Assistant Professor, Eppley InstituteTel: 402-559-8573 (Office),
E-mail: Mayumi Naramura
We are interested in understanding the biochemical pathways controlling stem cell homeostasis and differentiation.
Summary of Research
Maintenance of normal body functions require tightly regulated communications between cells as well as between cells and their surroundings. Much of this information is transmitted through cell surface receptors.
Upon ligand binding, a typical receptor tyrosine kinase (RTK) dimerizes, trans-phosphorylates cytoplasmic tails, and initiates a cascade of enzymatic reactions that culminate in cell proliferation, cell death, migration or differentiation. Traditionally, more efforts have been dedicated to elucidate the biochemical pathways that convey positive signals. However, recent studies have established that mechanisms of signal attenuation/termination is equally important to maintain the fine balance in physiological cellular functions. One of the mechanisms of signal attenuation/termination is receptor internalization and degradation. It has been demonstrated that ligand-activated receptors are cleared from the cell surface by endocytosis and eventually degraded in the lysosome. But a certain fraction of internalized receptors recycle back to the cell surface for another round of ligand-binding and activation.
What, then, determines the receptor fate between degradation and recycling? Experimental evidences indicate that modification with ubiquitin serves as a tag for degradation for a wide variety of proteins. Cbl family proteins are ubiquitin ligases that are specifically recruited to activated RTKs and promote ubiquitinylation. With recent identification of Cbl mutations in cancer patients, its critical role in signal regulation is now well established.
Using mouse models developed in our laboratory, we are investigating the role of Cbl proteins in the hematopoietic systems. We are also studying the role of Cbl proteins in mammary epithelial cells using a novel in vitro-differentiating cell line model. These studies are aimed at elucidating fundamental biological processes and leveraging the knowledge into novel diagnostics and therapeutics.