Patrick M . McLendon

Learn More
The intermediate filament protein desmin is an integral component of the cardiomyocyte and serves to maintain the overall structure and cytoskeletal organization within striated muscle cells. Desmin-related myopathy can be caused by mutations in desmin or associated proteins, which leads to intracellular accumulation of misfolded protein and production of(More)
Basal autophagy is a crucial mechanism in cellular homeostasis, underlying both normal cellular recycling and the clearance of damaged or misfolded proteins, organelles and aggregates. We showed here that enhanced levels of autophagy induced by either autophagic gene overexpression or voluntary exercise ameliorated desmin-related cardiomyopathy (DRC). To(More)
Proteinopathy causes cardiac disease, remodeling, and heart failure but the pathological mechanisms remain obscure. Mutated αB-crystallin (CryAB(R120G)), when expressed only in cardiomyocytes in transgenic (TG) mice, causes desmin-related cardiomyopathy, a protein conformational disorder. The disease is characterized by the accumulation of toxic misfolded(More)
RATIONALE SUMOylation plays an important role in cardiac function and can be protective against cardiac stress. Recent studies show that SUMOylation is an integral part of the ubiquitin proteasome system, and expression of the small ubiquitin-like modifier (SUMO) E2 enzyme UBC9 improves cardiac protein quality control. However, the precise role of(More)
A versatile polycation scaffold that can easily be modified with targeting ligands has been designed, synthesized, and characterized. A series of galactose-containing polymers has been produced to demonstrate the ease of modification of this polynucleotide delivery vehicle motif via the click reaction and to study how various structural modifications affect(More)
The use of synthetic polymers for the delivery of nucleic acids holds considerable promise for understanding and treating disease at the molecular level. This work aims to decipher the cellular internalization mechanisms for a series of synthetic glycopolymer DNA delivery vehicles we have termed poly(glycoamidoamine)s (PGAAs). To this end, we have performed(More)
The delivery of nucleic acids with polycations offers tremendous potential for developing highly specific treatments for various therapeutic targets. Although materials have been developed and studied for polynucleotide transfer, the biological mechanisms and fate of the synthetic vehicle has remained elusive due to the limitations with current labeling(More)
Materials that self-assemble with nucleic acids into nanocomplexes (e.g. polyplexes) are widely used in many fundamental biological and biomedical experiments. However, understanding the intracellular transport mechanisms of these vehicles remains a major hurdle in their effective usage. Here, we investigate two polycation models, Glycofect (which slowly(More)
Baseline physiological function of the mammalian heart is under the constant threat of environmental or intrinsic pathological insults. Cardiomyocyte proteins are thus subject to unremitting pressure to function optimally, and this depends on them assuming and maintaining proper conformation. This review explores the multiple defenses a cell may use for its(More)
Understanding the mechanisms of cellular internalization is necessary for rational design of efficient polymers for DNA delivery. In this paper, we present evidence that poly(glycoamidoamine) (PGAA)-DNA complexes (polyplexes) interact with cell-surface glycosaminoglycans (GAGs) in a manner that is not solely dependent on charge. The presence of GAGs appears(More)