Robert B. Darnell

Last updated
Robert B. Darnell
Professor Robert Darnell.jpg
Darnell lecturing in 2010
Born
Robert Bernard Darnell

(1957-10-29) October 29, 1957 (age 65)
Washington, D.C.
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
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
Fields Neurooncology
Neuroscience
Immunology
InstitutionsRockefeller University 1992-present
Howard Hughes Medical Institute 2002-present
Doctoral advisor Robert G. Roeder

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]

Contents

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

Related Research Articles

<span class="mw-page-title-main">David Baltimore</span> American biologist (born 1938)

David Baltimore is an American biologist, university administrator, and 1975 Nobel laureate in Physiology or Medicine. He is a professor of biology at the California Institute of Technology (Caltech), where he served as president from 1997 to 2006. He founded the Whitehead Institute and directed it from 1982 to 1990. In 2008, he served as president of the American Association for the Advancement of Science in 2008.

<span class="mw-page-title-main">Oncovirus</span> Viruses that can cause cancer

An oncovirus or oncogenic virus is a virus that can cause cancer. This term originated from studies of acutely transforming retroviruses in the 1950–60s, when the term "oncornaviruses" was used to denote their RNA virus origin. With the letters "RNA" removed, it now refers to any virus with a DNA or RNA genome causing cancer and is synonymous with "tumor virus" or "cancer virus". The vast majority of human and animal viruses do not cause cancer, probably because of longstanding co-evolution between the virus and its host. Oncoviruses have been important not only in epidemiology, but also in investigations of cell cycle control mechanisms such as the retinoblastoma protein.

<span class="mw-page-title-main">Spinocerebellar ataxia</span> Medical condition

Spinocerebellar ataxia (SCA) is a progressive, degenerative, genetic disease with multiple types, each of which could be considered a neurological condition in its own right. An estimated 150,000 people in the United States have a diagnosis of spinocerebellar ataxia at any given time. SCA is hereditary, progressive, degenerative, and often fatal. There is no known effective treatment or cure. SCA can affect anyone of any age. The disease is caused by either a recessive or dominant gene. In many cases people are not aware that they carry a relevant gene until they have children who begin to show signs of having the disorder.

<span class="mw-page-title-main">Stiff-person syndrome</span> Human medical condition

Stiff-person syndrome (SPS), also known as stiff-man syndrome, is a rare neurologic disorder of unclear cause characterized by progressive muscular rigidity and stiffness. The stiffness primarily affects the truncal muscles and is superimposed by spasms, resulting in postural deformities. Chronic pain, impaired mobility, and lumbar hyperlordosis are common symptoms.

Paraneoplastic cerebellar degeneration (PCD) is a paraneoplastic syndrome associated with a broad variety of tumors including lung cancer, ovarian cancer, breast cancer, Hodgkin’s lymphoma and others. PCD is a rare condition that occurs in less than 1% of cancer patients.

A paraneoplastic syndrome is a syndrome that is the consequence of a tumor in the body. It is specifically due to the production of chemical signaling molecules by tumor cells or by an immune response against the tumor. Unlike a mass effect, it is not due to the local presence of cancer cells.

<span class="mw-page-title-main">HuD (protein)</span> Protein found in humans

HuD otherwise known as ELAV-like protein 4 is a protein that in humans is encoded by the ELAVL4 gene.

<span class="mw-page-title-main">CDR2 (gene)</span> Protein-coding gene in the species Homo sapiens

Cerebellar degeneration-related protein 2 is a protein that in humans is encoded by the CDR2 gene.

<span class="mw-page-title-main">NOVA1</span> Protein-coding gene in the species Homo sapiens

RNA-binding protein Nova-1 is a protein that in humans is encoded by the NOVA1 gene.

<span class="mw-page-title-main">AP3B2</span> Protein-coding gene in the species Homo sapiens

AP-3 complex subunit beta-2 is a protein that in humans is encoded by the AP3B2 gene.

<span class="mw-page-title-main">PNMA2</span> Mammalian protein found in Homo sapiens

Paraneoplastic antigen Ma2 is a protein that in humans is encoded by the PNMA2 gene.

<span class="mw-page-title-main">ELAV-like protein 3</span> Protein-coding gene in the species Homo sapiens

ELAV-like protein 3 is a protein that in humans is encoded by the ELAVL3 gene.

<span class="mw-page-title-main">Gerald Fischbach</span> American physician and neuroscientist (born 1938)

Gerald D. Fischbach is an American neuroscientist. He received his M.D. from the Weill Cornell Medical College of Cornell University in 1965 before beginning his research career at the National Institutes of Health in 1966, where his research focused on the mechanisms of neuromuscular junctions. After his tenure at the National Institutes of Health, Fischbach was a professor at Harvard University Medical School from 1972 to 1981 and from 1990 to 1998 and the Washington University School of Medicine from 1981 to 1990. In 1998, he was named the director of the National Institute of Neurological Disorders and Stroke before becoming the Vice President and Dean of the Health and Biomedical Sciences, the Dean of the Faculty of Medicine, and the Dean of the Faculty of Health Sciences at Columbia University from 2001 to 2006. Gerald Fischbach currently serves as the scientific director overseeing the Simons Foundation Autism Research Initiative. Throughout Fischbach's career, much of his research has focused on the formation and function of the neuromuscular junction, which stemmed from his innovative use of cell culture to study synaptic mechanisms.

High-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP) is a variant of CLIP for genome-wide mapping protein–RNA binding sites or RNA modification sites in vivo. HITS-CLIP was originally used to generate genome-wide protein-RNA interaction maps for the neuron-specific RNA-binding protein and splicing factor NOVA1 and NOVA2; since then a number of other splicing factor maps have been generated, including those for PTB, RbFox2, SFRS1, hnRNP C, and even N6-Methyladenosine (m6A) mRNA modifications.

Rosalind Anne Segal is an American neurobiologist. She is a Professor of Neurobiology at Harvard Medical School and the Co-Chair of the Cancer Biology Department at the Dana Farber Cancer Institute. Segal's work employs modern methods of cell and molecular biology to study the development of the mammalian brain with the goal of understanding how disruption of this normal process leads to the formation of brain malignancies.

<span class="mw-page-title-main">New York Genome Center</span> Research organization in New York, United States

The New York Genome Center (NYGC) is an independent 501(c)(3) nonprofit academic research institution in New York, New York. It serves as a multi-institutional collaborative hub focused on the advancement of genomic science and its application to drive novel biomedical discoveries. NYGC's areas of focus include the development of computational and experimental genomic methods and disease-focused research to better understand the genetic basis of cancer, neurodegenerative disease, and neuropsychiatric disease. In 2020, the NYGC also has directed its expertise to COVID-19 genomics research.

<span class="mw-page-title-main">Nina Papavasiliou</span> Immunologist

Nina Papavasiliou is an immunologist and Helmholtz Professor in the Division of Immune Diversity at the German Cancer Research Center in Heidelberg, Germany. She is also an adjunct professor at the Rockefeller University, where she was previously associate professor and head of the Laboratory of Lymphocyte Biology. She is best known for her work in the fields of DNA and RNA editing.

<span class="mw-page-title-main">Cerebellar degeneration</span> Medical condition

Cerebellar degeneration is a condition in which cerebellar cells, otherwise known as neurons, become damaged and progressively weaken in the cerebellum. There are two types of cerebellar degeneration; paraneoplastic cerebellar degeneration, and alcoholic or nutritional cerebellar degeneration. As the cerebellum contributes to the coordination and regulation of motor activities, as well as controlling equilibrium of the human body, any degeneration to this part of the organ can be life-threatening. Cerebellar degeneration can result in disorders in fine movement, posture, and motor learning in humans, due to a disturbance of the vestibular system. This condition may not only cause cerebellar damage on a temporary or permanent basis, but can also affect other tissues of the central nervous system, those including the cerebral cortex, spinal cord and the brainstem.

<span class="mw-page-title-main">Priya Rajasethupathy</span> Neuroscientist

Priya Rajasethupathy is a neuroscientist and assistant professor at the Rockefeller University, leading the Laboratory of Neural Dynamics and Cognition.

Anne Schaefer is a neuroscientist, professor of Neuroscience, vice-chair of Neuroscience, and director of the Center for Glial Biology at the Icahn School of Medicine at Mount Sinai in New York City. Schaefer investigates the epigenetic mechanisms of cellular plasticity and their role in the regulation of microglia-neuron interactions. Her research is aimed at understanding the mechanisms underlying various neuropsychiatric disorders and finding novel ways to target the epigenome therapeutically.

References

  1. 1 2 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. 18 September 2018. Retrieved 21 January 2019.
  3. ↑ "Archived copy" (PDF). Archived from the original (PDF) on 2019-01-21. Retrieved 2019-01-13.{{cite web}}: CS1 maint: archived copy as title (link)
  4. 1 2 "NINDS Research Program Award (R35) Recipients FY 2017 - National Institute of Neurological Disorders and Stroke". www.ninds.nih.gov. Retrieved 21 January 2019.
  5. 1 2 "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". The New York Times. Retrieved 21 January 2019.
  7. ↑ "The Rockefeller University Hospital". rockefeller.edu. Archived from the original on 24 December 2015. 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. 1 2 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. S2CID   12989492.
  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 (Press release). 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. 20 January 2016. 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. Oxford University Press, USA. ISBN   978-0199772735.
  30. ↑ "New 2019 Academy Members Announced". American Academy of Arts & Sciences. 17 April 2019. Retrieved 2019-06-20.
  31. ↑ Millner-Fairbanks, Amanda (4 December 2007). "Girls Make History by Sweeping Top Honors at a Science Contest". The New York Times. Retrieved 21 January 2019.
  32. ↑ Following in family’s footsteps, Alicia Darnell wins national science prize
  33. ↑ Kates, Joan Giangrasse (3 July 2016). "Gilda Barston, cellist and teacher, dies at 71". chicagotribune.com. Retrieved 2019-01-14.
  34. ↑ "Ardyth Alton-Juilliard Pre-College Faculty". 11 March 2008.
  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. Archived from the original on 2018-09-13. 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. 18 September 2018. Retrieved 21 January 2019.
  43. ↑ "2014 New Members and Foreign Associates Elected". www.nasonline.org. Archived from the original on August 18, 2015.
  44. ↑ "Darnell receives Columbia/NY Presbyterian Award as Leader of NY Genome Center" (PDF). www.nygenome.org. Archived from the original (PDF) on 2019-01-21. 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. ↑ "New 2019 Academy Members Announced". 17 April 2019.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.