Robert B. Darnell

Robert B. Darnell
Darnell lecturing in 2010
Born Robert Bernard Darnell
(1957-10-29) October 29, 1957
Washington, D.C.
Nationality American
Alma mater Columbia College, Columbia University, Washington University School of Medicine, Mt. Sinai School of Medicine, Weill Cornell Medical College, Memorial Sloan-Kettering Cancer Center
Spouse(s) Jennifer Eve Cordes (m. 1987; 4 children)
Awards National Academy of Science in 2014
Institute of Medicine in 2010
Scientific career
Fields Neurooncology
Neuroscience
Immunology
Doctoral advisor Robert G. Roeder

Robert Darnell is an American neurooncologist and neuroscientist, a founding director and former CEO of the New York Genome Center, the Robert and Harriet Heilbrunn Professor of Cancer Biology at The Rockefeller University,[1] 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.[2]

At The Rockefeller University Darnell is Head of the Laboratory of Molecular Neuro-Oncology,[3] and Senior Physician at the Rockefeller University Hospital,[4] has been an HHMI Investigator since 1992,[5] 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 until 2016.[6]

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, 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.[7] His lab was the first to use PND patient antisera to screen expression cDNA libraries to identify the genes encoding the PND antigens.[8][9] This opened the door to the cloning of the Nova,[10] cdr2 and Elavl (Hu) antigens, and led Darnell to hypothesize, based on the intracellular nature of the antigens, that tumor immunity was mediated not by antibodies but by T cells.[11] His laboratory went on to prove this hypothesis, demonstrating cdr2-specific CD*+ T cells were present in the peripheral blood[12] and cerebrospinal fluid[13] 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[14] and subsequently a large number of other RNA binding proteins that are implicated in brain disease, including FMRP[15] (associated with intellectual disability and autism), RbFox[16] (associated with autism), Mbnl[17] (associated with myotonic dystrophy), Elavl[18] (the Hu PND antigen) and cancer (including RBM47[19] and Argonaute-miRNA interactions,[20] both implicated in breast cancer).

In 2012, Dr. Darnell became the Founding Director and CEO of the New York Genome Center,[21][22] 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[23] with support and participation from James Watson, Harold Varmus, New York Mayor Michael Bloomberg, Marc Tessier-Lavigne and many others.[24] 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.[25]

Dr. 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 Dr. 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.[26] 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), and in 2014 was elected to the National Academy of Sciences.

Personal life

Dr. 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, second-place winner in the 2007 Siemens Competition in Math, Science & Technology,[27] as well as the father to Andrew J. Darnell, MBA, who completed a Masters in Bioethics and Science Policy at Duke and is now a student at Duke Law School, Paul M. Darnell, undergraduate philosophy student at the University of Maryland, College Park, and is married to Jennifer Darnell, a leading authority on the Fragile X syndrome.[28]

Dr. Darnell is a passionate amateur cellist; he studied with Gilda Barston, herself a student of Leonard Rose,[29] until she said she had taught him all she knew, and then studied with Ardith Alton at Juilliard.[30] 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."[31]

Dr. Darnell is also a Triathlete, and has completed the New York City Triathlon every year since 2012.[32]

Awards

References

  1. ↑ The Darnell Laboratory at Rockefeller University
  2. ↑ Bits of Mystery DNA, Far From 'Junk,' Play Crucial Role, NY Times, 2012
  3. ↑ The Darnell Laboratory at Rockefeller University
  4. ↑ The Rockefeller University Hospital
  5. ↑ Robert B. Darnell, Investigator at HHMI
  6. ↑ Physician Scientist Robert Darnell Named President and Scientific Director of New York Genome Center
  7. ↑ Albert, ML; Darnell, JC; Bender, A; Francisco, LM; Bhardwaj, N; Darnell, RB (1998). "Tumor-specific killer cells in paraneoplastic cerebellar degeneration". Nat Med. 4: 1321–4. doi:10.1038/3315. PMID 9809559.
  8. ↑ 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: 1224–30. PMID 1851215.
  9. ↑ 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: 773–83. doi:10.1016/0092-8674(95)90474-3. PMID 7671305.
  10. ↑ 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: 657–72. doi:10.1016/0896-6273(93)90077-5. PMID 8398153.
  11. ↑ 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: 4529–36. doi:10.1073/pnas.93.10.4529. PMC 39311. PMID 8643438.
  12. ↑ Albert, ML; Darnell, JC; Bender, A; Francisco, LM; Bhardwaj, N; Darnell, RB (1998). "Tumor-specific killer cells in paraneoplastic cerebellar degeneration". Nat Med. 4: 1321–4. doi:10.1038/3315. PMID 9809559.
  13. ↑ 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: 9–17. doi:10.1002/1531-8249(200001)47:1<9::aid-ana5>3.0.co;2-i. PMID 10632096.
  14. ↑ Ule, J; Jensen, KB; Ruggiu, M; Mele, A; Ule, A; Darnell, RB (2003). "CLIP identifies Nova-regulated RNA networks in the brain". Science. 302: 1212–5. doi:10.1126/science.1090095. PMID 14615540.
  15. ↑ 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: 247–61. doi:10.1016/j.cell.2011.06.013. PMC 3232425. PMID 21784246.
  16. ↑ 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: 1139–52. doi:10.1016/j.celrep.2014.02.005. PMC 3992522. PMID 24613350.
  17. ↑ 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: 437–50. doi:10.1016/j.neuron.2012.05.029. PMC 3418517. PMID 22884328.
  18. ↑ 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: 1067–80. doi:10.1016/j.neuron.2012.07.009. PMC 3517991. PMID 22998874.
  19. ↑ 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.
  20. ↑ Chi, SW; Zang, JB; Mele, A; Darnell, RB (July 2009). "Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps". Nature. 460: 479–86. doi:10.1038/nature08170. PMC 2733940. PMID 19536157.
  21. ↑
  22. ↑
  23. ↑
  24. ↑
  25. ↑
  26. ↑ Darnell RB and Posner JB. Paraneoplastic Syndromes
  27. ↑ Girls Make History by Sweeping Top Honors at a Science Contest, NY Times, 2007
  28. ↑ Jennifer Darnell, Rockefeller University Research Associate Professor
  29. ↑
  30. ↑
  31. ↑
  32. ↑
  33. ↑ Derek Denny-Brown Young Neurological Scholar Award
  34. ↑ Clinical Scientist Awards in Translational Research
  35. ↑ "AAAS Members Elected as Fellows". AAAS - The World's Largest General Scientific Society. 2011-01-11. Retrieved 2018-04-20.
  36. ↑ "IOM Elects 65 New Members, Five Foreign Associates : Health and Medicine Division". www.nationalacademies.org. Retrieved 2018-04-20.
  37. ↑ 2012 Transformative R01 Award Recipients
  38. ↑ National Academy of Sciences Announces 84 New Members, April 29, 2014 Archived August 18, 2015, at the Wayback Machine.
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