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职业迁徙
个人简介
Research Focus
Chemical Biology and Biophysical Chemistry
A central focus of our research is to understand the principles of protein folding and to comprehend the basis for misfolding and/or aggregation diseases such that we can develop novel therapeutic strategies using chemistry, biophysical and biological approaches.
A multidisciplinary approach to understanding degenerative diseases linked to protein aggregation is a main focus of our laboratory. We concentrate on Alzheimer's disease, as well as the transthyretin- and light-chain-based amyloid diseases. Mechanistic studies of protein aggregation have led to small molecule and macromolecular amyloid fibril inhibition strategies, including the drug, tafamidis, discovered by the Kelly lab and sold by Pfizer. Our efforts to seek an aggregate structure-proteotoxicity relationship have led to insight into the etiology of these pathologies. Chemical synthesis of small molecule inhibitors designed to manipulate protein energetics is a significant component of our research program. We also use cell-based screens to discover mediators of the protein homeostasis network, including stress-responsive signaling pathway activators (in collaboration with the Wiseman lab) and autophagy activators, which should be generally useful to ameliorate amyloid diseases.
Investigation into lysosomal storage diseases are underway wherein small molecules that enhance the proteostasis network capacity of the secretory pathway and pharmacologic chaperones are being sought to correct genetic defects in the folding and trafficking of enzymes that are critical for lysosome function and therefore life.
All of the projects discussed thus far utilize bioorganic and biophysical chemistry approaches in combination with biological studies carried out in collaboration with several laboratories.
The Kelly lab in collaboration with the Wong lab discovered the enhanced aromatic sequon—sequences that are more efficiently N-glycosylated by cellls and which stabilize the native state of proteins that they are incoporated into as a consequence of aromatic side chain–N-glycan interactions. Using chemically synthesized WW domain analogs wherein we vary the aromatic side chain and the sugar, we are learning a great deal about the underpinnings of this stabilizing interaction.
Developing synthetic methodology to accomplish medicinal chemistry towards the development of drugs for several activators of proteostasis capacity is a central component of the lab. In addition, we use these methods to scrutinize the hypothesis that we can discover drugs via our Inverse Drug Discovery approach.
Chemical Biology and Biophysical Chemistry
A central focus of our research is to understand the principles of protein folding and to comprehend the basis for misfolding and/or aggregation diseases such that we can develop novel therapeutic strategies using chemistry, biophysical and biological approaches.
A multidisciplinary approach to understanding degenerative diseases linked to protein aggregation is a main focus of our laboratory. We concentrate on Alzheimer's disease, as well as the transthyretin- and light-chain-based amyloid diseases. Mechanistic studies of protein aggregation have led to small molecule and macromolecular amyloid fibril inhibition strategies, including the drug, tafamidis, discovered by the Kelly lab and sold by Pfizer. Our efforts to seek an aggregate structure-proteotoxicity relationship have led to insight into the etiology of these pathologies. Chemical synthesis of small molecule inhibitors designed to manipulate protein energetics is a significant component of our research program. We also use cell-based screens to discover mediators of the protein homeostasis network, including stress-responsive signaling pathway activators (in collaboration with the Wiseman lab) and autophagy activators, which should be generally useful to ameliorate amyloid diseases.
Investigation into lysosomal storage diseases are underway wherein small molecules that enhance the proteostasis network capacity of the secretory pathway and pharmacologic chaperones are being sought to correct genetic defects in the folding and trafficking of enzymes that are critical for lysosome function and therefore life.
All of the projects discussed thus far utilize bioorganic and biophysical chemistry approaches in combination with biological studies carried out in collaboration with several laboratories.
The Kelly lab in collaboration with the Wong lab discovered the enhanced aromatic sequon—sequences that are more efficiently N-glycosylated by cellls and which stabilize the native state of proteins that they are incoporated into as a consequence of aromatic side chain–N-glycan interactions. Using chemically synthesized WW domain analogs wherein we vary the aromatic side chain and the sugar, we are learning a great deal about the underpinnings of this stabilizing interaction.
Developing synthetic methodology to accomplish medicinal chemistry towards the development of drugs for several activators of proteostasis capacity is a central component of the lab. In addition, we use these methods to scrutinize the hypothesis that we can discover drugs via our Inverse Drug Discovery approach.
研究兴趣
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Mathew S. Maurer,Prem Soman,Adrian Hernandez,Pablo Garcia-Pavia, James Signorovitch, L. J. Wei,Mazen Hanna,Frederick L. Ruberg,Michelle Kittleson,Dhruv Kazi,Sharmila Dorbala,Kristen Hsu,
Advances in Therapypp.1-20, (2024)
Thierry Touvier,Francesca A. Veneri,Anke Claessens,Cinzia Ferri,Rosa Mastrangelo, Noémie Sorgiati,Francesca Bianchi, Serena Valenzano,Ubaldo Del Carro,Cristina Rivellini,Phu Duong,Michael E. Shy,
bioRxiv the preprint server for biology (2024)
Karla Cárdenas-Soto, Xel-Ha Dominguez, Giovanni Cortes,Felix Tsai, Maria Del Mar Saniger, Paola Guraieb-Chahin, Benjamín Torres-Ocatvo,Christopher Gibbons,Jeffery W Kelly,Roy Freeman,Alejandra González-Duarte
Journal of the peripheral nervous system : JPNS (2024)
Valerie Perea, Christian Cole,Justine Lebeau, Vivian Dolina,Kelsey R Baron,Aparajita Madhavan,Jeffery W. Kelly,Danielle Ann Grotjahn,Rockland Luke Wiseman
crossref(2023)
PROTEIN SCIENCEno. 12 (2023)
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bioRxiv (Cold Spring Harbor Laboratory)no. 15 (2023)
Leonard Yoon, Rachel C. Botham,Adriaan Verhelle, Yin Wu, Christian M. Cole,Ee Phie Tan, Lynée A. Massey,Pablo Sanz-Martinez, Ching-Chieh Chou,Jin Xu,Lisa P. Elia, Kyunga Lee,
biorxiv(2023)
Lina Xie,Marianne E Bowman,Gordon V Louie,Cheng Zhang,Maziar S Ardejani, Xuemei Huang,Qian Chu,Cynthia J Donaldson,Joan M Vaughan, Huanqi Shan,Evan T Powers,Jeffery W Kelly,
Biochemistryno. 21 (2023): 3050-3060
bioRxiv : the preprint server for biology (2023)
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