Research

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Jonathan  Lipton, MD, PhD

Jonathan Lipton MD
Research Center:
F.M. Kirby Neurobiology Center
Program:
Neurobiology Program
Department:
Neurology Research
Hospital Title:
Research Associate in Neurology
Academic Title:
Instructor of Neurology, Harvard Medical School
Research Focus Area:
Circadian RhythmsNeurological DiseaseTranslation
Contact:
617-919-2749
Contact Via Email
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Research Overview

The rotation of the Earth subjects terrestrial organisms to daily light/dark cycles. To keep in sync with these geophysical oscillations, we have evolved a biological timing system that segregates our behavior, physiology, and metabolism with circadian – or nearly 24 hour (from circa diem, ‘about a day’) – rhythmicity. The circadian timekeeping system is a prediction mechanism that synchronizes internal organismal state with the external environment. While the central clock resides in the brain, all our cells have circadian clocks. Disruption of circadian rhythms is extraordinarily common in modern society and has been linked with neurological disease, metabolic disease, cancer, and aging.

Our research seeks to understand the fundamental relationships between the circadian clock and diseases of the developing brain. We have identified the core circadian clock protein BMAL1 as a regulator of protein synthesis (i.e. translation) (Cell, 2015). BMAL1 promotes circadian rhythms in protein synthesis as a substrate of the mechanistic target of rapamycin (mTOR) pathway, a critical gauge of nutritive status and stress. We have characterized a novel, potentially modifiable link between the circadian timing system and cellular signaling.

One of our major goals is the identification of the mechanisms of circadian-regulated protein synthesis in neural and non-neural cells. How are rhythms of protein synthesis generated? How does protein synthesis coordinate circadian timekeeping? What is the signaling logic that dictates which proteins are made at which time of day? How do circadian rhythms affect protein synthesis in neurons? How do circadian clocks in the brain impact neural function? How are these mechanisms disrupted in neurological disease models?

We utilize and develop animal models, cell-based reporter assays, live cell imaging, behavioral assays, and biochemistry to address fundamental questions of circadian timing, translation, and neurological function with our gaze focused on diseases of the nervous system.

About Jonathan Lipton

Jonathan Lipton is a New York City native who received his MD and PhD degrees from the Albert Einstein College of Medicine, performing graduate work with Scott Emmons studying the genetics of motivational behavior. After a residency and chief residency in Child Neurology and fellowship in Sleep Medicine at Boston Children’s Hospital and Harvard Medical School, he completed post-doctoral studies with Mustafa Sahin, investigating circadian rhythm dysfunction in models of neurodevelopmental disease. He has been supported by the Howard Hughes Medical Institute, Shore Foundation, Tuberous Sclerosis Alliance, Hearst Foundation, American Academy of Neurology, American Sleep Medicine Foundation, and the NIH.

Publications

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  1. Lipton JO, Yuan ED, Boyle LM, Ebrahimi-Fakhari D, Kwiatkowski E, Nathan A, Güttler T, Davis F, Asara JM, Sahin M. The Circadian Protein BMAL1 Regulates Translation in Response to S6K1-Mediated Phosphorylation. Cell. 2015 May 21; 161(5):1138-51.
  2. Lipton JO, Sahin M. The neurology of mTOR. Neuron. 2014 Oct 22; 84(2):275-91.
  3. Olson H, Shen Y, Avallone J, Sheidley BR, Pinsky R, Bergin AM, Berry GT, Duffy FH, Eksioglu Y, Harris DJ, Hisama FM, Ho E, Irons M, Jacobsen CM, James P, Kothare S, Khwaja O, Lipton J, Loddenkemper T, Markowitz J, Maski K, Megerian JT, Neilan E, Raffalli PC, Robbins M, Roberts A, Roe E, Rollins C, Sahin M, Sarco D, Schonwald A, Smith SE, Soul J, Stoler JM, Takeoka M, Tan WH, Torres AR, Tsai P, Urion DK, Weissman L, Wolff R, Wu BL, Miller DT, Poduri A. Copy number variation plays an important role in clinical epilepsy. Ann Neurol. 2014 Jun; 75(6):943-58.
  4. Lipton J, Sahin M. Fragile X syndrome therapeutics: translation, meet translational medicine. Neuron. 2013 Jan 23; 77(2):212-3.
  5. Lipton J, Rivkin MJ. 16p11.2-related paroxysmal kinesigenic dyskinesia and dopa-responsive parkinsonism in a child. Neurology. 2009 Aug 11; 73(6):479-80.
  6. Lipton J, Megerian JT, Kothare SV, Cho YJ, Shanahan T, Chart H, Ferber R, Adler-Golden L, Cohen LE, Czeisler CA, Pomeroy SL. Melatonin deficiency and disrupted circadian rhythms in pediatric survivors of craniopharyngioma. Neurology. 2009 Jul 28; 73(4):323-5.
  7. Lipton J, Becker RE, Kothare SV. Insomnia of childhood. Curr Opin Pediatr. 2008 Dec; 20(6):641-9.
  8. Lipton J, Joffe S, Ullrich NJ. CNS relapse of acute myelogenous leukemia masquerading as pseudotumor cerebri. Pediatr Neurol. 2008 Nov; 39(5):355-7.
  9. Jonathan Lipton and Michael J. Rivkin. Kawasaki disease: cerebrovascular and neurologic complication. Uncommon Causes of Stroke. 2008.
  10. Lipton, J. and Rivkin, M.J. Kawasaki disease: cerebrovascular and neurologic complications. Uncommon Causes of Stroke (editor LR Caplan). 2008.
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  12. Jonathan O. Lipton, Yoon-Jae Cho, Jonathan T. Megerian, Theresa Shanahan, Laurie Cohen, Richard Ferber, Charles Czeisler, Sanjeev V. Kothare, Scott L. Pomeroy. Disruption of Circadian Melatonin Secretion in Pediatric Craniopharyngioma Survivors with Hypersomnolence. Sleep (Abstract). 2008.
  13. Lipton, J. . Mating worms and the cystic kidney: C. elegans as a model for renal disease. Pediatric Nephrology. 2005; 20:1531-36.
  14. Lipton, J. , Kleemann, G., Ghosh, R., Lints, R., Emmons, S.W. . Mate searching in Caenorhabditis elegans: a genetic model for sex drive in a simple in vertebrate. Journal of Neuroscience. 2004; 24:7427-34.
  15. Emmons, S.W. and Lipton, J. The genetic basis of male mating behavior. Journal of Neurobiology. 2003; 54:93-110.
  16. Jonathan Oren Lipton. Genetics of Sexually Motivated Behavior in Caenorhabditis elegans. 2003.
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RELATED RESEARCH CENTER

F.M. Kirby Neurobiology Center

The F.M. Kirby Neurobiology Center, together with the Neurobiology Program at Boston Children’s Hospital, is the largest basic neuroscience research enterprise at a U.S. hospital. It incorporates basic and translational neuroscience research, focusing primarily on developmental neurobiology.

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