BEG, Murtha MT, Roth ME, Shenoy SG, McKenna MP, Hillan K, Went GT, and Rothberg JM. Gene expression analysis by transcript profiling coupled to a gene database query [GeneCalling]. Nature Biotechnology August 1999; Vol. 17, 798-803.
  31. Rothberg JM, and Artavanis-Tsakonas S. Modularity of the Slit Protein. J. Mol. Biol. 1992; 227, 367-370.
  32. Rothberg JM. Gene Patents. Nature 1992; 356, 738.
  33. Rothberg JM Ph.D. slit: an Extracellular Protein Necessary for the Development of Midline Glia and Axon Pathways of the Central Nervous System contains both EGF and Flank-LRR-Flank Domains. Thesis, Yale University, 1991.
  34. Rothberg JM, Jacobs J R, Goodman CS and Artavanis-Tsakonas S. slit: An Extracellular Protein Necessary for Development of Midline Glia and Commissural Axon Pathways Contains both EGF and LRR Domains. Genes & Development 1990; 4, 2169-2187.
  35. Rothberg JM, Hartley DA, Walther Z, and Artavanis-Tsakonas S. slit: An EGF-Homologous Locus of D. melanogaster Involved in the Development of the Embryonic Central Nervous System. [Cover paper] Cell 1988; 55, 1047-1059.

Issued U.S. Patents

  1. Rothberg J, Wolfgang H, Johnson K, Bustillo J, Methods and apparatus for measuring analytes using large scale FET arrays. USP# 7,948.015
  2. Berka J, Chen YJ, Leamon JH, Lefkowitz S, Lohman KL, Makhijani VB, Rothberg JM, Sarkis GJ, Srinivasan M, Weiner MP. Bead Emulsion Nucleic Acid Amplification. USP# 7,842,457
  3. Rothberg, JM, Bader JS, Dewell SB, McDade K, Simpson JW, Berka, Colangelo CM, Weiner, MP. Apparatus and Method for Sequencing a Nucleic Acid. USP# 7,335,762
  4. Leamon; JH., Lohman; KL., Rothberg; JM. & Weiner MP. Methods of amplifying and sequencing nucleic acids; United States Patent 7,323,305 & European Patent EP1590477
  5. Chen Y, Leamon JH, Lohman KL, Ronan MT, Rothberg JM, Srinivasan M, Weiner MP. Double Ended Sequencing. USP# 7,244,567
  6. Rothberg JM, Bader JS, Dewell SB, McDade K, Simpson JW, Berka J, Colangelo CM. Method of sequencing a nucleic acid. USP# 7,244,559
  7. Rothberg JM, Bader JS, Dewell SB, McDade K, Simpson JW, Berka J, Colangelo CM. Method of sequencing a nucleic acid. USP# 7,211,390.
  8. Rothberg JM, Deem MW, Simpson JW. Detection and confirmation of nucleic acid sequences by use of poisoning oligonucleotides. USP# 6,673,577.
  9. Simpson JW, Rothberg JM, Went, GT, Ruiz-Martinez MC, Mulhern GT. Apparatus and method for the generation, separation, detection, and recognition of biopolymer fragments. USP# 6,485,625.
  10. Rothberg JM, Deem MW, Simpson JW. Method and Apparatus for Identifying, Classifying, or Quantifying DNA Sequences in a Sample without Sequencing. USP # 6,453,245
  11. Rothberg JM, Deem MW, Simpson JW. Method and Apparatus for Identifying, Classifying, or Quantifying DNA Sequences in a Sample without Sequencing. USP # 6,432,361
  12. Rothberg JM, Deem MW, Simpson JW. Method and Apparatus for Identifying, Classifying, or Quantifying DNA Sequences in a Sample without Sequencing. USP # 6,418,382
  13. Nandabalan K, Rothberg JM, Yang M, Knight JR, Kalbfleisch TS. Identification and comparison of protein—protein interactions that occur in populations and identification of inhibitors of these interactors. USP# 6,410,239.
  14. Nandabalan K, Rothberg JM. Identification and comparison of protein-protein interactions that occur in populations and identification of inhibitors of these interactors. USP# 6,395,478.
  15. Rothberg JM, Nallur GN, Hu X. Methods and devices for measuring differential gene expression. USP# 6,355,423.
  16. Deem MW, Rothberg JM, Went GT. Consensus configurational bias Monte Carlo method and system for pharmacophore structure determination. USP# 6,341,256.
  17. Rothberg JM, Bader JS. Method of sequencing a nucleic acid. USP # 6,274,320.
  18. Simpson JW, Rothberg JM, Went GT. Apparatus and method for the generation, separation, detection, and recognition of biopolymer fragments. USP # 6,236,945.
  19. Rothberg JM, Deem MW, Simpson JW. Method and apparatus for identifying, classifying, or quantSimpson JW, Rothberg JM, Went GT. Apparatus and method for the generation, separation, detection, and recognition of biopolymer fragments. USP # 6,218,121.
  20. Bader JS, Rothberg JM, Deem MW, Mulhern GT, Went GT, Simpson JW, Henck S. Separation of charged particles by a spatially and temporally varying electric field. USP # 6,193,866.
  21. Rothberg JM, Deem MW, Simpson JW. Method for identifying a nucleic acid sequence. USP # 6,190,868.
  22. Rothberg JM, Deem MW, Simpson JW. Method and Apparatus for Identifying, Classifying, or Quantifying DNA Sequences in a Sample without Sequencing. USP # 6,141,657.
  23. Nandabalan K, Rothberg JM. Identification and comparison of protein-protein interactions that occur in populations. USP # 6,083,693.
  24. Nandabalan K, Rothberg JM, Yang M, Knight JR, Kalbfleisch TS. Identification and comparison of protein-protein interactions that occur in populations and identification of inhibitors of these interactors. USP # 6,057,101.
  25. Simpson JW, Rothberg JM, Went GT. Apparatus and method for the generation, separation, detection, and recognition of biopolymer fragments. USP # 6,017,434.
  26. Simpson JW, Went GT and Rothberg JM. Apparatus and Method for the Generation, Separation, Detection and Recognition of Biopolymer Fragments. USP # 5,993,634.
  27. Simpson JW, Went GT, and Rothberg JM. Apparatus and Method for the Generation, Separation, Detection and Recognition of Biopolymer Fragments. USP #5,972,693.
  28. Bader J, Rothberg JM, Deem MW, Mulhern GT and Went GT. Nano Niagara Separation of Charged Particles by a Spatially and Temporally varying Electric Field. USP #5,938,904.
  29. Rothberg JM, Went GT, and Simpson JW. Method and Apparatus for Identifying, Classifying, or Quantifying DNA Sequences in a Sample without Sequencing. USP #5,871,697.

References

  1. 1 2 "Jonathan M. Rothberg" (PDF). 2010 Connecticut Medal of Technology bio. Connecticut Academy of Science and Engineering. June 18, 2010. Retrieved November 14, 2016.
  2. ↑ Eric Gerson (October 10, 2009). "A Smaller CuraGen Corp. To Stay Open In Branford". The Hartford Courant. Retrieved November 14, 2016.
  3. ↑ "Curagen Form 10-K for the fiscal year ended December 31, 2000". SEC.
  4. ↑ Hollmer, Mark (October 17, 2013). "Roche to close 454 Life Sciences as it reduces gene sequencing focus". Fierce Biotech.
  5. ↑ Project Jim: Watson’s Personal Genome Goes Public at Bio-IT World.com
  6. ↑ Nicholas Wade (May 31, 2007). "Genome of DNA Pioneer Is Deciphered". The New York Times. Retrieved November 14, 2016.
  7. ↑ James Watson's Personal Genome Sequence
  8. ↑ Analysis of one million base pairs of Neanderthal DNA at Nature.com
  9. ↑ Ion Torrent Official Webpage.
  10. ↑ "Sharing a home, a family and science—two alumni try to make a difference". Yale Medicine Alumni Notes. January 2007. Archived from the original on May 9, 2007. Retrieved November 14, 2016.
  11. ↑ Andrew Pollack (January 4, 2011). "Taking DNA Sequencing to the Masses". The New York Times. Retrieved November 14, 2016.
  12. ↑ "The End of an Era". Rothberg Institute for Childhood Diseases. April 9, 2009. Archived from the original on May 17, 2011. Retrieved November 14, 2016.
  13. ↑ "On April 15, 2009, the D2OL distributed computing project will officially end operations". D2OL web site. Archived from the original on April 19, 2009. Retrieved November 14, 2016.
  14. ↑ Genetics Entrepreneur Jonathan Rothberg Wins CT Medal of Technology, May 18, PRNewswire
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