Draft:Samuel Miao-Sin Wu


Dr. Wu prepared a living retinal slice for electrophysiological recording

Samuel Miao-Sin Wu (Chinese: 吳淼鑫; born July 7, 1948) is a Chinese-born American neuroscientist and Professor of Ophthalmology, Neuroscience, Molecular Physiology and Biophysics, and the Camille and Raymond Hankamer Chair in Ophthalmology at Baylor College of Medicine in Houston, Texas, United States.

Early life and Education

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Wu was born in Beijing, China, and attended the Da-Shui-Che Hutong Elementary School and one year at the 41st Middle School before moving to Hong Kong with his family in 1962. In Hong Kong, he spent the first year catching up Cantonese and English, then attended Pui-Ching Middle School and graduated in 1969. He then went to the United States for higher education, where he graduated with an A.B. in Physics and Biophysics from University of California, Berkeley in 1973, with distinction in general scholarship and honors program completed in Biophysics with distinction. He went on to pursue a Ph.D. in Biophysics at Harvard University, which he completed in 1979 under the mentorship of Professor John E. Dowling, a paramount leader in retinal research. His Ph.D. research laid the foundation for his lifelong interest in neuroscience and retinal physiology. After receiving Ph.D., Wu conducted postdoctoral research in neurobiology at University of California, Berkeley (1979–1982), where he worked in the laboratory of Professor Frank Werblin, a prominent neuroscientist in the field of visual information processing.

Academic Career

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In 1982, Wu began his career at Baylor College of Medicine in Houston, Texas, as an Assistant Professor of Ophthalmology, Physiology, and Molecular Biophysics. He was promoted to Associate Professor in 1988 and to full Professor in 1993, and since 2002 he has been appointed as the Camille and Raymond Hankamer Chair in Ophthalmology at Baylor College of Medicine. He is also the Director of the Vision Research Training Program and the Principal Investigator of the Core Grant for Vision Research of Baylor College of Medicine. In addition to his roles at Baylor, Wu has extended his academic influence on other institutions. He has been an Adjunct Professor in the Department of Physics at University of Houston since 2003 and in the Department of Bioengineering at Rice University from 2009 to 2015. In the educational arena, he taught a course in cellular neurophysiology for over 20 years at Baylor and Rice University, as well as several times at Ut Austin and in Hong Kong, and published a textbook (with Daniel Johnston) "Foundations of Cellular Neurophysiology" (the MIT Press, 1995). He also taught a course "Physiology of the Visual System" at Baylor and Hong Kong Polytechnic University and co-edited several vision research volumes. During the past years, he has mentored 12 PhD or MD/PhD students and 17 postdoctoral fellows and served as a member of PhD thesis committees of over 40 graduate students from other labs.

Research Interests and Contributions

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Wu's research primarily focuses on the molecular and synaptic mechanisms underlying retinal function and dysfunction. His work has been pivotal in understanding how visual signals are processed by the Retina, particularly through Rod photoreceptor and Cone photoreceptor interactions and parallel information pathways mediating ON/OFF, rod/cone and center/surround signals in the retina. Wu and his lab have discovered key roles played by ion channels (such as HCN channel and Gap junction), neurotransmitter receptors (such as AMPA/KA/mGluR6 glutamate and GABA/glycine receptors) and synaptic circuits (such as the AIIAC circuits) in visual processing in normal and diseased retinas. They found, for example, that rod and cone bipolar cells use different neurotransmitter receptors in synapses mediating their receptive fields and thus the retina processes spatial information via different synaptic mechanisms under different lighting conditions. They also discovered that rod and cone inputs to different types of Retinal ganglion cell (RGCs) are mediated via different synaptic circuits and thus RGCs are differentially vulnerable to pathological insults and disease treatment and prevention should be designed accordingly.   Wu's work has greatly advanced our understanding of signal computation and structural and functional organization of the visual system in healthy and diseased states. His lab has also pioneered studies on how gene products mediate retinal function and how disruption in these products leads to eye diseases such as retinitis pigmentosa, Glaucoma, and Bardet–Biedl syndrome. Wu is among the first who push forward the concept that physiological changes occur prior to irreversible structural changes in diseases (such as RGC damage in glaucoma) and remedies/treatments at stages of physiological changes are more efficient than when structural damage occurs. In recent years, Wu's group developed a multiple patch electrode recording technique that allow for the first time simultaneous patch clamp recordings from up to 8 retinal cells. They used this technique to unravel how electrical coupling and HCN channel shape the outputs of the two-dimensional photoreceptor network, a task unattainable with single or double electrodes. Moreover, this technique enables Wu's group to determine the contribution of specific neurons in intermediate positions of synaptic circuits, such as bipolar cells in the photoreceptor-bipolar-ganglion cell pathways, by comparing voltage responses of the ganglion cells before and after the bipolar cells are voltage clamped, as voltage signals from photoreceptors to ganglion cells are blocked at the bipolar cell level when they are voltage clamped. This "voltage clamp block" technique not only helps to dissect synaptic connectivity in the retina, but also provides a new tool for functional analysis of neural circuits in the entire brain.

Awards and Honors

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1973, Honor A.B. degree in Biophysics with distinction (U.C. Berkeley).

1971-1973, General Scholarship (U.C. Berkeley).

1973-1976, Harvard Grant-in-Aid Fellowship.

1979-1982, National Research Service Award, NIH.

1987, Sam and Bertha Brochstein Award for Outstanding Achievement in Retina Research, Retina Research Foundation.

1989, Dolly Green Scholars Award, Research to Prevent Blindness, Inc.

1991, Marjorie W. Margolin Prize, Retina Research Foundation.

1997, Senior Scientific Investigators Award, Research to Prevent Blindness, Inc.

1998, James M. Barr Award for Outstanding Retina Research in the Greater Houston Area, Retina Research Foundation.

2005, James M. Barr Award for Outstanding Retina Research Achievement, Retina Research Foundation.

2006, Boycott Prize, FASEB Summer Research Conference "Retinal Neurobiology and Visual Processing".

2008, Ludwig von Sallmann Prize, International Society for Eye Research.

2009, Friedenwald Award, Association for Research in Vision and Ophthalmology.

2011, Alcon Research Institute Award, 2011.

2017, BRASS Mentor of the Year Award, Baylor Research Advocates for Student Scientists.

2020, Retina Research Foundation Paul Kayser International Award in Retina Research, International Society for Eye Research.

National Scientific Participation and Service

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National Institutes of Health study sections: VISA-1 (1990); VISA-2 (1991); VISC (1992-1994, 1997, 2001); NINDS Program Project Review Committee (1997); NEI Special Emphasis Panels (ZEY1VSN:1996-2013; ZEY1VSN02: 2014; ZEY1VSN03: 2014, 2016, 2021; ZEY1VSN04: 2022; R03: 2001–2004); BDPE: 2007,2011; NTRC: 2014-2020.

Program Planning Committee, Association for Research in Vision and Ophthalmology: 1993-1995 (Chair 1995).

Editorial Responsibilities

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Vision Research: Section Editor, Neurobiology Section: 1992-2003.

Experimental Eye Research: Editor: 1993-1999.

Journal of Physiology: Review Editor: 2012-2015

Ad-Hoc Reviewers: Brain Research, Journal of Neurophysiology, Journal of Neuroscience, Journal of Neuroscience Methods, Journal of Physiology, Visual Neuroscience, Investigative of Ophthalmology and Visual Sciences, Proceedings of the National Academy of Sciences, Neuron.

Selected publications

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1.        Attwell, D., Wilson, M. and Wu, S. M. (1984).  A quantitative analysis of interactions between photoreceptors in the salamander (Ambystoma) retina[1].  J. Physiol. 352:703-737. PMID: 6747904.

2.        Attwell, D., Borges, S., Wu, S.M., and Wilson, M. (1987).  Signal clipping by the rod output synapse.[2]  Nature, 328:522-524. PMID: 3039370.

3.        Yang, X. L. and Wu, S. M. (1989).  Modulation of rod-cone coupling by light.[3]  Science, 244, 352-354. PMID: 2711185.

4.        Wu, S.M. (1991).  Input-output relations of the feedback synapse between horizontal cells and cones in the tiger salamander retina[4].  J. Neurophysiol, 65, 1197-1206. PMID: 1651374.

5.        Johnston, D. and Wu, S.M. (1995).  Foundations of Cellular Neurophysiology.[5] The MIT Press.

6.        Wu, S.M., Gao, F. and Maple, B.R. (2000) Functional architecture of synapses in the inner retina: segregation of visual signals by stratification of bipolar cell axon terminals.[6] J. Neuroscience, 20, 12, 4462-4470. PMID: 19844015.

7.        Pang, J. J., Gao, F. and Wu, S. M. (2003) Light-evoked excitatory and inhibitory synaptic inputs to ON and OFF α ganglion cells in the mouse retina.[7] J. Neuroscience 23, 14, 6063-6073. PMID: 12853425.

8.        Pennesi, M.E., Howes, K.A., Baehr, W., and Wu, S.M. (2003) GCAP1 rescues cone                                 photoreceptor responses in GCAP1/GCAP2 knockout mice.[8] Proc. Nat. Acad. Scien. (USA) 100, 11, 6783-6788. PMID: 12732716.

9.        Zhang, A.J. and Wu, S.M. (2009) Receptive fields of retinal bipolar cells are mediated by heterogeneous synaptic circuitry.[9] J. Neuroscience, 29 (3), 789-797. PMID: 24000179.

10.  Barrow, A. and Wu, S.M. (2009) Low conductance HCN1 channels augment the frequency response of rod and cone photoreceptors.[10] J. Neuroscience.  29, 5841-5853. PMID: 19420251.

11.  Pang, J.J., Gao, F., Lem, J., Bramblett, D.E., Paul, D.L. and Wu, S.M. (2010) Direct rod input to cone BCs and direct cone input to rod BCs challenge the traditional view of mammalian BC circuitry.[11] Proc. Nat. Acad. Scien. (USA), 107, 1, 395-400. PMID: 20018684.

12.  Simons D. L., Boye, S. L., Hauswirth, W. W. and Wu, S. M. (2011) Gene therapy prevents photoreceptor death and preserves retinal function in a Bardet-Biedl Syndrome mouse model.[12]  Proc. Nat. Acad. Scien. (USA), 108(15):6276-81. PMID: 21444805.

13.  Pang, J.J., Frankfort, B.J., Gross, R.L. and Wu, S.M. (2015) Elevated intraocular pressure decreases response sensitivity of inner retinal neurons in experimental glaucoma mice.[13] Proc. Nat. Acad. Scien. (USA), 112, 8, 2593-2598. PMID: 25675503.

14.  Sabharwal, J., Seilheimer, R. L.,  Tao, X, Cowan, C.S., Frankfort, B. J. and Wu, S.M. (2017)  Elevated IOP alters the space–time profiles in the center and surround of both ON and OFF RGCs  in mouse.[14] Proc. Nat. Acad. Scien. (USA), August 15, 114, 33, 8859-8864. PMID: 28760976.

15.  Pang J.J., Jiang, XL and Wu, S.M. (2024) Linear and nonlinear behaviors of the photoreceptor coupled network.[15] J. Neuroscience, 44 (16), 1433-1443. PMID: 38423760.

References

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  1. ^ Attwell, D; Wilson, M; Wu, S M (July 3, 1984). "A quantitative analysis of interactions between photoreceptors in the salamander (Ambystoma) retina". The Journal of Physiology. 352 (1): 703–737. doi:10.1113/jphysiol.1984.sp015318. PMC 1193238. PMID 6747904.
  2. ^ Attwell, David; Borges, Salvador; Wu, Samuel M.; Wilson, Martin (August 3, 1987). "Signal clipping by the rod output synapse". Nature. 328 (6130): 522–524. Bibcode:1987Natur.328..522A. doi:10.1038/328522a0. PMID 3039370 – via www.nature.com.
  3. ^ Yang, Xiong-Li; Wu, Samuel M. (April 21, 1989). "Modulation of Rod-Cone Coupling by Light". Science. 244 (4902): 352–354. Bibcode:1989Sci...244..352Y. doi:10.1126/science.2711185. PMID 2711185 – via CrossRef.
  4. ^ Wu, S. M. (1991). "Input-output relations of the feedback synapse between horizontal cells and cones in the tiger salamander retina". Journal of Neurophysiology. 65 (5): 1197–1206. doi:10.1152/jn.1991.65.5.1197. PMID 1651374.
  5. ^ "Foundations of Cellular Neurophysiology". MIT Press.
  6. ^ Wu, Samuel M.; Gao, Fan; Maple, Bruce R. (June 15, 2000). "Functional Architecture of Synapses in the Inner Retina: Segregation of Visual Signals by Stratification of Bipolar Cell Axon Terminals". Journal of Neuroscience. 20 (12): 4462–4470. doi:10.1523/JNEUROSCI.20-12-04462.2000. PMC 6772452. PMID 10844015 – via www.jneurosci.org.
  7. ^ Pang, Ji-Jie; Gao, Fan; Wu, Samuel M. (July 9, 2003). "Light-Evoked Excitatory and Inhibitory Synaptic Inputs to ON and OFF α Ganglion Cells in the Mouse Retina". Journal of Neuroscience. 23 (14): 6063–6073. doi:10.1523/JNEUROSCI.23-14-06063.2003. PMC 6740343. PMID 12853425 – via www.jneurosci.org.
  8. ^ Pennesi, M. E.; Howes, K. A.; Baehr, W.; Wu, S. M. (2003). "Guanylate cyclase-activating protein (GCAP) 1 rescues cone recovery kinetics in GCAP1/GCAP2 knockout mice | PNAS". Proceedings of the National Academy of Sciences of the United States of America. 100 (11): 6783–6788. doi:10.1073/pnas.1130102100. PMC 164524. PMID 12732716.
  9. ^ Zhang, Ai-Jun; Wu, Samuel M. (January 21, 2009). "Receptive Fields of Retinal Bipolar Cells Are Mediated by Heterogeneous Synaptic Circuitry". Journal of Neuroscience. 29 (3): 789–797. doi:10.1523/JNEUROSCI.4984-08.2009. PMC 2745915. PMID 19158304 – via www.jneurosci.org.
  10. ^ Barrow, Andrew J.; Wu, Samuel M. (May 6, 2009). "Low-Conductance HCN1 Ion Channels Augment the Frequency Response of Rod and Cone Photoreceptors". Journal of Neuroscience. 29 (18): 5841–5853. doi:10.1523/JNEUROSCI.5746-08.2009. PMC 2695939. PMID 19420251 – via www.jneurosci.org.
  11. ^ Pang, Ji-Jie; Gao, Fan; Lem, Janis; Bramblett, Debra E.; Paul, David L.; Wu, Samuel M. (January 5, 2010). "Direct rod input to cone BCs and direct cone input to rod BCs challenge the traditional view of mammalian BC circuitry". Proceedings of the National Academy of Sciences. 107 (1): 395–400. Bibcode:2010PNAS..107..395P. doi:10.1073/pnas.0907178107. PMC 2806755. PMID 20018684.
  12. ^ Simons, David L.; Boye, Sanford L.; Hauswirth, William W.; Wu, Samuel M. (April 12, 2011). "Gene therapy prevents photoreceptor death and preserves retinal function in a Bardet-Biedl syndrome mouse model". Proceedings of the National Academy of Sciences. 108 (15): 6276–6281. Bibcode:2011PNAS..108.6276S. doi:10.1073/pnas.1019222108. PMC 3076852. PMID 21444805.
  13. ^ Pang, Ji-Jie; Frankfort, Benjamin J.; Gross, Ronald L.; Wu, Samuel M. (February 24, 2015). "Elevated intraocular pressure decreases response sensitivity of inner retinal neurons in experimental glaucoma mice". Proceedings of the National Academy of Sciences. 112 (8): 2593–2598. Bibcode:2015PNAS..112.2593P. doi:10.1073/pnas.1419921112. PMC 4345598. PMID 25675503.
  14. ^ Sabharwal, J.; Seilheimer, R. L.; Tao, X.; Cowan, C. S.; Frankfort, B. J.; Wu, S. M. (August 15, 2017). "Elevated IOP alters the space–time profiles in the center and surround of both ON and OFF RGCs in mouse". Proceedings of the National Academy of Sciences. 114 (33): 8859–8864. Bibcode:2017PNAS..114.8859S. doi:10.1073/pnas.1706994114. PMC 5565456. PMID 28760976.
  15. ^ Pang, Ji-Jie; Jiang, Xiaolong; Wu, Samuel M. (April 17, 2024). "Linear and Nonlinear Behaviors of the Photoreceptor Coupled Network". Journal of Neuroscience. 44 (16): e1433232024. doi:10.1523/JNEUROSCI.1433-23.2024. PMC 11026348. PMID 38423760 – via www.jneurosci.org.