Robert B. Darnell

Robert Bernard Darnell (born October 29, 1957) is an American neurooncologist and neuroscientist, founding director and former CEO of the New York Genome Center, the Robert and Harriet Heilbrunn Professor of Cancer Biology at The Rockefeller University,[5] and an Investigator of the Howard Hughes Medical Institute. His research into rare autoimmune brain diseases led to the invention of the HITS-CLIP method to study RNA regulation, and he is developing ways to explore the regulatory portions—known as the "dark matter"—of the human genome.[6]

Robert B. Darnell
Darnell lecturing in 2010
Born
Robert Bernard Darnell

(1957-10-29) October 29, 1957
Washington, D.C.
NationalityAmerican
CitizenshipUnited States
Alma materColumbia College, Columbia University, Washington University School of Medicine, Mt. Sinai School of Medicine, Weill Cornell Medical College, Memorial Sloan-Kettering Cancer Center
Known forTranslational Basic and Medical Research
RNA regulation in the brain
(2003) Publication of RNA CLIP method[1]
Awards2010 National Academy of Medicine
2012 NIH Director's Transformative Award[2]
2014 National Academy of Sciences
2015 Columbia University Medical Center & New York-Presbyterian Health Sciences Advisory Council Distinguished Service Award as Director of NY Genome Center[3]
2017 NINDS Research Program Award (R35)[4]
Scientific career
FieldsNeurooncology
Neuroscience
Immunology
InstitutionsRockefeller University 1992-present
Howard Hughes Medical Institute 2002-present
Doctoral advisorRobert G. Roeder

At The Rockefeller University Darnell is head of the Laboratory of Molecular Neuro-Oncology,[5] and Senior Physician at the Rockefeller University Hospital,[7] has been an HHMI Investigator since 1992,[8] and an Adjunct Attending Neuro-Oncologist at the Memorial Sloan-Kettering Cancer Center. He was named to the New York Genome Center position on November 28, 2012 a position he held through 2016.[9] His publications can be found via Google Scholar and his ORCID ID 0000-0002-5134-8088.

Career

Darnell's early research was concentrated on paraneoplastic syndromes (PNDs, the paraneoplastic neurologic disorders), disorders touching on various clinical and basic aspects of biology including cancer immunology and neuroimmunology. He was the first to definitively demonstrate that naturally occurring tumor immunity in humans was caused by antigen-specific cytotoxic (CD8+) T cells, helping to generate the foundation for the field of immuno-oncology.[10] His lab was the first to use PND patient antisera to screen expression cDNA libraries to identify the genes encoding the PND antigens.[11][12] This opened the door to the cloning of the Nova,[13] cdr2 and Elavl (Hu) antigens, and led Darnell to hypothesize, based on the intracellular nature of the antigens, that tumor immunity was mediated by CD8+ T cells.[14] His laboratory went on to prove this hypothesis, demonstrating cdr2-specific CD8+ T cells were present in the peripheral blood[10] and cerebrospinal fluid[15] of patients with paraneoplastic cerebellar degeneration associated with tumor immunity to breast or ovarian cancers.

The discovery of that the Nova PND antigen (associated with paraneoplastic opsoclonus-opsoclonus) was the first of a class of neuron-specific RNA-binding proteins led his laboratory to question the nature of RNA regulation in the brain and why it might be co-opted in cancer cells. His laboratory developed the HITS-CLIP technique that is used to map the sites of regulatory interactions between RNA-binding proteins and their target RNA sequences, originally using it to study the Nova proteins[1] and subsequently a large number of other RNA binding proteins that are implicated in brain disease, including FMRP[16] (associated with intellectual disability and autism), RbFox[17] (associated with autism), Mbnl[18] (associated with myotonic dystrophy), Elavl[19] (the Hu PND antigen) and cancer (including RBM47[20] and Argonaute-miRNA interactions,[21] both implicated in breast cancer).

In 2012, Darnell became the founding director and CEO of the New York Genome Center,[22][23] a not-for-profit multi-institutional academic collaborative founded to harness big data, molecular genetics to improve clinical care in an ethical and equitable manner. The center opened in September 2013[24] with support and participation from James Watson, Harold Varmus, New York Mayor Michael Bloomberg, Marc Tessier-Lavigne and many others,[25] growing within 2 years to bring a world-class genomic center to New York.[26] In 2016 NYGC was one of four Genome Centers in the United States to be awarded a large grant from the NIH to use genomic sequencing to study common diseases.[27] After securing a $100M philanthropic grant for NYGC[28] and a seven-year Research Program Award from NINDS,[4] Darnell returned to pursue his work on genomic medicine and neuroscience at the Rockefeller University and HHMI in 2017.

Darnell received his undergraduate degrees in biology and chemistry in 1979 from Columbia University, and his MD/PhD in Molecular Biology in 1985 from Washington University in St. Louis. He was trained in Internal Medicine at Mount Sinai School of Medicine, and in Neurology at Weill Cornell Medical Center, where he was chief resident in 1990 with Fred Plum. He has worked and published extensively with Jerome B. Posner, one of the founders of the study of PNDs, co-authoring a definitive text on the subject.[29] In 2010 he was elected to the Institute of Medicine of the National Academy of Sciences, and a Fellow of the AAAS (the American Association for the Advancement of Science), in 2014 he was elected to the National Academy of Sciences, and in 2019 he was named a Fellow of the American Academy of Arts and Sciences.[30]

Personal life

Darnell comes from a family of scientists; he is the son of American scientist James E. Darnell, another pioneer in RNA research, the father of Alicia Darnell, a postdoctoral fellow at MIT and second-place winner in the 2007 Siemens Competition in Math, Science & Technology,[31][32] as well as the father of Andrew J. Darnell, MBA, who completed a master's in Bioethics and Science Policy at Duke and graduated from Duke Law School in 2019.

Darnell is a passionate amateur cellist; he studied with Gilda Barston, herself a student of Leonard Rose,[33] and Ardith Alton at Juilliard.[34] In 2000, after his mother died of breast cancer, Darnell founded the Chamber Orchestra of Science and Music at Rockefeller University in her honor, saying in an interview with the Burroughs Wellcome Fund Clinical Scientist Award for Translational Research: "I love to breathe in music and art...seeing the intensity others put into life is a source of inspiration".[35]

Darnell is also a triathlete, and has completed the New York City Triathlon every year since 2012[36] except 2019 when the event was cancelled, and Darnell completed the Atlantic City Ironman.[37]

Awards

References (Orcid ID https://orcid.org/0000-0002-5134-8088)
  1. Ule, J.; Jensen, K. B.; Ruggiu, M.; Mele, A.; Ule, A.; Darnell, R. B. (2003). "CLIP Identifies Nova-Regulated RNA Networks in the Brain". Science. 302 (5648): 1212–1215. Bibcode:2003Sci...302.1212U. doi:10.1126/science.1090095. PMID 14615540. S2CID 23420615.
  2. "NIH Director's Transformative Research Award Program - 2012 Award Recipients - NIH Common Fund". commonfund.nih.gov. Retrieved 21 January 2019.
  3. https://www.nygenome.org/wp-content/uploads/2015/10/HSAC-Distinguished-Service-Award-Press-Release.pdf
  4. "NINDS Research Program Award (R35) Recipients FY 2017 - National Institute of Neurological Disorders and Stroke". www.ninds.nih.gov. Retrieved 21 January 2019.
  5. "Robert B. Darnell". rockefeller.edu. Retrieved 21 January 2019.
  6. Kolata, Gina (5 September 2012). "Far From ‘Junk,’ DNA Dark Matter Proves Crucial to Health". Retrieved 21 January 2019 – via NYTimes.com.
  7. "The Rockefeller University Hospital". rockefeller.edu. Retrieved 21 January 2019.
  8. "Robert B. Darnell". HHMI.org. Retrieved 21 January 2019.
  9. "Bio-IT World". www.bio-itworld.com. Retrieved 21 January 2019.
  10. Albert, ML; Darnell, JC; Bender, A; Francisco, LM; Bhardwaj, N; Darnell, RB (1998). "Tumor-specific killer cells in paraneoplastic cerebellar degeneration". Nat Med. 4 (11): 1321–4. doi:10.1038/3315. PMID 9809559. S2CID 10415863.
  11. Darnell, RB; Furneaux, HM; Posner, JB (May 1991). "Antiserum from a patient with cerebellar degeneration identifies a novel protein in Purkinje cells, cortical neurons, and neuroectodermal tumors". J. Neurosci. 11 (5): 1224–30. doi:10.1523/JNEUROSCI.11-05-01224.1991. PMC 6575333. PMID 1851215.
  12. Newman, LS; McKeever, MO; Okano, HJ; Darnell, RB (September 1995). "Beta-NAP, a cerebellar degeneration antigen, is a neuron-specific vesicle coat protein". Cell. 82 (5): 773–83. doi:10.1016/0092-8674(95)90474-3. PMID 7671305. S2CID 8094530.
  13. Buckanovich, RJ; Posner, JB; Darnell, RB (October 1993). "Nova, the paraneoplastic Ri antigen, is homologous to an RNA-binding protein and is specifically expressed in the developing motor system". Neuron. 11 (4): 657–72. doi:10.1016/0896-6273(93)90077-5. PMID 8398153. S2CID 22554933.
  14. Darnell, RB (May 1996). "Onconeural antigens and the paraneoplastic neurologic disorders: at the intersection of cancer, immunity, and the brain". Proc. Natl. Acad. Sci. U.S.A. 93 (10): 4529–36. Bibcode:1996PNAS...93.4529D. doi:10.1073/pnas.93.10.4529. PMC 39311. PMID 8643438.
  15. Albert, ML; Austin, LM; Darnell, RB (January 2000). "Detection and treatment of activated T cells in the cerebrospinal fluid of patients with paraneoplastic cerebellar degeneration". Ann. Neurol. 47 (1): 9–17. doi:10.1002/1531-8249(200001)47:1<9::aid-ana5>3.0.co;2-i. PMID 10632096.
  16. Darnell, JC; Van Driesche, SJ; Zhang, C; et al. (July 2011). "FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism". Cell. 146 (2): 247–61. doi:10.1016/j.cell.2011.06.013. PMC 3232425. PMID 21784246.
  17. Weyn-Vanhentenryck, SM; Mele, A; Yan, Q; Sun, S; Farny, N; Zhang, Z; Xue, C; Herre, M; Silver, PA; Zhang, MQ; Krainer, AR; Darnell, RB; Zhang, C (2014). "HITS-CLIP and integrative modeling define the Rbfox splicing-regulatory network linked to brain development and autism". Cell Rep. 6 (6): 1139–52. doi:10.1016/j.celrep.2014.02.005. PMC 3992522. PMID 24613350.
  18. Charizanis, K; Lee, KY; Batra, R; et al. (August 2012). "Muscleblind-like 2-mediated alternative splicing in the developing brain and dysregulation in myotonic dystrophy". Neuron. 75 (3): 437–50. doi:10.1016/j.neuron.2012.05.029. PMC 3418517. PMID 22884328.
  19. Ince-Dunn, G; Okano, HJ; Jensen, KB; et al. (September 2012). "Neuronal Elav-like (Hu) proteins regulate RNA splicing and abundance to control glutamate levels and neuronal excitability". Neuron. 75 (6): 1067–80. doi:10.1016/j.neuron.2012.07.009. PMC 3517991. PMID 22998874.
  20. Vanharanta, S; Marney, CB; Shu, W; Valiente, M; Zou, Y; Mele, A; Darnell, RB; Massagué, J (2014). "Loss of the multifunctional RNA-binding protein RBM47 as a source of selectable metastatic traits in breast cancer". eLife. 3. doi:10.7554/eLife.02734. PMC 4073284. PMID 24898756.
  21. Chi, SW; Zang, JB; Mele, A; Darnell, RB (July 2009). "Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps". Nature. 460 (7254): 479–86. Bibcode:2009Natur.460..479C. doi:10.1038/nature08170. PMC 2733940. PMID 19536157.
  22. "Darnell to Lead NY Genome Center". www.bio-itworld.com. Retrieved 2019-01-14.
  23. "Robert Darnell named president of New York Genome Center". News. Retrieved 2019-01-14.
  24. Says, Inara (2013-09-19). "Darnell to lead NY Genome Center; Tom Maniatis' Dream Becomes a Big Apple Reality". Xconomy. Retrieved 2019-01-14.
  25. New York Genome Center. "NYGC Opening". Retrieved 21 January 2019 – via YouTube.
  26. "NY Genome Center hits growth spurt". Crain's New York Business. 2014-02-20. Retrieved 2019-01-14.
  27. Center, New York Genome. "The New York Genome Center Awarded $40 Million from the NIH to Use Genomic Sequencing to Explore Common Disease". www.prnewswire.com. Retrieved 2019-01-14.
  28. "$100 Million Gift for the New York Genome Center James H. Simons, PhD, and Russell L. Carson MakeTransformational Joint Gift". New York Genome. Retrieved 2019-01-14.
  29. Darnell, Robert B.; Darnell, Robert; Posner, Jerome B. (22 August 2011). Paraneoplastic Syndromes (Contemporary Neurology Series): 9780199772735: Medicine & Health Science Books @ Amazon.com. ISBN 978-0199772735.
  30. "New 2019 Academy Members Announced". American Academy of Arts & Sciences. Retrieved 2019-06-20.
  31. Millner-Fairbanks, Amanda (4 December 2007). "Girls Make History by Sweeping Top Honors at a Science Contest". Retrieved 21 January 2019 – via NYTimes.com.
  32. Following in family’s footsteps, Alicia Darnell wins national science prize
  33. Kates, Joan Giangrasse. "Gilda Barston, cellist and teacher, dies at 71". chicagotribune.com. Retrieved 2019-01-14.
  34. "Ardyth Alton-Juilliard Pre-College Faculty".
  35. "Interview with Dr. Darnell, recipient of BWF Clinical Scientist Award for Translational Research" (PDF). www.bwfund.org. Retrieved 2019-01-14.
  36. "Results, Photos & TV". nyctri.com. Retrieved 21 January 2019.
  37. "IRONMAN 70.3 Atlantic City - 70.3 Triathlon - Official Race Results at Online Race Results". OnlineRaceResults.com. Retrieved 2020-01-17.
  38. Derek Denny-Brown Young Neurological Scholar Award
  39. "Grant Recipients - Burroughs Wellcome Fund". www.bwfund.org. Retrieved 21 January 2019.
  40. "AAAS Members Elected as Fellows". AAAS - The World's Largest General Scientific Society. 2011-01-11. Retrieved 2018-04-20.
  41. "IOM Elects 65 New Members, Five Foreign Associates : Health and Medicine Division". www.nationalacademies.org. Retrieved 2018-04-20.
  42. "NIH Director's Transformative Research Award Program - 2012 Award Recipients - NIH Common Fund". commonfund.nih.gov. Retrieved 21 January 2019.
  43. National Academy of Sciences Announces 84 New Members, April 29, 2014 Archived August 18, 2015, at the Wayback Machine
  44. "Darnell receives Columbia/NY Presbyterian Award as Leader of NY Genome Center" (PDF). www.nygenome.org. Retrieved 2019-01-14.
  45. "NINDS Research Program Award (R35) Recipients FY 2017 | National Institute of Neurological Disorders and Stroke". www.ninds.nih.gov. Retrieved 2019-01-14.
  46. https://www.amacad.org/news/2019-members-announcement
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