Yuchen Wang, PhD

Assistant Professor

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(205) 975-0734
VH 390C

Teaching/research interests: Physiology, anatomy, neurobiology and biochemistry of the retina

Office hours: By appointment

Education:

  • BS, China Pharmaceutical University, Biological Sciences
  • PhD, Purdue University, Molecular Pharmacology

Post-doctoral Training:

  • Postdoctoral Research Associate, The Scripps Research Institute, Neuroscience
  • Postdoctoral Fellow, The Scripps Research Institute, Neuroscience

I’m fascinated by how neurons communicate with each other and my long-term career goal is to understand how synapses in sensory systems, particularly visual system, achieve and maintain fast and reliable signal transmission which enables a seamless and accurate perception of our environment.

I received my PhD training under the supervision of Dr. Gregory Hockerman at Purdue University on the biophysics and molecular pharmacology of voltage-gated calcium channels (VGCCs) and Ca2+ signaling in pancreatic β cells. I identified a VGCC intrinsic mechanism that controls VGCC’s subcellular localization and demonstrated its importance for efficient Ca2+-dependent insulin secretion and its relevance to type 2 diabetes. I also dissected the molecular basis underlying the similar yet distinct pharmacological properties of two structurally similar VGCC subtypes. This study provides a molecular mechanism for the rational design of therapeutically valuable subtype-selective VGCC blockers.

I joined Dr. Kirill Martemyanov’s lab at Scripps Florida in 2015 to study the molecular mechanisms that govern the selective wiring of two types of photoreceptors: rods and cones, which are the primary light sensors in the retina. The selective synaptic connections of photoreceptors with their corresponding downstream ON-bipolar neurons is essential for vision and dysfunction of photoreceptor synapses causes retinal diseases including night blindness.

Using molecular, cellular, biochemical combined with mouse genetics and electrophysiology, I identified novel trans-synaptic mechanisms underlying the selective wiring of each type of photoreceptors. Specifically, I discovered that an auxiliary subunit of presynaptic VGCC, α2δ4, controls rod synapse formation and rod-mediated scotopic vision through regulating the membrane targeting and biophysical properties of VGCC, and in addition, through interacting with leucine-rich repeat-containing synaptic CAMs (LRR-CAM), ELFN1, which interacts trans-synaptically with and modulate the pharmacology of the post-synaptic glutamate receptor mGluR6. This work provides molecular insights into the etiology of night blindness as mutations in genes that encode α2δ4 protein were identified in night blind patients. As for cone photoreceptors, I have demonstrated that the functional wiring of cone photoreceptors is governed by an interplay of two LRR-CAMs, ELFN1 and ELFN2, both of which interact with mGluR6 trans-synaptically. I also discovered that LRIT1, another LRR-CAM, specifies the functional property of cone synapse and contributes to cone-mediated visual acuity partly through modulating the synaptic scaling and efficacy via interacting with presynaptic releasing machinery and postsynaptic mGluR6.

My postdoc findings open an exciting avenue of exploring the general role of CAMs in orchestrating the complex process of synapse formation and function. My independent research funded by National Eye Institute (NEI K99/R00) was designed to test the hypothesis that CAMs-mediated trans-synaptic adhesions and signaling perform multifarious roles in the formation, specification and plasticity of retinal synapses. This research will serve as a gateway to understand how synaptic adhesion and signaling encode and process different aspects of visual information and how retinal synaptic malfunction leads to visual deficits.

Teaching/Research Interest

The ability of the central nervous system (CNS) to process information depends on the precisely formed synaptic connections. Dysfunction of synapses have been strongly implicated in many neurological diseases. Given their functional significance, understanding how synapses are selectively assembled to form stereotyped neural circuits and how they are differentially tuned to the diverse functional demands of neural circuits is of central importance for both basic and translational neuroscience research.

Increasing studies have supported the hypothesis that synapse formation is controlled by various families of cell adhesion molecules (CAMs), which are cell-surface molecules critical for establishing cell-cell contacts and mediating subsequent intracellular signaling. Despite many studies, the precise role of each CAM in information processing, particularly how CAM-mediated synaptic adhesion and signaling contribute to the encoding and processing of different aspects of a natural stimulus remains largely unknown.

The mammalian retina is a neural structure composed of more than 60 distinct neurons each uniquely wired into circuits and contributing to visual information processing. As part of CNS, the retina is one of the best-understood neural circuits in terms of the cellular compositions, structural connectivity and functional relevance. In addition, the natural stimulus of the retina, light, can be precisely controlled spatially and temporally. Thus, retina serves as an excellent model to study the molecular basis of CNS information processing.

Research of the lab focuses on understanding the synaptic adhesions and signaling underlying information processing and how these synaptic mechanisms are perturbed under pathophysiological conditions. My lab uses complementary and multi-scale strategies, including cell/molecular biology, biochemistry, transcriptomics/proteomics, mouse genetics, CRISPR/Cas9 gene editing and electrophysiology to study how CAM-mediated synaptic adhesion and signaling orchestrate pre-synaptic releasing apparatus and post-synaptic signaling complexes to shape retinal synaptic specificity and diversity. To achieve this goal, my lab is striving to answer the following questions:

  • How does pre-synaptic releasing machinery contribute to synapse formation and function?
  • How precise alignment between pre- and post-synaptic components is achieved and maintained?
  • How do pathophysiological conditions (such as degeneration and aging) affect synapses and whether the progression of these conditions could be slowed down or even reverted by restoring synaptic connection and function?

Publications

Yuchen Wang, Yan Cao, Cassandra Hays, Thibaut Laboute, Tom Ray, Debbie Guerrero-Given, Abhimanyu Ahuja, Dipak Patil, Olga Rivero Martín, Naomi Kamasawa, Jeremy Kay, Wallace Thoreson, Kirill Martemyanov. Adhesion GPCR Latrophilin3 regulates synaptic function of cone photoreceptors in a trans-synaptic manner. (2021). Proceedings of the National Academy of Sciences of the United States of America 118 (45) e2106694118

Yan Cao, Yuchen Wang, Henry Dunn, Cesare Orlandi, Naomi Kamasawa, David Fitzpatrick, Wei Li, Christina Zeits, William Hauswirth, Kirill A. Martemyanov. Interplay between cell adhesion molecules governs synaptic wiring of cone photoreceptors. (2020). Proceedings of the National Academy of Sciences of the United States of America 117(38):23914-23924

Lei Xu, Susan Bolch, Clayton P. Santiago, Frank Dyka, Omar Akil, Ekaterina Lobanova, Yuchen Wang, Kirill Martemyanov, William W. Hauswirth, W. Clay Smith, James T. Handa, Seth Blackshaw, John D. Ash, Astra Dinculescu (2019). Clarin-1 Expression in Adult Mouse and Human Retina Highlights a Role of Müller Glia in Usher Syndrome. Journal of Pathology 250(2):195-204

Tatsuo Itakura, Andrew Webster, Shravan K. Chintala, Nitin Patel, Yuchen Wang, Jose M. Gonzalez, Jr., James C.H. Tan, Janice A. Vranka, Ted Acott, Cheryl M. Craft, Maria E. Sibug Saber, Shinwu Jeong, W. Daniel Stamer, Kirill A. Martemyanov, M. Elizabeth Fini (2019). Homeostatic Role for GPR158 in Regulation of Intraocular Pressure. Journal of Ocular Pharmacology and Therapeutics 35(4):203-215

Cesare Orlandi, Yoshihiro Omori, Yuchen Wang, Akiko Ueno, Michael J Roux, Giuseppe Condomitti, Joris de Wit, Takahisa Furukawa and Kirill A. Martemyanov (2018). Trans-synaptic Interaction of Orphan Receptor GPR179 with Dystroglycan-Pikachurin Complex Is Essential for the Synaptic Organization of Photoreceptors. Cell Reports 25(1): 130-145.e5

Yuchen Wang*, Shiqi Tang*, Kyle E. Harvey, T. August Li, Amy E. Salyer, Gregory H. Hockerman (2018). Molecular determinants of the differential modulation of Cav1.2 and Cav1.3 by nifedipine and FPL64176. Molecular Pharmacology 94(3):973-983 (*contribute equally to the work)

Ignacio Sarria*, Yan Cao*, Yuchen Wang*, Norianne T. Ingram, Cesare Orlandi, Naomi Kamasawa, Alexander V. Kolesnikov, Vladimir J. Kefalov, Alapakkam P. Sampath, Kirill A. Martemyanov (2018). LRIT1 modulates adaptive changes in synaptic communication of cone photoreceptors. Cell Reports 22: 3562–3573 (* contribute equally to the work)

Yuchen Wang, Katherine Fehlhaber, Ignacio Sarria, Yan Cao, Alapakkam P. Sampath, Kirill A. Martemyanov (2017). Auxiliary calcium channel subunit α2δ4 is selectively required for axonal elaboration, synaptic transmission and wiring of rod photoreceptors (2017). Neuron 93: 1359-1374 (Previewed: Aligning a Synapse, Daniel Kerschensteiner (2017), Neuron 93: 1241-1243)

Yuchen Wang, Rachel E. Jarrard, Evan P.S. Pratt, Marcy L. Guerra, Amy E Salyer, Allison M. Lange, Ian M. Soderling, and Gregory H. Hockerman (2014). Uncoupling of Cav1.2 from Ca2+-induced Ca2+ Release and SK channel Regulation in Pancreatic β-cells. Molecular Endocrinology 28: 458-476

Rachel E. Jarrard, Yuchen Wang, Amy E. Salyer, Evan P. Pratt, Ian M. Soderling, Marcy L. Guerra, Allison M. Lange, Hillary J. Broderick and Greg H. Hockerman (2013). Potentiation of Sulfonylurea Action by an EPAC-selective cAMP Analog in INS-1 Cells: Comparison of Tolbutamide and Gliclazide, and a Potential Role for EPAC Activation of a 2-APB-sensitive Ca2+ Influx. Moleluclar Pharmacology 83: 191-205

Xuri Wu, Yuchen Wang, Jianming Ju, Chen Chen, Nan Liu and Yijun Chen (2009). Enantioselective Synthesis of Ethyl S-2-hydroxy-4-phenylbutyrate by Recombinant Diketoreductase. Tetrahedron Asymmetry 20, 2504-2509

 

Honors & Awards

November 2020 - Best presentation award, Scripps Research Fest Scientific Symposium

September 2019 - NIH Pathway to Independence Award (K99/R00), NIH/NEI

2017-2018 - Best poster awards, Scripps Research Fest Scientific Symposium

June 2017 - Travel award, FASEB-The Biology and Chemistry of Vision Conference

June 2017 - Best poster award, FASEB-The Biology and Chemistry of Vision Conference

July 2016 - Travel award, FASEB-Retinal Neurobiology and Visual Processing Conference

2015 - Koo Travel Award, the Department of Medicinal Chemistry and Molecular Pharmacology, Purdue

2015 - Travel Award, ASPET Annual Meeting at Experimental Biology

2014 - Best Poster Award, Sigma Xi Life Science Competition, Purdue

2006-2009 - University Scholarship for outstanding academic performance, China Pharmaceutical University