Noga Vardi, Ph.D

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Adjunct Professor of Neuroscience
Department: Neuroscience

Contact information
131 Morgan Bldg
Department of Neuroscience
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA 19104-6058
Office: 6103579791
B.Sc (Biology)
Hebrew University, Jerusalem, 1974.
(Courses toward M.A in Neuroscience)
Hebrew University, Jerusalem, 1975.
Ph.D. (Maj. Neurobiology and Behavior, Min. Elec. Eng)
Cornell University, 1981.
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Description of Research Expertise

Retinal processing with focus on chemical architecture and principles of signal processing. Recently- Alzheimer

Electrophysiology; immunocytochemistry; electroretinogram; dye injection; electron microscopy; molecular biology; yeast two hybrid systems; computer simulation; live two photon imaging.

General Description: The retina provides an excellent model system for signal processing because the input (visual image) is well defined, the output (ganglion cell responses) has been thoroughly studied, and circuits of parallel pathways from photoreceptor to ganglion cells were described better than any other neural system. To reliably transfer the signal from photoreceptor to ganglion cells through these pathways under a large range of luminances the retina employs gain control and noise removal mechanisms. Gain is adjusted by GABAergic and glycinergic feedback circuits in the outer and inner plexiform layers. These circuits tune photoreceptor, bipolar and ganglion cells' responses by averaging and feeding back ambient light information. A major focus of the lab was the pathway of the ON bipolar cells and their signaling cascade. The ON bipolar cells express the metabotropic glutamate receptor mGluR6. This receptor activates Go, and this eventually closes the nonspecific TRPM1 cation channel. We studied the events that occur downstream of Go and how they are modulated. Whether Go activates directly the channel, or through a second messenger is important because the manner of activation determines the gain and the adaptation of these cells. In particular, both mGluR6 and Go are present in both rod and cone bipolar cells, but the two classes have different function (slow for night vision vs. fast for day vision), and one expects the cascade to differ in order to match and optimize the function. Another aspect of our studies is to figure out how the whole complex of the cascade is trafficked to the dendritic tip, and how a lack of a certain element destabilizes the complex and the synapse. Knowledge of this cascade is essential for understanding and treating night blindness. Another project concerns cone bipolar cell types; there exist about 5 types that are thought to conduct different temporal bandwidth. Nothing is known about their precise light properties and how they achieve their differences. We study this by calcium imaging of ON bipolar cells. Such understanding will shed light on day light vision and retinal diseases. I am recently engaged in applying the knowledge we acquired to therapeutic methods for structural and functional protection of retinal circuits. Furthermore, in collaboration with a biochemist who studies mitochondria function and dysfunction, I am researching new approaches to mitigate Alzheimer and Parkinson disease progression. The key in these studies is using small molecules (such as VBIT) that interfere with the mitochondrial processes that leads to cell death. Specifically, when the mitochondria senses abnormal changes, the channel VDAC1, which is important in transferring metabolites in and out of the mitochondria, get oligomerized and creates a large channel that allows cytochrome C to leave the mitochondria and activate caspases that then kill the cells. The VBIT molecules prevent the formation of the large channel.

Selected Publications

Verma A, Shteinfer-Kuzmine A, Kamenetsky N, Pittala S, Paul A, Nahon Crystal E, Ouro A, Chalifa-Caspi V, Pandey SK, Monsonego A, Vardi N, Knafo S, Shoshan-Barmatz V: Targeting the overexpressed mitochondrial protein VDAC1 in a mouse model of Alzheimer's disease protects against mitochondrial dysfunction and mitigates brain pathology. Transl Neurodegener 11(1): 58, 2022.

Feng Liu, Xiaobin Liu, Yamin Zhou, Yankun Yu, Ke Wang, Zhengqun Zhou, Hao Gao, Kwok-Fai So, Noga Vardi, Ying Xum: Wolfberry-derived zeaxanthin dipalmitate delays retinal degeneration in a mouse model of retinitis pigmentosa through modulating STAT3, CCL2 and MAPK pathways. JNC 158: 1131-1150, Sept. 2021.

Fina ME, Wang J, Nikonov SS, Sterling S, Vardi N, Kashina A, Dong DW.: Arginyltransferase (Ate1) regulates the RGS7 protein level and the sensitivity of light-evoked ON bipolar responses Sci. Rep. 11(1): 9376, Apr 2021.

Xu Y, Orlandi C, Cao Y, Yang S, Choi CI, Pagadala V, Birnbaumer L, Martemyanov KA, Vardi N.: The TRPM1 channel in ON-bipolar cells is gated by both the α and the βγ subunits of the G-protein Go. Scientific Reports 17;6:20940., 2016.

Tummala SR, Dhingra A, Fina ME, Li JJ, Ramakrishnan H, Vardi N. : Lack of mGluR6-Related Cascade Elements leads to Retrograde Trans-synaptic Effects on Rod Photoreceptor Synapses via Matrix-associated Proteins. Eur J Neurosci. 43(11): 1509-22, June 2016.

Ramakrishnan Hariharasubramanian, Dhingra Anuradha, Tummala Shanti R, Fina Marie E, Li Jian J, Lyubarsky Arkady, Vardi Noga: Differential Function of Gγ13 in Rod Bipolar and ON Cone Bipolar Cells. The Journal of physiology 593(7): 1531-50, Nov 2014.

Dhingra A, Tummala SR, Lyubarsky L, and Vardi N: PDE9A is expressed in the inner retina and contributes to the normal shape of the photopic ERG waveform. Frontiers in Molecular Neuroscience 7: 60, June 2014.

Nikonov Sergei S, Lyubarsky Arkady, Fina Marie E, Nikonova Elena S, Sengupta Abhishek, Chinniah Chidambaram, Ding Xi-Qin, Smith Robert G, Pugh Edward N, Vardi Noga, Dhingra Anuradha: Cones respond to light in the absence of transducin β subunit. The Journal of neuroscience : the official journal of the Society for Neuroscience 33(12): 5182-94, Mar 2013.

Dhingra Anuradha, Ramakrishnan Hariharasubramanian, Neinstein Adam, Fina Marie E, Xu Ying, Li Jian, Chung Daniel C, Lyubarsky Arkady, Vardi Noga: Gβ3 is required for normal light ON responses and synaptic maintenance. The Journal of neuroscience : the official journal of the Society for Neuroscience 32(33): 11343-55, Aug 2012.

Xu Y, Dhingra A, Fina ME, Koike C, Furukawa T, Vardi N.: mGluR6 deletion renders the TRPM1 channel in retina inactive. J Neurophysiol. 107(3): 948-57, Feb 2012.

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Last updated: 07/26/2023
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