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Dr. Gladys Ko

Research

Dr. Gladys Ko

The research interests of our lab are functional regulation of ion channels, synaptic plasticity, and cicadian biology in both healthy and disease states.  There are two major lines of research in our lab.

A. Circadian regulation of ion channel physiology and function in the retina and heart in healthy and diabetic states.

Misalignment of internal circadian clocks with the external time-cue, such as happening in the shift-workers and frequent across-time-zone travelers, greatly increases the risks of metabolic syndromes (i.e. diabetes, cardiovascular diseases), sleep disorders, and cancers.  In animals, disruption of circadian clocks speeds up aging process, impairs visual function, and causes diabetes, cardiovascular diseases and cancers.  We have characterized the molecular mechanisms as how intrinsic circadian clocks modulate the apparent affinity of cGMP-gated ion channels (CNGCs) and regulate the protein expression of L-type voltage-gated calcium channels (L-VGCCs).  Both ion channels (CNGCs and L-VGCCs) are essential in the visual processing in the retina, as well as cardiac physiology.  We discover that both post-transcriptional regulation via microRNAs and post-translational regulation via various signaling pathways are involved in the circadian regulation of L-VGCCs and CNGCs in retinal photoreceptors and cardiomyocytes.  The circadian rhythms of L-VGCCs are important in regulating melatonin and glutamate release and retinoschisin secretion from photoreceptors.  Circadian regulation of CNGCs is important in photoreceptor light sensitivity. 

Diabetic retinopathy is one major problem associated with diabetes.  Nearly all type I and 60% type II diabetic patients will develop diabetic retinopathy, a major cause of blindness in American working adults.  Mutations in one of the circadian clock genes cause diabetes and premature aging in animal models.  And, chronic diabetic conditions also disturb the circadian rhythms in the retina.  We are investigating how early diabetic conditions affect retinal physiology and function at the cellular and molecular levels.

Biological Clock

B. Characterization of a novel bioactive peptide, peptide Lv.

Our lab recently discovered a novel bioactive peptide, peptide Lv.  Peptide Lv natually exists in many tissues, including the eye, brain, heart, spleen, lung, and intestines.  We found that peptide Lv regulates L-VGCC activities in the retina and heart through various intracellualr signaling pathways.  We are now investigating the physiological functions of peptide Lv both in the retina and heart.

 

Students and post-docs joining the lab will learn various techniques, including patch-clamp electrophysiological recordings, electroretinogram (ERG), Western immunoblotting, immunohistochemistry and immunocytochemistry (confocal imaging), quantitative RT-PCR, high performance liquid chromatography (HPLC), gene transfections (knock-down or knock-in), and other molecular techniques in addition to the basic research laboratory techniques.

Teaching

  • VIBS / NRSC 277 - Introduction to Neuroscience (3 credit hours)
  • VIBS / NRSC 450 H - Mammalian Functional Neuroanatomy (4 credit hours)
  • VIBS 485 - Directed Studies: Undergraduate Studies
  • VIBS 491 - Undergraduate Research
  • BIOL / NRSC 601 - Biological Clocks
  • VIBS 684 - Professional Internship
  • VIBS 685 - Directed Studies: Graduate Studies
  • VIBS 691 - Graduate Research
  • VIBS / NRSC 603 - Neuroanatomy (in the past)

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