Zhuo-Hua Pan

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Zhuo-Hua Pan
潘卓华
Born1956 (age 6667)
EducationJinhua No. 1 High School
University of Science and Technology of China
State University of New York at Buffalo
Scientific career
Fields Neuroscience
Institutions Wayne State University
Chinese name
Traditional Chinese
Simplified Chinese

Zhuo-Hua Pan (Chinese :潘卓华; pinyin :Pān Zhuóhuá; born 1956) is a Chinese-American neuroscientist, known for his foundational contributions to optogenetics. [1] [2] He is the Edward T. and Ellen K. Dryer Endowed Professor of Ophthalmology at Wayne State University, and Scientific Director of the Ligon Research Center of Vision at the university's Kresge Eye Institute.

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Education and career

Pan was born 1956 in Pujiang County of Jinhua, Zhejiang, China. [3] After graduating from Jinhua No. 1 High School, he entered the University of Science and Technology of China in 1978 and earned his B.S. degree in 1982. [4] He earned his M.S. in 1984 from the Institute of Biophysics, Chinese Academy of Sciences, and became an instructor at Zhejiang University afterwards. [5]

In 1986, he moved to the United States to further his studies at the State University of New York at Buffalo. He earned his Ph.D. in 1990 and conducted postdoctoral research for another year. [5]

From 1991 to 1997 he was an instructor of neurology at Harvard Medical School and Boston Children's Hospital. In 1998, he became an assistant professor of neurosurgery at Harvard and Brigham and Women's Hospital. He moved to Wayne State University School of Medicine in 1999, and was promoted to associate professor in 2003 and professor in 2007. [5] In 2011, he was appointed the Edward T. and Ellen K. Dryer Endowed Professor of Ophthalmology and Kresge Eye Institute, and Scientific Director of the Ligon Research Center of Vision. [5]

Optogenetics

In the early 2000s, Pan envisioned implanting a light-sensitive protein, which converts light to electrical signals for neurons, into the eye to cure blindness. The method is now known as optogenetics. [1] In the summer of 2004, he used a virus carrying the channelrhodopsin DNA to infect the ganglion cells in the eyes of blind mice, and successfully detected electrical activity when the cells were stimulated with light, a "revolutionary" first step in potentially restoring eyesight to the blind. [1]

Pan and his collaborator, Alexander Dizhoor, submitted their paper reporting their work to Nature in November 2004. However, they were directed to the specialized journal Nature Neuroscience , which rejected the paper. In early 2005, they submitted it to the Journal of Neuroscience , but were again rejected. [1] In May 2005, Pan presented his work at the Association for Research in Vision and Ophthalmology conference in Florida, which became the clearest public evidence of his invention. [1]

Around the same time, other scientists around the world were doing similar research to Pan. In August 2005, Nature Neuroscience, the same journal that had rejected Pan's paper, published a paper by Stanford University scientists Edward Boyden and Karl Deisseroth describing their work using channelrhodopsin to make neurons detect light. [1] Their research was hailed as a major breakthrough and caught the attention of mainstream media including The New York Times . When the journal Neuron finally published Pan's paper in April 2006, it was met with indifference. [1]

Boyden and Deisseroth have since been rewarded with major grants and prizes, including The Brain Prize and the 2015 Breakthrough Prize in Life Sciences with a $3 million prize for each scientist, [1] while Pan only won awards from his own university. [1] In 2016, Stat News published a report which credits Pan as the inventor of optogenetics and brought attention to his contributions. [2]

RetroSense Therapeutics

Based on Pan's research, Sean Ainsworth started the company RetroSense Therapeutics in 2009. The company develops treatment for the genetic disease retinitis pigmentosa, which causes blindness and affects about 100,000 people in the United States. [6] In 2016, Allergan bought RetroSense for $60 million. [6]

Publications

Source: [5]

Related Research Articles

<span class="mw-page-title-main">Retina</span> Part of the eye

The retina is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then processes that image within the retina and sends nerve impulses along the optic nerve to the visual cortex to create visual perception. The retina serves a function which is in many ways analogous to that of the film or image sensor in a camera.

<span class="mw-page-title-main">Visual system</span> Body parts responsible for sight

The visual system comprises the sensory organ and parts of the central nervous system which gives organisms the sense of sight as well as enabling the formation of several non-image photo response functions. It detects and interprets information from the optical spectrum perceptible to that species to "build a representation" of the surrounding environment. The visual system carries out a number of complex tasks, including the reception of light and the formation of monocular neural representations, colour vision, the neural mechanisms underlying stereopsis and assessment of distances to and between objects, the identification of a particular object of interest, motion perception, the analysis and integration of visual information, pattern recognition, accurate motor coordination under visual guidance, and more. The neuropsychological side of visual information processing is known as visual perception, an abnormality of which is called visual impairment, and a complete absence of which is called blindness. Non-image forming visual functions, independent of visual perception, include the pupillary light reflex and circadian photoentrainment.

<span class="mw-page-title-main">Retinitis pigmentosa</span> Gradual retinal degeneration leading to progressive sight loss

Retinitis pigmentosa (RP) is a genetic disorder of the eyes that causes loss of vision. Symptoms include trouble seeing at night and decreasing peripheral vision. As peripheral vision worsens, people may experience "tunnel vision". Complete blindness is uncommon. Onset of symptoms is generally gradual and often begins in childhood.

<span class="mw-page-title-main">Photoreceptor cell</span> Type of neuroepithelial cell

A photoreceptor cell is a specialized type of neuroepithelial cell found in the retina that is capable of visual phototransduction. The great biological importance of photoreceptors is that they convert light into signals that can stimulate biological processes. To be more specific, photoreceptor proteins in the cell absorb photons, triggering a change in the cell's membrane potential.

<span class="mw-page-title-main">Retinal ganglion cell</span> Type of cell within the eye

A retinal ganglion cell (RGC) is a type of neuron located near the inner surface of the retina of the eye. It receives visual information from photoreceptors via two intermediate neuron types: bipolar cells and retina amacrine cells. Retina amacrine cells, particularly narrow field cells, are important for creating functional subunits within the ganglion cell layer and making it so that ganglion cells can observe a small dot moving a small distance. Retinal ganglion cells collectively transmit image-forming and non-image forming visual information from the retina in the form of action potential to several regions in the thalamus, hypothalamus, and mesencephalon, or midbrain.

<span class="mw-page-title-main">Retina bipolar cell</span> Type of neuron

As a part of the retina, bipolar cells exist between photoreceptors and ganglion cells. They act, directly or indirectly, to transmit signals from the photoreceptors to the ganglion cells.

<span class="mw-page-title-main">Melanopsin</span> Mammalian protein found in Homo sapiens

Melanopsin is a type of photopigment belonging to a larger family of light-sensitive retinal proteins called opsins and encoded by the gene Opn4. In the mammalian retina, there are two additional categories of opsins, both involved in the formation of visual images: rhodopsin and photopsin in the rod and cone photoreceptor cells, respectively.

Channelrhodopsins are a subfamily of retinylidene proteins (rhodopsins) that function as light-gated ion channels. They serve as sensory photoreceptors in unicellular green algae, controlling phototaxis: movement in response to light. Expressed in cells of other organisms, they enable light to control electrical excitability, intracellular acidity, calcium influx, and other cellular processes. Channelrhodopsin-1 (ChR1) and Channelrhodopsin-2 (ChR2) from the model organism Chlamydomonas reinhardtii are the first discovered channelrhodopsins. Variants that are sensitive to different colors of light or selective for specific ions have been cloned from other species of algae and protists.

<span class="mw-page-title-main">Amacrine cell</span>

Amacrine cells are interneurons in the retina. They are named from the Greek roots a– ("non"), makr– ("long") and in– ("fiber"), because of their short neuronal processes. Amacrine cells are inhibitory neurons, and they project their dendritic arbors onto the inner plexiform layer (IPL), they interact with retinal ganglion cells and/or bipolar cells.

<span class="mw-page-title-main">Retina horizontal cell</span>

Horizontal cells are the laterally interconnecting neurons having cell bodies in the inner nuclear layer of the retina of vertebrate eyes. They help integrate and regulate the input from multiple photoreceptor cells. Among their functions, horizontal cells are believed to be responsible for increasing contrast via lateral inhibition and adapting both to bright and dim light conditions. Horizontal cells provide inhibitory feedback to rod and cone photoreceptors. They are thought to be important for the antagonistic center-surround property of the receptive fields of many types of retinal ganglion cells.

Intrinsically photosensitive retinal ganglion cells (ipRGCs), also called photosensitive retinal ganglion cells (pRGC), or melanopsin-containing retinal ganglion cells (mRGCs), are a type of neuron in the retina of the mammalian eye. The presence of ipRGCs was first suspected in 1927 when rodless, coneless mice still responded to a light stimulus through pupil constriction, This implied that rods and cones are not the only light-sensitive neurons in the retina. Yet research on these cells did not advance until the 1980s. Recent research has shown that these retinal ganglion cells, unlike other retinal ganglion cells, are intrinsically photosensitive due to the presence of melanopsin, a light-sensitive protein. Therefore they constitute a third class of photoreceptors, in addition to rod and cone cells.

Halorhodopsin is a light-gated ion pump, specific for chloride ions, found in archaea known as halobacteria. It is a seven-transmembrane retinylidene protein from microbial rhodopsin family. It is similar in tertiary structure to vertebrate rhodopsins, the pigments that sense light in the retina. Halorhodopsin also shares sequence similarity to channelrhodopsin, another light-driven ion channel. Halorhodopsin contains the essential light-isomerizable vitamin A derivative all-trans-retinal. Due to the intense attention on solving the structure and function of this molecule, halorhodopsin is one of the few membrane proteins whose crystal structure is known.

Optogenetics is a biological technique to control the activity of neurons or other cell types with light. This is achieved by expression of light-sensitive ion channels, pumps or enzymes specifically in the target cells. On the level of individual cells, light-activated enzymes and transcription factors allow precise control of biochemical signaling pathways. In systems neuroscience, the ability to control the activity of a genetically defined set of neurons has been used to understand their contribution to decision making, learning, fear memory, mating, addiction, feeding, and locomotion. In a first medical application of optogenetic technology, vision was partially restored in a blind patient.

The ribbon synapse is a type of neuronal synapse characterized by the presence of an electron-dense structure, the synaptic ribbon, that holds vesicles close to the active zone. It is characterized by a tight vesicle-calcium channel coupling that promotes rapid neurotransmitter release and sustained signal transmission. Ribbon synapses undergo a cycle of exocytosis and endocytosis in response to graded changes of membrane potential. It has been proposed that most ribbon synapses undergo a special type of exocytosis based on coordinated multivesicular release. This interpretation has recently been questioned at the inner hair cell ribbon synapse, where it has been instead proposed that exocytosis is described by uniquantal release shaped by a flickering vesicle fusion pore.

Retinal gene therapy holds a promise in treating different forms of non-inherited and inherited blindness.

<span class="mw-page-title-main">Karl Deisseroth</span> American optogeneticist

Karl Alexander Deisseroth is an American scientist. He is the D.H. Chen Professor of Bioengineering and of psychiatry and behavioral sciences at Stanford University.

<span class="mw-page-title-main">Retinal regeneration</span>

Retinal regeneration refers to the restoration of vision in vertebrates that have suffered retinal lesions or retinal degeneration.

<span class="mw-page-title-main">Douglas G. McMahon</span>

Douglas G. McMahon is a professor of Biological Sciences and Pharmacology at Vanderbilt University. McMahon has contributed several important discoveries to the field of chronobiology and vision. His research focuses on connecting the anatomical location in the brain to specific behaviors. As a graduate student under Gene Block, McMahon identified that the basal retinal neurons (BRNs) of the molluscan eye exhibited circadian rhythms in spike frequency and membrane potential, indicating they are the clock neurons. He became the 1986 winner of the Society for Neuroscience's Donald B. Lindsley Prize in Behavioral Neuroscience for his work. Later, he moved on to investigate visual, circadian, and serotonergic mechanisms of neuroplasticity. In addition, he helped find that constant light can desynchronize the circadian cells in the suprachiasmatic nucleus (SCN). He has always been interested in the underlying causes of behavior and examining the long term changes in behavior and physiology in the neurological modular system. McMahon helped identifying a retrograde neurotransmission system in the retina involving the melanopsin containing ganglion cells and the retinal dopaminergic amacrine neurons.

Frank Werblin is Professor of the Graduate School, Division of Neurobiology at the University of California, Berkeley.

Jean Bennett is the F. M. Kirby Professor of Ophthalmology in the Perelman School of Medicine at the University of Pennsylvania. Her research focuses on gene therapy for retinal diseases. Her laboratory developed the first FDA approved gene therapy for use in humans, which treats a rare form of blindness. She was elected a member of the National Academy of Sciences in 2022.

References

  1. 1 2 3 4 5 6 7 8 9 Vlasits, Anna (2016-09-01). "He may be the rightful inventor of neuroscience's biggest breakthrough in decades. But you've never heard of him". STAT. Retrieved 2018-12-15.
  2. 1 2 Grens, Kerry (2016-09-01). "The History of Optogenetics Revised". The Scientist Magazine. Retrieved 2018-12-15.
  3. "光遗传学创始人:浦江籍科学家潘卓华". Zhejiang Online. 2018-01-03. Retrieved 2018-12-15.
  4. "一定拿诺奖的光遗传学和被遗忘的潘卓华". University of Science and Technology of China Initiative Foundation. 2016-09-02. Retrieved 2018-12-15.
  5. 1 2 3 4 5 "Zhuo-Hua Pan". Wayne State University. Retrieved 2018-12-15.
  6. 1 2 Gallagher, John (2016-09-27). "WSU research leads to algae treatment for blindness". Detroit Free Press. Retrieved 2018-12-17.