The Ness laboratory uses innovative approaches to study important topics at the interface between cancer biology, molecular biology, stem cells, differentiation, transcription, epigenetics and genomics. Many of the research topics in our laboratory revolve around the regulation of the transcription factor c-Myb, which regulates the expression of lineage-specific genes in differentiating hematopoietic cells. The c-Myb protein regulates different genes in different hematopoietic cell types, and it regulates different genes in different parts of the cell cycle, so it must respond to different upstream signals in order to induce the expression of lineage-specific genes in different situations. We are studying the post-translational modifications and protein-protein interactions that control the activity of c-Myb in order to understand the molecular basis of differentiation and the control of cell fate.
The c-Myb protein is the normal cellular counterpart to v-Myb, a transforming protein expressed by two avian leukemia viruses that transforms immature hematopoietic cells and induces leukemias in chickens and mice. The v-Myb protein is a mutated and activated version of c-Myb. Thus, the mutations in v-Myb appear to have unmasked the latent oncogenic potential in the c-Myb protein, using the ability of c-Myb to control differentiation and proliferation to transform cells and induce leukemia. The expression levels and activities of c-Myb are modified in numerous types of human tumors including leukemias, lymphomas, colon tumors, breast tumors and a special class of salivary gland tumors called adenoid cystic carcinomas. We study how the changes in c-Myb affect its activities and lead to tumorigenesis.
Our laboratory uses a wide variety of different methods and techniques including molecular biology, cell biology, genetics and biochemistry. We have developed specialized adenovirus and lentivirus vectors for expressing wild type and mutant alleles of c-Myb in many different human cells, including human hematopoietic stem cells. We use microarrays, genomics and next-gen sequencing approaches to study the activities of Myb proteins in human cells, and assays of differentiation, proliferation and apoptosis to assess the biological effects.
The Ness laboratory has been continuously supported by grants from NIH, ACS and other foundations for over 20 years and is currently supported by two grants from the National Cancer Institute and one from the Adenoid Cystic Carcinoma Research Foundation. Dr. Ness is Associate Director of the UNM Cancer Center (in charge of all shared resources) and is Director of the Keck-UNM Genomics and Bioinformatics Shared Resource.
Some of the projects we are currently working on include:
• Regulation of c-Myb during the cell cycle (supported by an NCI R01 grant)
• Characterizing the activities of c-Myb in solid tumors (supported by a grant from the Adenoid Cystic Carcinoma Research Foundation, ACCRF)
• Using next-gen sequencing to analyze and determine the importance of alternative RNA splicing in pediatric leukemia (supported by a Provocative Questions R01 from NCI)