Yuchen Wang, PhD, has joined the UAB School of Optometry as an assistant professor in research. Wang is fascinated by how neurons communicate with each other, and his long-term career goal is to understand how synapses in sensory systems, particularly visual systems, achieve and maintain fast and reliable signal transmission, which enables a seamless and accurate perception of our environment.
"The excellent research and academic environment, especially the outstanding vision science community at UAB are what excite me the most to join UABSO," Wang said. "Birmingham is the type of city that both me and my family would like to live in because of its great natural environment, reasonable cost of living and convenient domestic and international transportation."
Wang received his 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. He 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,” Wang said. “This study provides a molecular mechanism for the rational design of therapeutically valuable subtype-selective VGCC blockers.”
Previously, Wang was a postdoctoral fellow in neuroscience at the Scripps Research Institute in Florida, where he joined the lab of Kirill Martemyanov 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, Wang identified novel trans-synaptic mechanisms underlying the selective wiring of each type of photoreceptors.
Specifically, he 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,” Wang said. “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.”
Wang’s postdoc findings open an exciting avenue of exploring the general role of CAMs in orchestrating the complex process of synapse formation and function. His 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.