Scott A. Ness, PhD
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 121
Tel: 505-272-9883
Email: sness@salud.unm.edu
Scott A. Ness received his B.A. in biology at the University of California, San Diego in La Jolla, CA in 1980 and his Ph.D. in biochemistry from the Department of Chemistry and Biochemistry at the University of California, Los Angeles in 1985. He did post-doctoral research at the European Molecular Biology Laboratory in Heidelberg, Germany, in the laboratory of Dr. Thomas Graf, studying oncogenes, transcription and leukemia. Dr. Ness started his own laboratory at Northwestern University in Evanston, IL in 1991 and moved to UNM Health Sciences Center in 1998.
The Ness laboratory studies cancer cell biology, the relationship between oncogenes and transcriptional regulation, hematopoietic stem cells and the control of cell fate. Our work focuses on the c-Myb and v-Myb transcription factors, and regulatory proteins that control their activity. The Ness lab uses genomics and bioinformatics approaches in combination with biochemistry, molecular biology and cellular biology. We apply these various types of tools to perform highly innovative basic and translational research.
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.
Research in the Ness Lab
How does a stem cell become a differentiated, specialized cell? How does a normal cell become transformed into a tumor cell? These are the basic questions that the Ness laboratory is addressing.
We use a variety of genetic, molecular biology, cell biology and biochemical methods to study how gene regulation changes as cells differentiate from an immature stem cell precursor to a mature, specialized cell. We also study how gene regulation changes when normal cells become tumor cells.
By understanding the mechanisms controlling gene expression and the regulation of specific genes in different cell types, during differentiation and during tumorigenesis, we hope to identify novel targets and techniques that could be used for developing new therapeutic or diagnostic approaches to treating leukemias, solid tumors and stem cell diseases.
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.
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.
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.
(To see all publications, visit ORCID ID: orcid.org/0000-0001-6965-8909)
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
Matlawska-Wasowska, K., et al., MLL rearrangements impact outcome in HOXA-deregulated T-lineage acute lymphoblastic leukemia: a Children's Oncology Group Study. Leukemia, 2016. 30(9): p. 1909-12. PMC5014577
Brayer, K.J., C.A. Frerich, H. Kang, and S.A. Ness, Recurrent Fusions in MYB and MYBL1 Define a Common, Transcription Factor-Driven Oncogenic Pathway in Salivary Gland Adenoid Cystic Carcinoma. Cancer Discov, 2016. 6(2): p. 176-87. PMC4744535
Mayfield, J.R., et al., Integration of ruxolitinib into dose-intensified therapy targeted against a novel JAK2 F694L mutation in B-precursor acute lymphoblastic leukemia. Pediatr Blood Cancer, 2017. 64(5). PMC5366086
Rajput, A., T. Bocklage, A. Greenbaum, J.H. Lee, and S.A. Ness, Mutant-Allele Tumor Heterogeneity Scores Correlate With Risk of Metastases in Colon Cancer. Clin Colorectal Cancer, 2017. 16(3): p. e165-e170. PMC5441963
Brown, R.B., N.J. Madrid, H. Suzuki, and S.A. Ness, Optimized approach for Ion Proton RNA sequencing reveals details of RNA splicing and editing features of the transcriptome. PLoS One, 2017. 12(5): p. e0176675. PMC5411089
Frerich, C.A., K.J. Brayer, B.M. Painter, H. Kang, Y. Mitani, A. El-Naggar, and S.A. Ness, Transcriptomes define distinct subgroups of salivary gland adenoid cystic carcinoma with different driver mutations and outcomes. Oncotarget, 2018. 9(7): p. 7341-7358. PMC5800907
Greenbaum A., Martin D., Bocklage T., Lee J-H., Ness, S., Rajput A. Tumor Heterogeneity as a Predictor of Response to Neoadjuvant Chemotherapy in Locally-Advanced Rectal Cancer. Clinical Colorectal Cancer. 2019 Feb 13. pii: S1533-0028(18)30597-8. doi: 10.1016/j.clcc.2019.02.003. PMID: 30935775
Frerich CA, Sedam HN, Kang H, Mitani Y, El-Naggar AK, Ness SA, N-Terminal Truncated Myb with New Transcriptional Activity Produced Through Use of an Alternative MYB Promoter in Salivary Gland Adenoid Cystic Carcinoma. Cancers (Basel). 2019 Dec 21;12(1). pii: E45. doi: 10.3390/cancers12010045. PMID: 31877778
Yu, H., S. Zhao, S. Ness, H. Kang, Q. Sheng, D.C. Samuels, O. Oyebamiji, Y.Y. Zhao, and Y. Guo, Non-canonical RNA-DNA differences and other human genomic features are enriched within very short tandem repeats. PLoS Comput Biol, 2020. 16(6): p. e1007968. PMC7302867
Sheng, Q., H. Yu, O. Oyebamiji, J. Wang, D. Chen, S. Ness, Y.Y. Zhao, and Y. Guo, AnnoGen: annotating genome-wide pragmatic features. Bioinformatics, 2020. 36(9): p. 2899-2901. PMC7203733
Lee, D.Y., K.J. Brayer, Y. Mitani, E.A. Burns, A. Rao, D. Bell, M.D. Williams, R. Ferrarotto, K.B. Pytynia, A.K. El-Naggar, and S.A. Ness, Oncogenic Orphan Nuclear Receptor NR4A3 Interacts and Cooperates with MYB in Acinic Cell Carcinoma. Cancers (Basel), 2020. 12(Aug 27): p. E2433. PMC7565926
Learn More
Our laboratory is in the Cancer Research Facility, part of the Health Sciences Center on the North Campus of the University of New Mexico, in Albuquerque, NM.
Current Members of the Ness Laboratory (2021):
Post-Doctoral Researchers:
Recent: Olivia George (now faculty at the Univ of Hawaii)
Graduate Students:
Recent: Candace Frerich (now at UTSW)
Research Technicians:
Maggie Cyphery
Jennifer B. Woods
Bioinformatics Staff Scientists:
Kathryn (Charlie) Brayer
Roger Brown
For information about our graduate program, see the Biomedical Sciences Graduate Program web page.
For information about the postdoc position in the Ness Lab, visit the UNMCCC Postdoctoral and Graduate Opportunities page.