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The lab focuses mainly on the biology of cell adhesion, particularly as it relates to establishing synaptic connections between neurons, using the retina as the primary model system. Research in the lab encompasses both molecular-level studies using X-ray crystallography to understand the structure and function of individual proteins, as well as cellular and histologic studies to understand their roles in vivo. There are two primary projects underway in our laboratory: (1) We are examining the structure, function, and retinal expression of a family of putative neural cell adhesion proteins called protocadherins. These proteins, which are distinct from yet resemble cadherin cell adhesion proteins, are expressed with a remarkable specificity: Neurons of identical lineage in close proximity to each other appear to choose one or a few protocadherins to express (of the 52 in the genome), and this choice differs from one cell to the next. Protocadherins are localized primarily at synapses, suggesting the possibility that their differential adhesion may be important in wiring neural circuits. To investigate this possibility, we have produced specific antibodies to 15 of the 52 protocadherins, and using immunohistochemistry are in the process of correlating the expression of these proteins with the known neural circuits of the retina. (2) We are also investigating the biology of tubby proteins, which we have shown to function as signaling factors downstream from heterotrimeric G-proteins. The tubby mutant mouse exhibits an obesity/insulin-resistance/retinopathy phenotype, and dysfunction of tubby-like protein 1(TULP1) is the cause of retinitis pigmentosa type 14. A collaborator in France has identified a human tubby mutants who exhibit a syndrome similar to that of the tubby mouse. We are now working to understand the biochemical origin of the dysfunction of these mutants.
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biorxiv(2024)
Nicholas C Morano, Davys S Lopez,Hagar Meltzer,Alina P Sergeeva,Phinikoula S Katsamba, Himanshu Pawankumar Gupta, Jordan E Becker,Bavat Bornstein,Filip Cosmanescu,Oren Schuldiner, Richard S Mann,Barry Honig,
biorxiv(2024)
S Zipursky, John Lee,Alina Sergeeva,Goran Ahlsen,Seetha Mannepalli,Fabiana Bahna,Kerry Goodman,Baljit Khakh, Joshua Weiner,Lawrence Shapiro,Barry Honig
Research square (2024)
bioRxiv : the preprint server for biology (2023)
PLoS pathogensno. 9 (2023): e1011584-e1011584
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Kartikeya Nagendra,Adrien Izzet, Nicolas Byron Judd,Ruben Zakine, Leah Friedman,Oliver J Harrison,Léa-Laetitia Pontani,Lawrence Shapiro,Barry Honig,Jasna Brujic
Biophysical journalno. 17 (2023): 3506-3515
Immunityno. 10 (2023): 2442-2455.e8
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Cell reportsno. 7 (2023): 112755-112755
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