Dr. Darnell studies RNA biology and next-generation human genomics, work that arose from his clinical and basic studies of patients with paraneoplastic neurologic disorders (PNDs). PNDs are a group of rare brain diseases thought to arise when tumors – typically breast, ovarian, or lung cancers – start making proteins that are normally only made by the brain. This leads to immune responses against these proteins–first against the tumors, and then, spreading to an auto-immune attack, to the brain itself.
Using a combination of immunologic, biochemical and genetic approaches, Dr. Darnell’s lab is investigating how these antitumor and autoimmune responses develop in PND patients. This work led to insights into mechanisms of antigen cross-presentation and subsequent clinical tumor vaccine trials as well as innovative means of specifically killing those antigen specific T cells that mediate autoimmune disease.
Studies of the PNDs also led the Darnell laboratory to identify and characterize the first human neuron-specific RNA binding proteins. The lab did this through detailed biochemical studies, complemented by the development of methods to understand how RNA regulation goes awry in vivo, in human brain and cancer specimens. The laboratory developed CLIP, a method for the functional annotation of RNA regulation analogous to DNA ChIP that has great sensitivity and specificity, and is now the gold standard for understanding RNA regulation in vivo. CLIP studies have been used to bring biologic insight into the mechanisms underlying how neurons develop and function, how micro-RNA’s bind to and specific RNAs, and how RNA regulation underlies many human diseases, including intellectual disability, autism, epilepsy, muscular dystrophy and cancer, bringing the Darnell laboratory into the cutting edge of modern clinical genomics.
Dr. Darnell’s research contributions have been acknowledged by his appointment as a Howard Hughes Medical Institute Investigator since 2002 and as the Heilbrunn Professor of Cancer Biology at The Rockefeller University, where he has been since 1992. In November 2012 he joined the New York Genome Center, served as its CEO for four years, and remains Founding Director. He is Senior Physician at the Rockefeller University Hospital and an Adjunct Attending Neuro-Oncologist at the Memorial Sloan Kettering Cancer Center, an Elected Member of the Institute of Medicine of the National Academy of Sciences, a Member of the Association of American Physicians, and a Fellow of the American Association for the Advancement of Science. He has received numerous awards, including the Derek Denny-Brown Neurological Scholar Award, the Burroughs Wellcome Clinical Scientist Award in Translational Research, an NIH Directors Transformative Research Award in 2012, and NIH Outstanding Investigator Award in 2016. Dr. Darnell served on the Board of Scientific Counselors of the Jackson Laboratory and currently serves on the NINDS Advisory Council and the Roundtable on Translating Genomic-Based Research for Health of the Institute of Medicine.
Robert B. Darnell, M.D., PhD
New York Genome Center Founding Director Robert B. Darnell, MD, PhD, is the Robert and Harriet Heilbrunn Professor and Senior Attending Physician at The Rockefeller University and an Investigator at the Howard Hughes Medical Institute. In 2014 he was elected a Member of the National Academy of Sciences and has been a Member of the National Academy of Medicine since 2010. He is also member of the Association of American Physicians and a Fellow of the American Association for the Advancement of Science. He has received numerous awards, including the Derek Denny-Brown Young Neurological Scholar Award, the Burroughs Wellcome Fund Clinical Scientist Award in Translational Research, the NIH Director’s Transformative Research Award in 2012, and an NIH Outstanding Investigator Award in 2016.
Dr. Darnell’s academic work began with studies of patients with rare disorders triggered by naturally occurring anti-tumor immune responses that he discovered are caused by antigen-specific killer T cells, laying the groundwork for the field of immuno-oncology. His analysis of the target antigens led him to discover brain-specific systems governing the regulation of RNA, the transcribed copies of our genes. He developed CLIP, a new platform technology that is being widely applied in neurobiology, cancer and inflammatory disease.
At the New York Genome Center (NYGC), Dr. Darnell’s work has been focused on harnessing the revolution created by the recent dramatic cost reduction in genomic sequencing as well as rapidly advancing information and other technology, utilizing those advances to transform healthcare. He works with the 12 Institutional Founding Members and a growing list of Associate Members from academia and industry, including IBM, to help develop tools capable of analyzing the massive amounts of data genomic sequencing produces into clinically actionable outcomes. He is Principal Investigator on NYGC’s NIH Center for Common Disease Genomics Grant from the National Human Genome Research Institute, the Accelerating Medicines Partnership grant from the National Institute of Arthritis and Musculoskeletal Diseases, and the Sohn Foundation Grant for Pediatric Cancer Research. Dr. Darnell has studied and worked at a number of the NYGC’s Institutional Founding Members, including Columbia University, The Mount Sinai School of Medicine, Weill Cornell Medicine, Memorial Sloan Kettering Cancer Center, The Jackson Laboratory and The Rockefeller University. As Founding Director, he was involved with the growth and advancement of the NYGC since its inception in 2010, and was a member of the original group of New York scientists that helped to shape NYGC’s early direction.
Turner TN, Hormozdiari F, Duyzend MH, McClymont SA, Hook PW, Iossifov I, Raja A, Baker C, Hoekzema K, Stessman HA, Zody MC, Nelson BJ, Huddleston J, Sandstrom R, Smith JD, Hanna D, Swanson JM, Faustman EM, Bamshad MJ, Stamatoyannopoulos J, Nickerson DA, McCallion AS, Darnell R, Eichler EE.Genome Sequencing of Autism-Affected Families Reveals Disruption of Putative Noncoding Regulatory DNA
Am J Hum Genet. 2016 Jan 7;98(1):58-74. doi: 10.1016/j.ajhg.2015.11.023. Epub 2015 Dec 31. PMID: 26749308
Scheckel C, Drapeau E, Frias MA, Park CY, Fak J, Zucker-Scharff I, Kou Y, Haroutunian V, Ma’ayan A, Buxbaum JD, Darnell RBRegulatory consequences of neuronal ELAV-like protein binding to coding and non-coding RNAs in human brain
Elife. 2016 Feb 19;5. pii: e10421. doi: 10.7554/eLife.10421. PMID: 26894958
Hwang HW, Park CY, Goodarzi H, Fak JJ, Mele A, Moore MJ, Saito Y, Darnell RBPAPERCLIP Identifies MicroRNA Targets and a Role of CstF64/64tau in Promoting Non-canonical poly(A) Site Usage
Cell Rep. 2016 Mar 30. pii: S2211-1247(16)30264-9. doi: 10.1016/j.celrep.2016.03.023. [Epub ahead of print] PMID: 27050522