Scott A. Ness, PhD

Scott Ness photo

The Victor and Ruby Hansen Surface Endowed Professor in Cancer Genomics 
UNM Comprehensive Cancer Center Associate Director for Shared Resources
Professor of Molecular Medicine, Department of Internal Medicine
Director, Analytical and Translational Genomics Shared Resource

Office: CRF 104
Tel:  505-272-9883
Email:  sness@salud.unm.edu

Information about: Members of my laboratory
Information about: Post Doc positions in my laboratory
Find my publications: NCBI Bibliography

The research in my laboratory extends from basic science to translational research to technology development. My laboratory applies molecular and genomics approaches to do innovative studies concerning the regulation of gene expression in normal and cancer cells. The following paragraphs summarize our major research projects:

Basic Science: How do signaling and upstream pathways control the activities of c-Myb?

The c-Myb transcription factor is a key and essential regulator of hematopoiesis and plays important roles in epithelial and some neural cells. The two striking features of c-Myb are that it regulates different sets of genes in different situations and that relatively minor mutations can completely change its activity – even converting the normal regulator into an oncoprotein. One aspect of my research is to better understand how the activities of c-Myb are regulated and affected by protein-protein interactions and upstream regulatory and signal transduction pathways that lead to changes in post-translational modifications. We have developed novel and innovative approaches for following changes in c-Myb during the cell cycle and are mapping domains in the protein responsible for cell cycle-dependent changes in transcriptional activities. We are using whole genome techniques such as Chromatin Immunoprecipitation coupled with next-generation sequencing (ChIP-seq) to map global changes in the association of c-Myb with promoters during different stages of the cell cycle and to compare the activities of the wild type protein to the oncogenic alleles. The goals are to understand how signaling pathways lead to changes in c-Myb activity and how the activity of c-Myb becomes corrupted in cancer cells. A better understanding of the regulatory pathways that control c-Myb activity should lead to novel therapeutic approaches for treating cancer patients.

Translational Research: Developing novel imaging assays and drug screens.

The c-Myb protein is a critical regulator of cell fate, controlling whether cells continue proliferating or differentiate. We found that the c-myb gene encodes at least 60 different splice variants, and that the expression of specific variants correlates with poor prognosis and poor survival in leukemia patients (manuscript in preparation). This provides a novel type of biomarker for analyzing and classifying leukemia patients, and we have developed high-throughput methods using next-generation sequencing technologies to take advantage of this approach. We have also found that the c-Myb protein is tightly regulated and that its specificity and targeting to specific genes is controlled by upstream signaling pathways that affect protein-protein interactions. This provides a novel approach for screening potential therapeutic agents that can lead to changes in c-Myb activities and determine whether cancer cells continue to proliferate or are triggered to differentiate. We have several projects designed to target the differentiation-promoting activity of c-Myb that could lead to new clinical trials.

Technology Development: Applying next-generation assays to RNAs and proteins.

As the Director of our genomics shared resource, I have made use of new types of genomics technologies for my own NCI- and NIDCR-funded research, and I have been involved in the development of new types of technologies for improving and lowering the cost of next-generation DNA sequencing. We are also working on novel ways of utilizing the amazing power of next-generation sequencing technologies and bioinformatics for the analysis of protein-protein interactions and post-translational modifications. These approaches could open new doors for the analysis and understanding of populations and sub-populations of proteins in the cell.

Selected Publications

Ness, S. A., Beug, H., and Graf, T. (1987). v-myb dominance over v-myc in doubly transformed chick myelomonocytic cells. Cell 51, 41-50.

Ness, S. A., Marknell, Å., and Graf, T. (1989). The v-myb oncogene product binds to and activates the promyelocyte-specific mim-1 gene. Cell 59, 1115-1125.

Ness, S. A., Kowenz-Leutz, E., Casini, T., Graf, T., and Leutz, A. (1993). Myb and NF-M:  Combinatorial activators of myeloid genes in heterologous cell types. Genes Dev 7, 749-759.

Dash, A. B., Orrico, F. C., and Ness, S. A. (1996). The EVES motif mediates both intermolecular and intramolecular regulation of c-Myb. Genes Dev 10, 1858-1869. PMID: 8756344.

Leverson, J. D., Koskinen, P. J., Orrico, F. C., Rainio, E.-M., Jalkanen, K. J., Dash, A. B., Eisenman, R. N., and Ness, S. A. (1998). Pim-1 Kinase and p100 Cooperate to Enhance c-Myb Activity. Molecular Cell 2, 417-425. PMID: 9809063.

Leverson, J. D., and Ness, S. A. (1998). Point Mutations in v-Myb Disrupt a Cyclophilin-Catalyzed Negative Regulatory Mechanism. Molecular Cell 1, 203-211. PMID: 9659917.

Rushton, J. J., Davis, L. M., Lei, W., Mo, X., Leutz, A., and Ness, S. A. (2003). Distinct changes in gene expression induced by A-Myb, B-Myb and c-Myb proteins. Oncogene 22, 308-313. PMID: 12527900.

Winn, L. M., Lei, W., and Ness, S. A. (2003). Pim-1 Phosphorylates the DNA Binding Domain of c-Myb. Cell Cycle 2, 258-262. PMID: 12734436.

Lei, W., Rushton, J. J., Davis, L. M., Liu, F., and Ness, S. A. (2004). Positive and negative determinants of target gene specificity in Myb transcription factors. J Biol Chem 279, 29519-29527. PMID: 15105423.

Lei, W., Liu, F., and Ness, S. A. (2005). Positive and Negative Regulation of c-Myb by Cyclin D1, Cyclin-Dependent Kinases and p27 Kip1. Blood 105, 3855-3861. PMCID: PMC1895079

Liu, F, Lei, W, O'Rourke, JP and Ness, SA. (2006) Oncogenic mutations cause dramatic, qualitative changes in the transcriptional activity of c-Myb. Oncogene 25, 795-805. PMID: 16205643.

O'Rourke, JP and Ness, SA. (2008) Alternative RNA Splicing Produces Multiple Forms of c-Myb with Unique Transcriptional Activities. Mol Cell Biol. 28(6):2091-101. PMCID: PMC2268396

Quintana AM, Liu F, O’Rourke JP and Ness SA. (2011) Identification and Regulation of c-Myb Target Genes in MCF-7 Cells. BMC Cancer, Jan 25; 11(1): 30. PMCID: PMC3038977 (Highly Accessed)

Quintana AM, Zhou YE, Pena JJ, O’Rourke JP and Ness SA (2011) Dramatic repositioning of c-Myb to different promoters during the cell cycle observed by combining cell sorting with chromatin immunoprecipitation. PLoS One. 2011 Feb 22;6(2):e17362. PMCID: PMC3043100

Zhou YE, O’Rourke JP, Edwards JS and Ness SA. (2011) Single Molecule Analysis of c-myb Alternative Splicing Reveals Novel Classifiers for Precursor B-ALL. PLoS One. 2011;6(8):e22880. Epub 2011 Aug 11. PMCID: PMC3154906.

Suzuki H, Yu J, Ness SA, O'Connell MA, Zhang J. RNA editing events in mitochondrial genes by ultra-deep sequencing methods: a comparison of cytoplasmic male sterile, fertile and restored genotypes in cotton. Mol Genet Genomics. 2013 Sep;288(9):445-57. doi: 10.1007/s00438-013-0764-6. Epub 2013 Jun 29. PMID: 23812672

George OL, Ness SA. Situational awareness: regulation of the myb transcription factor in differentiation, the cell cycle and oncogenesis. Cancers (Basel). 2014 Oct 2;6(4):2049-71. doi: 10.3390/cancers6042049. Review.
PMID: 25279451

Brayer KJ, Frerich CA, Kang H, Ness SA. Recurrent Fusions in MYB and MYBL1 Define a Common, Transcription Factor-Driven Oncogenic Pathway in Salivary Gland Adenoid Cystic Carcinoma. Cancer Discov. 2015 Dec 2. [Epub ahead of print] PMID: 26631070