Multifunctional Nanomaterials and Their Applications in Drug Delivery and Cancer Therapy.

The field of nanotechnology has led to the development of many innovative strategies for effective detection and treatment of cancer, overcoming limitations associated with conventional cancer diagnosis and therapy. Multifunctional nanoparticle systems can integrate imaging, targeting and treatment moieties on the surface and in the core, resulting in targeted delivery of the imaging or treatment modalities, specifically to the tumor. Multifunctional nanoparticles also enable simultaneous delivery of multiple treatment agents, resulting in effective combinatorial therapeutic regimens against cancer.

Influence of prion variant and yeast strain variation on prion-molecular chaperone requirements.

Prions of budding yeast serve as a tractable model of amyloid behavior. Here we address the issue of the effect of yeast strain variation on prion stability, focusing also on the effect of amyloid conformation and the involvement of the co-chaperone Sis1, an essential J-protein partner of Hsp70. We found, despite an initial report to the contrary, that yeast strain background has little effect on the requirement for particular Sis1 domains for stable propagation of the prion [RNQ+], if the level of Sis1 expression is controlled.

Donor B-cell alloantibody deposition and germinal center formation are required for the development of murine chronic GVHD and bronchiolitis obliterans.

Chronic GVHD (cGVHD) poses a significant risk for HSCT patients. Preclinical development of new therapeutic modalities has been hindered by models with pathologic findings that may not simulate the development of human cGVHD. Previously, we have demonstrated that cGVHD induced by allogeneic HSCT after a conditioning regimen of cyclophosphamide and total-body radiation results in pulmonary dysfunction and airway obliteration, which leads to bronchiolitis obliterans (BO), which is pathognomonic for cGVHD of the lung.

Peripheral tolerance in CD8+ T cells.

The establishment and maintenance of T cell tolerance to self- and non-pathogenic foreign antigens is critical for immune homeostasis. Thymic deletion of self-reactive T cells is an important component of tolerance, but it is incomplete, and does not establish tolerance to most foreign antigens. Thus, mechanisms of peripheral tolerance are also required.

Reciprocal NFAT1 and NFAT2 nuclear localization in CD8+ anergic T cells is regulated by suboptimal calcium signaling.

Anergy is an important mechanism of maintaining peripheral immune tolerance. T cells rendered anergic are refractory to further stimulation and are characterized by defective proliferation and IL-2 production. We used a model of in vivo anergy induction in murine CD8+ T cells to analyze the initial signaling events in anergic T cells.