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Research Overview

Our lab asks how light drives functions that are as diverse as visual perception, sleep regulation, hormonal control, and setting of the internal body clock. We pose this question for species that occupy distinct ecological niches to learn how visual mechanisms are tailored to different behavioral needs. Our research spans organizational levels and time scales, from molecules to circuits and from milliseconds to hours. It centers on electrophysiological and optical techniques that are applied in vitro and in vivo.

Visual performance is remarkable. Perception can be elicited by a handful of photons, yet continues when the light level has intensified by many orders of magnitude. How is this dynamic range established? In cases of severe blindness where visual awareness is lost, light can still keep the body clock and hormone levels in register with the solar cycle. What are the origins of this robustness?

Questions of dynamic range, robustness, and other parameters of system operation recur throughout the biological sciences. We pose them in the visual system, where the input (light) can be precisely controlled and its effects can be quantified at levels ranging from the conformational changes of molecules to alterations in behavior. We seek connections between these levels.

We focus on two aspects of the visual system. The first is the fovea, a retinal specialization that initiates most visual perception in humans and other primates but is found in no other mammal. We seek to understand how the fovea supports the exceptional visual acuity of primates, which is 10-fold higher than that of cats and 100-fold higher than that of mice. The second concerns unusual photoreceptors; these are not the classical rods and cones, but a population of retinal output neurons that capture light with a molecule called melanopsin. Signals from these intrinsically photosensitive retinal ganglion cells (ipRGCs) largely bypass consciousness while exerting a broad influence on physiology. We study the mechanisms of signal generation by ipRGCs and interpret them in the context of downstream circuits in the retina and brain.

An understanding of the visual system provides the foundation for maintaining its health, detecting disease, and developing methods to forestall and reverse blindness.

About Michael Do

Michael Tri H. Do is a member of the F.M. Kirby Neurobiology Center at Boston Children's Hospital and an Assistant Professor of Neurology at Harvard Medical School. His postdoctoral work, done with King-Wai Yau at the Johns Hopkins University School of Medicine, concerned an unusual type of mammalian photoreceptor that sends information directly from the retina to the brain. He completed his Ph.D. with Bruce Bean at Harvard Medical School, investigating the origin of electrical activity in certain cells of the basal ganglia. As an undergraduate at Georgetown University, he worked with Susette Mueller to learn how some types of cancer cells grow and spread more effectively than others.

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Researcher Areas

  • Regulation of Physiology and Behavior by Light
  • Perception and Physiological Control

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PUBLICATIONS

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  1. Do MTH. Mixed Palettes of Melanopsin Phototransduction. Cell. 2018 Oct 18; 175(3):637-639. View abstract
  2. Emanuel AJ, Kapur K, Do MTH. Biophysical Variation within the M1 Type of Ganglion Cell Photoreceptor. Cell Rep. 2017 Oct 24; 21(4):1048-1062. View abstract
  3. Milner ES, Do MTH. A Population Representation of Absolute Light Intensity in the Mammalian Retina. Cell. 2017 Nov 02; 171(4):865-876.e16. View abstract
  4. Do MTH. The outer and inner halves of photoreceptor adaptation. J Physiol. 2017 Jun 01; 595(11):3247-3248. View abstract
  5. Emanuel AJ, Do MT. Melanopsin tristability for sustained and broadband phototransduction. Neuron. 2015 Mar 04; 85(5):1043-55. View abstract
  6. 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. View abstract
  7. 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 09; 31(45):16094-101. View abstract
  8. 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. View abstract
  9. 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 01; 518(23):4813-24. View abstract
  10. Do MT, Yau KW. Intrinsically photosensitive retinal ganglion cells. Physiol Rev. 2010 Oct; 90(4):1547-81. View abstract
  11. 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. View abstract
  12. Fu Y, Liao HW, Do MT, Yau KW. Non-image-forming ocular photoreception in vertebrates. Curr Opin Neurobiol. 2005 Aug; 15(4):415-22. View abstract
  13. Do MT, Bean BP. Sodium currents in subthalamic nucleus neurons from Nav1.6-null mice. J Neurophysiol. 2004 Aug; 92(2):726-33. View abstract
  14. Do MT, Bean BP. Subthreshold sodium currents and pacemaking of subthalamic neurons: modulation by slow inactivation. Neuron. 2003 Jul 03; 39(1):109-20. View abstract
  15. 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. View abstract
  16. 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. View abstract