Research

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Michael  Do, PhD

Michael Do
Lab:
Do Laboratory
Research Center:
F.M. Kirby Neurobiology Center
Program:
Neurobiology Program
Department:
Neurology Research
Hospital Title:
Research Associate
Academic Title:
Assistant Professor, Harvard Medical School
Research Focus Area:
Regulation of Physiology and Behavior by Light
Contact:
617-919-2509
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Research Overview

So much of our experience is visual, it can be surprising to learn that light controls widespread functions -- including the circadian rhythm, sleep, locomotion, and the pupillary light reflex -- without impinging on awareness. Rods and cones, long believed to be the only mammalian photoreceptors, are not required. 

This "non-image vision" is mediated largely by the intrinsically photosensitive retinal ganglion cells (ipRGCs), newly discovered photoreceptors that capture light with a pigment, melanopsin, and directly drive neurons in the retina and over a dozen brain regions. The widespread influence of non-image vision is reflected in the many diseases associated with its dysfunction. For instance, ipRGCs are the principal means of synchronizing the circadian clock with local time, and dysregulation of the clock has been implicated in poor mental health, metabolic disorders, cancer, and cardiovascular disease. 

Our overarching interest is how organisms regulate their behavior according to the environment. Non-image vision provides a rigorous paradigm for tracking an environmental signal all the way to motor output. The signal, ambient light, can be precisely matched for behaving animals and in vitro experiments. The intact circuitry of the retina is accessible with minimal perturbation. Non-image behaviors are readily measured, while their diversity allows investigation of signal processing across numerous brain regions. 

Importantly, ipRGCs are selectively manipulable through the melanopsin promoter, and the influence of ipRGCs on the whole animal can be isolated using established mouse models with rods and cones disabled. These features allow us to take a quantitative approach to understanding the system. We use electrophysiology and imaging on transgenic mice and tissues to connect biophysical mechanisms to behavior. 

About Michael Do

Michael Do received his PhD in Neurobiology from Harvard University, where he studied with Bruce P. Bean how neurons of the subthalamic nucleus generate rhythmic activity without any external influence. He then joined King-Wai Yau at the Johns Hopkins University School of Medicine to investigate newly discovered photoreceptors in the mammalian eye that are critical to "non-image" visual functions such as regulation of the circadian clock and of sleep. 

Dr. Do does basic research on biological mechanisms that are important to health and disease. He has been supported by fellowships from the Howard Hughes Medical Institute and National Eye Institute, and recognized by awards from the Johns Hopkins School of Medicine and Federation of American Societies for Experimental Biology.

Publications

Publications powered by Harvard Catalyst Profiles
  1. Emanuel AJ, Do MT. Melanopsin tristability for sustained and broadband phototransduction. Neuron. 2015 Mar 4; 85(5):1043-55.
  2. Do MT, Yau KW. Adaptation to steady light by intrinsically photosensitive retinal ganglion cells. Proc Natl Acad Sci U S A. 2013 Apr 30; 110(18):7470-5.
  3. Xue T, Do MT, Riccio A, Jiang Z, Hsieh J, Wang HC, Merbs SL, Welsbie DS, Yoshioka T, Weissgerber P, Stolz S, Flockerzi V, Freichel M, Simon MI, Clapham DE, Yau KW. Melanopsin signalling in mammalian iris and retina. Nature. 2011 Nov 02; 479(7371):67-73.
  4. Do MT, Yau KW. Intrinsically photosensitive retinal ganglion cells. Physiol Rev. 2010 Oct; 90(4):1547-81.
  5. Do MT, Bean BP. Sodium currents in subthalamic nucleus neurons from Nav1.6-null mice. J Neurophysiol. 2004 Aug; 92(2):726-33.
  6. Do MT, Bean BP. Subthreshold sodium currents and pacemaking of subthalamic neurons: modulation by slow inactivation. Neuron. 2003 Jul 3; 39(1):109-20.
  7. Coopman PJ, Do MT, Thompson EW, Mueller SC. Phagocytosis of cross-linked gelatin matrix by human breast carcinoma cells correlates with their invasive capacity. Clin Cancer Res. 1998 Feb; 4(2):507-15.
  8. Do MT, Kang SH, Xue T, Zhong H, Liao HW, Bergles DE, Yau KW. Photon capture and signalling by melanopsin retinal ganglion cells. Nature. 2009 Jan 15; 457(7227):281-7.
  9. Fu Y, Liao HW, Do MT, Yau KW. Non-image-forming ocular photoreception in vertebrates. Curr Opin Neurobiol. 2005 Aug; 15(4):415-22.
  10. Coopman PJ, Do MT, Barth M, Bowden ET, Hayes AJ, Basyuk E, Blancato JK, Vezza PR, McLeskey SW, Mangeat PH, Mueller SC. The Syk tyrosine kinase suppresses malignant growth of human breast cancer cells. Nature. 2000 Aug 17; 406(6797):742-7.
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  12. Schmidt TM, Do MT, Dacey D, Lucas R, Hattar S, Matynia A. Melanopsin-positive intrinsically photosensitive retinal ganglion cells: from form to function. J Neurosci. 2011 Nov 9; 31(45):16094-101.
  13. Müller LP, Do MT, Yau KW, He S, Baldridge WH. Tracer coupling of intrinsically photosensitive retinal ganglion cells to amacrine cells in the mouse retina. J Comp Neurol. 2010 Dec 1; 518(23):4813-24.
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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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