Michael D. Tomasini
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View article: Specific degrader for fusion oncokinase kills tumors and is augmented by bimodal degrader-siRNA
Specific degrader for fusion oncokinase kills tumors and is augmented by bimodal degrader-siRNA Open
Oncogenic fusions of two native proteins are challenging to block without disturbing the parental proteins. A mRNA delivered peptide degrader, selectively eliminates the oncogenic fusions DNAJB1::PRKACA and ATP1B1::PRKACA in fibrolamellar …
View article: Disruption of proteome by an oncogenic fusion kinase alters metabolism in fibrolamellar hepatocellular carcinoma
Disruption of proteome by an oncogenic fusion kinase alters metabolism in fibrolamellar hepatocellular carcinoma Open
Fibrolamellar hepatocellular carcinoma (FLC) is a usually lethal primary liver cancer driven by a somatic dysregulation of protein kinase A. We show that the proteome of FLC tumors is distinct from that of adjacent nontransformed tissue. T…
View article: Structures of the PKA RIα Holoenzyme with the FLHCC Driver J-PKAcα or Wild-Type PKAcα
Structures of the PKA RIα Holoenzyme with the FLHCC Driver J-PKAcα or Wild-Type PKAcα Open
View article: Structures of the PKA RIα holoenzyme with the FLHCC driver J-PKAcα or wild type PKAcα
Structures of the PKA RIα holoenzyme with the FLHCC driver J-PKAcα or wild type PKAcα Open
Fibrolamellar hepatocellular carcinoma (FLHCC) is driven by J-PKAcα, a kinase fusion chimera of the J-domain of DnaJB1 with PKAcα, the catalytic subunit of Protein Kinase A (PKA). Here we report the crystal structures of the chimeric fusio…
View article: Modeling the dynamics and kinetics of HIV-1 Gag during viral assembly
Modeling the dynamics and kinetics of HIV-1 Gag during viral assembly Open
We report a computational model for the assembly of HIV-1 Gag into immature viral particles at the plasma membrane. To reproduce experimental structural and kinetic properties of assembly, a process occurring on the order of minutes, a coa…
View article: Conformational Landscape of the PRKACA-DNAJB1 Chimeric Kinase, the Driver for Fibrolamellar Hepatocellular Carcinoma
Conformational Landscape of the PRKACA-DNAJB1 Chimeric Kinase, the Driver for Fibrolamellar Hepatocellular Carcinoma Open
In fibrolamellar hepatocellular carcinoma a single genetic deletion results in the fusion of the first exon of the heat shock protein 40, DNAJB1 , which encodes the J domain, with exons 2–10 of the catalytic subunit of protein kinase A, PR…
View article: A coarse-grained computational model of the nuclear pore complex predicts Phe-Gly nucleoporin dynamics
A coarse-grained computational model of the nuclear pore complex predicts Phe-Gly nucleoporin dynamics Open
The phenylalanine-glycine–repeat nucleoporins (FG-Nups), which occupy the lumen of the nuclear pore complex (NPC), are critical for transport between the nucleus and cytosol. Although NPCs differ in composition across species, they are lar…
View article: Carbohydrate-Derived Amphiphilic Macromolecules: A Biophysical Structural Characterization and Analysis of Binding Behaviors to Model Membranes
Carbohydrate-Derived Amphiphilic Macromolecules: A Biophysical Structural Characterization and Analysis of Binding Behaviors to Model Membranes Open
The design and synthesis of enhanced membrane-intercalating biomaterials for drug delivery or vascular membrane targeting is currently challenged by the lack of screening and prediction tools. The present work demonstrates the generation o…