Arsenic trioxide (As<sub>2</sub>0<sub>3</sub>) is an arsenic-derivative that exhibits potent growth inhibitory effects against malignant cells. The remarkable antitumor effects of As<sub>2</sub>0<sub>3</sub> in vitro and in vivo have prompted the development of various clinical trials that established its activity in acute promyelocytic leukemia (APL). As<sub>2</sub>0<sub>3</sub> is part of the standard treatment...
Reactivation of latent human cytomegalovirus is of significant concern in immunocompromised transplant patients. However, the mechanisms controlling reactivation of latent CMV have not been understood. It is likely that reactivation is initiated by induction of IE gene expression. In this thesis, I studied molecular mechanisms leading to transcriptional activation of...
CD4-positive T cells express ligands for E- and P-selectins, carbohydrate-binding adhesion molecules that are induced on inflamed endothelium. The interaction between selectins and the selectin ligands facilitates the migration of T cells to sites of inflammation. The fucosyltransferase FucT-VII is essential for selectin ligand formation but the signaling and transcriptional...
In the process of development of a multicellular organism, cells must make stable, binary fate decisions in response to intercellular signaling. A critical question is how weak or transient activation of signaling pathways achieves a robust and long-term switch in gene expression, and thus determines cell fate. I report that...
The formation of neuronal inclusions is one of the hallmarks of neurodegenerative diseases. These structures are composed of aggregated proteins, molecular chaperones, and components of the ubiquitin-proteasome system (UPS). Co-localization of aggregated proteins with cell-homeostasis maintaining machinery indicates that the cell may be failing in an attempt to clear these...
Understanding the nature of quantum effects in dense biological systems is of great interestto many scientists today. It seems that the question is not does quantum mechanics dictatebiological processes, but rather by how much and to what extent. A big challenge though in thisfield is how to properly test and...
E2F-2 is a Retinoblastoma (Rb)-regulated transcription factor induced during terminal erythroid maturation. Cyclin E-mediated Rb hyper-phosphorylation induces E2F transcriptional activator functions. E2F-2-loss causes reduced peripheral red blood cell (RBC) counts, without altering relative abundances of erythroblast subpopulations. To determine how E2F-2 regulates RBC production, we comprehensively studied erythropoiesis using knockout...