T
Timothy S. Fisher
Researcher at Merck & Co.
Publications - 17
Citations - 1275
Timothy S. Fisher is an academic researcher from Merck & Co.. The author has contributed to research in topics: LDL receptor & PCSK9. The author has an hindex of 14, co-authored 17 publications receiving 1217 citations. Previous affiliations of Timothy S. Fisher include Albert Einstein College of Medicine.
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Journal ArticleDOI
Cholesterol Efflux Potential and Antiinflammatory Properties of High-Density Lipoprotein After Treatment With Niacin or Anacetrapib
Laurent Yvan-Charvet,Jelena Kling,Tamara A. Pagler,Hongna Li,Brian K. Hubbard,Timothy S. Fisher,Carl P. Sparrow,Andrew K. P. Taggart,Alan R. Tall +8 more
TL;DR: Niacin treatment caused a moderate increase in the ability of HDL to promote net cholesterol efflux, whereas inhibition of cholesteryl ester transfer protein via anacetrapib led to a more dramatic increase in association with enhanced particle functionality at higher HDL concentrations.
Journal ArticleDOI
Effects of pH and Low Density Lipoprotein (LDL) on PCSK9-dependent LDL Receptor Regulation
Timothy S. Fisher,Paola Lo Surdo,Shilpa Pandit,Marco Mattu,Joseph C. Santoro,Douglas Wisniewski,Richard T. Cummings,Alessandra Calzetta,Rose M. Cubbon,Paul A. Fischer,Anil Tarachandani,Raffaele De Francesco,Samuel D. Wright,Carl P. Sparrow,Andrea Carfi,Ayesha Sitlani +15 more
TL;DR: The results of the biochemical and cell-based experiments suggest a model in which secreted PCSK9 binds to LDLR and directs the trafficking of LDLR to the lysosomes for degradation.
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Structural and Biochemical Characterization of the Wild Type PCSK9-EGF(AB) Complex and Natural Familial Hypercholesterolemia Mutants
Matthew J. Bottomley,Agostino Cirillo,Laura Orsatti,Lionello Ruggeri,Timothy S. Fisher,Joseph C. Santoro,Richard T. Cummings,Rose M. Cubbon,Paola Lo Surdo,Alessandra Calzetta,A. Noto,Jennifer Baysarowich,Marco Mattu,Fabio Talamo,Raffaele De Francesco,Carl P. Sparrow,Ayesha Sitlani,Andrea Carfi +17 more
TL;DR: It is found that although the EGF(AB)H306Y-PCSK9 interaction is pH-independent, LDLRH306Y binds PCSK 9 50-fold better at low pH, suggesting that factors other than His-306 contribute to the pH dependence of PCSK9-LDLR binding.
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A Proprotein Convertase Subtilisin-like/Kexin Type 9 (PCSK9) C-terminal Domain Antibody Antigen-binding Fragment Inhibits PCSK9 Internalization and Restores Low Density Lipoprotein Uptake
Yan G. Ni,Jon H. Condra,Laura Orsatti,Xun Shen,Stefania Di Marco,Shilpa Pandit,Matthew J. Bottomley,Lionello Ruggeri,Richard T. Cummings,Rose M. Cubbon,Joseph C. Santoro,Anka G. Ehrhardt,Dale Lewis,Timothy S. Fisher,Sookhee Ha,Leila Njimoluh,Dana D. Wood,Holly A. Hammond,Douglas Wisniewski,Cinzia Volpari,A. Noto,Paola Lo Surdo,Brian K. Hubbard,Andrea Carfi,Ayesha Sitlani +24 more
TL;DR: It is demonstrated that thePCSK9 C-terminal domain contribute to its inhibition of LDLR function mainly through its role in the cellular uptake of PCSK9 and LDLR complex.
Journal ArticleDOI
Biochemical characterization of cholesteryl ester transfer protein inhibitors
Mollie Ranalletta,Kathleen K. Bierilo,Ying Chen,Denise P. Milot,Qing Chen,Elaine Tung,Caroline Houde,Nadine Elowe,Margarita Garcia-Calvo,Gene Porter,Suzanne S. Eveland,Betsy Frantz-Wattley,Mike Kavana,George H. Addona,Peter J. Sinclair,Carl P. Sparrow,Edward A. O'Neill,Ken S. Koblan,Ayesha Sitlani,Brian K. Hubbard,Timothy S. Fisher +20 more
TL;DR: The biochemical characterization of anacetrapib, a potent inhibitor of CETP, was described and dalcetrapib was found to covalently label both human and mouse plasma proteins, indicating that these inhibitors promote the formation of a complex between CETP and HDL, resulting in inhibition of CETp activity.