Unraveling neurovascular mysteries: the role of endothelial glycocalyx dysfunction in Alzheimer's disease pathogenesis.

While cardiovascular disease, cancer, and human immunodeficiency virus (HIV) mortality rates have decreased over the past 20 years, Alzheimer's Disease (AD) deaths have risen by 145% since 2010. Despite significant research efforts, effective AD treatments remain elusive due to a poorly defined etiology and difficulty in targeting events that occur too downstream of disease onset. In hopes of elucidating alternative treatment pathways, now, AD is commonly being more broadly defined not only as a neurological disorder but also as a progression of a variety of cerebrovascular pathologies highlighted by the breakdown of the blood-brain barrier.

Bacterial delivery of therapeutic proteins to the nuclei of cancer cells.

Targeting nucleic targets with therapeutic proteins would enhance the treatment of hard-to-treat cancers. However, exogenous proteins are excluded from the nucleus by both the cellular and nuclear membranes. We have recently developed Salmonella that deliver active proteins into the cytoplasm of cancer cells.

Developing a transwell millifluidic device for studying blood-brain barrier endothelium.

Blood-brain barrier (BBB) endothelial cell (EC) function depends on flow conditions and on supportive cells, like pericytes and astrocytes, which have been shown to be both beneficial and detrimental for brain EC function. Most studies investigating BBB EC function lack physiological relevance, using sub-physiological shear stress magnitudes and/or omitting pericytes and astrocytes. In this study, we developed a millifluidic device compatible with standard transwell inserts to investigate BBB function.

Dearomatization of Heteroarenium Salts with ArBpin Reagents. Application to the Total Synthesis of a Nuphar Alkaloid.

Rhodium-catalyzed enantioselective addition of aryl and heteroaryl boron pinacol esters to pyridinium and quinolinium salts is developed for the synthesis of enantioenrichred dihydroheteroarenes. The methodology has enabled the synthesis of 2-heteroaryl-substituted dihydropyridines in high yield and ee, which provided efficient synthetic access to a nuphar alkaloid.