MICaB Graduate Program
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Brian VanNess, Ph.D.
Department of Genetics, Cell Biology, and Development.
University of Minnesota, 1979, Ph.D.
Areas of research strength:
- Gene expression
- Human genetics
- Immunology, cancer genetics
Research techniques used:
- Diagnostic PCR
- Homologous recombinations
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.
- 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
- 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.
- 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
- 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