Research Interest

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RNA-binding proteins play an important role in post-transcriptional gene regulation. They must bind to the correct target RNAs for proper splicing, mRNA decay, translation, etc. to occur. In our lab we study RNA-binding proteins that may play a role in gene deregulation. The main focus of the lab is the family of RNA-binding proteins called Hu proteins. Three of the four Hu proteins are normally expressed in healthy neurons but can be overexpressed in certain kinds of cancer such as neuroblastoma and small cell lung cancer (SCLC). We are analyzing their possible role in cancer as well as their biochemical function. SCLC is a lethal disease that kills over 30,000 Americans per year. Very little is known about the early molecular changes in SCLC, because most patients have advanced cancer at the time of diagnosis. Treatments are ineffective, resulting an a median patient survival of 10-16 months in the best of cases, and often less if the tumor has spread throughout the body at the time of diagnosis. We are studying the role of Hu proteins in the development and progression of SCLC, and their possible use in cancer diagnosis. We have also recently embarked on our first ever collaborative project with Peter Laird (Ite's better half), and are studying DNA methylation in lung cancer. Increasing our knowledge of the identity and timing of the molecular changes occurring during the progression of lung cancer is essential for the development of new diagnostic and therapeutic approaches.

The more basic science interest of the lab is the study of the mechanism by which RNA-binding proteins can bind tightly and specifically to their RNA targets. We are studying proteins carrying RNA-binding domains of the RRM (RNA recognition motif) type. RRMs are the most common RNA-binding domain and are found in hundreds of RNA-binding proteins. These baseball glove-shaped domains are also referred to as RNP consensus domains or RNA binding domains (RBDs). Proteins can carry one or more RRMs, which allows them to bind to a wide variety of RNA sequences and structures. We are analyzing the interaction between the three RRMs of Hu proteins and single-stranded AU-rich RNA, as well as the interaction between the N-terminal RRM of the spliceosomal U1A protein and its hairpin RNA target in U1 small nuclear RNA. Among others, we use surface plasmon resonance (BIACORE) to study these RNA-protein interactions, because this technology allows us to gain a detailed insight into the kinetics of complex formation. Attaining a kinetic understanding of these interactions is important because biological systems are dynamic; the ability of a given protein to form a stable complex with RNA will affect its ability to compete for binding with other proteins, and to co-localize with an RNA, for example during nuclear export.