Brian VanNess, Ph.D. Professor Department of Genetics, Cell Biology, and Development. University of Minnesota, 1979, Ph.D. vanne001@umn.edu 612-624-9944 office 612-624-9663 lab

Research Interests:

Areas of research strength:

• Gene expression
• Human genetics
• Immunology, cancer genetics

Research techniques used:

• Diagnostic PCR
• Transfections
• Transgenics
• Homologous recombinations

Research interest:

Our research is directed at understanding the regulation of the immune system: in particular, how antobody or immunoglobulin genes are activated and regulated in B-lymphoid cells. We are especially interested in the DNA rearrangements that are required to express antibody genes. To understand these mechanism, we are transfecting a variety of mouse and human cell cultures with genetically engineered DNA constructs. We have also bred transgenic mice to help us understand how these gene constructs are regulated in intact animals. Our work has enabled us to identify DNA elements and proteins that serve to activate or suppress immunoglobulin gene expression. Our future efforts are directed toward an understanding of how the regulatory elements are coordinately regulated during the life of a B cell. In a related research program, we and our clinical colleagues are using a variety of molecular approaches, including PCR-based diagnosis, to monitor and characterize malignant myeloma and leukemia cells. We are particularly interested in defining genetic abnormalities that give rise to maligancy, including anlaysis of oncogenes. We are continuing to develop both cell culture and mouse models of lymphoid malignancy in order to characterize the effects of genetically manipulated cells on disease progression and response to therapy. .

Selected Recent Publications:

• Prabhu, A., O'Brien, D., Weisner, G., Fulton, R., and Van Ness, B. (1996) Octamer independent activation of transcription from the kappa immunoglobulin germline promoter. Nucleic Acids Res. 24:4805-4811.
• Liu, P., Leong, T., Quam, L., Billadeau, D., Kay, N., Greipp, P., Kyle, R., Oken, M., and Van Ness, B. (1996) Activating mutations of N- and K-ras in multiple myeloma show different clinical associations: Analysis of the Eastern Cooperative Oncology Group Phase III Trial E9486. Blood. 88:2699-2706.
• LeBien T, Van Ness B, Billadeau D, Liu P, Shah N, Jelinek D : Activating mutations in the N-and K-ras oncogenes differentially affect the growth properties of the IL-6 dependent myeloma cell line ANBL6. Cancer Res 57:2268, 1997a.
• Verfaillie C, Weisdorf D, Van Ness B, Billadeau D, Prosper F : Sequential analysis of bone marrow and peripheral blood after stem cell transplant for myeloma shows disparate tumor involvement. Leukemia 1997b.
• Billadeau, D. Liu, P., Shah, N., LeBien, T., Jelinek, D., and Van Ness, B. (1997) Activating mutations in the N- and K-ras oncogenes differentially affect the growth properties of the IL-6 dependent myeloma cell line ANBL6. Cancer Research. 57: 2268-2275.
• Billadeau, D., Prosper, F., Verfaillie, K., Weisdorf, D., and Van Ness, B. (1997) Sequential analysis of bone marrow and peripheral blood after stem cell transplant for myeloma shows disparate tumor involvement. Leukemia. 11:1565-1570.
• O'Brien, D., Oltz, E., and Van Ness. (1997) Coordinate transcription and V(D)J recombination of the kappa immunoglobulin light chain locus: NF-kB dependent and independent pathways of activation. Mol. Cell. Biol. 17:3477-3487.
• Van Ness B, Oken MM, Kay N, Leong T, Kyle RA, Greipp P, Billadeau D, Bone N: Circulating blood B cells in multiple myeloma: Analysis and relationship to circulating clonal cells and clinical paramters in a cohort of patients entered on the ECOG phase III E9486 Clinical Trial. Blood 90:340, 1997.
• Liu, P., Oken , M, and Van Ness, B. (1999). Interferon-a protects myeloma cell lines from dexamethasone induced apoptosis. Leukemia. 13, 473-480.
• Liu, X., Prabhu, A., and Van Ness, B. (1999) Developmental regulation of the k locus involves both positive and negative sequence elements in the 3' enhancer that affect synergy with the intron enhancer. J. Biol. Chem. 274:3285-3293.
• Liu, X and Van Ness, B. (1999) Gene targeting of the KI-KII sequence elements in a model pre-B cell line: Effects on germline transcription and rearrangement of the k locus. Molecular Immunol. 36:461-469.
• Rowley, M., Liu, P., and Van Ness, B. (2000) Heterogeneity in therapeutic response of genetically altered myeloma cell lines to IL-6, Dexamethasone, Doxorubicin, and Melphalan. Blood 96:3175-80.