Molecular and Medical Geneticsbagby research

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Oregon Health & Science Univ
Molecular & Medical Genetics
Mail Code: L103
3181 SW Sam Jackson
Park Road
Portland, OR 97239
503-494-7703

Basic Science > Molecular and Medical Genetics > Faculty & Research Interests > Bagby Research

Grover C. Bagby, M.D. - Professor

NW VA Cancer Research Center
B103, E221B
3710 VA Hospital Road
Portland, OR 97239

Office: 503-220-8262
Fax: 503-721-7946

RESEARCH

Acute leukemias are hematopoietic malignancies that derive from single mutant hematopoietic stem cells. It is increasingly evident that the evolution of carcinomas follows these same general rules. The molecular biochemical pathways that permit the outgrowth of mutant progeny are not well understood. To identify such forces, we focus our molecular studies on normal cells, cancer cell lines, and cells from children and mice with Fanconi anemia, a rare autosomal recessive disorder characterized by bone marrow failure and subsequent leukemia and epithelial malignancies. We have discovered that mutations in the Fanconi genes impair growth factor signaling and induce programmed cell death in bone marrow progenitor cells and then proved that subsequent somatic mutations that reduce the rates of programmed cell death are required to initiate the malignant clone either in hematopoietic or epithelial cells. Having developed murine models that faithfully recapitulate the human disease Fanconi anemia and in vitro models that reveal quantifiable phenotypic alterations in human cells, we are seeking to define the defective signaling defects in detail, and to clarify the somatic mutations that occur in leukemic and cancer stem cells that result in resistance to apoptosis and clonal evolution. We have also developed genome wide evidence for clonal adaptation and a high-throughput screening assay based on the signaling defects we have defined in Fanconi anemia cells. We believe that this assay will be of value in identifying novel targeted therapeutic agents.

SELECT PUBLICATIONS

Pang, Q, Koretsky, T, Carlson, H, David, L, Keeble, W., Faulkner, G.R., Speckhart, A., Bagby, G.C. Nucleophosmin interacts with and inhibits the catalytic function of eukaryotic initiation factor 2 kinase PKR. J. Biol. Chem.278:41709-41717, 2003

Fagerlie, S., Koretsky, T.,Torok-Storb, B., Bagby, G.C. Impaired type I IFN-induced JAK/Stat signaling in FA-C cells and abnormal CD4+ T-helper cell subsets in Fancc -/-mice. J. Immunol. 173:3863-70, 2004.

Fagerlie, S., Bagby, G.C. Immune Defects in Fanconi Anemia, Critical Rev. Immunol. 26:81-96, 2006

Bagby, G.C., Alter, B.P. Fanconi Anemia, Seminars in Hematology 43:147-156, 2006

Pejovic,T., Yates,J.E., Liu,H.Y., Hays,L.E., Akkari,Y., Torimaru,Y., Keeble,W., Rathbun,R.K., Bale,A.E., Ameziane,N., Zwaan,C.M., Thuillier,P., Cappuccini,F., Olson,S.B. Cain,J.M., Bagby,G.C. Tissue specific cytogenetic instability in ovarian epithelial cells from women at risk of ovarian cancer. Cancer Research 66(18):9017-25. 2006

Li J, Sejas DP, Zhang X, Qiu Y, Nattamai KJ, Rani R, Rathbun KR, Geiger H, Williams DA, Bagby GC, Pang Q. TNF-alpha induces leukemic clonal evolution ex vivo in Fanconi anemia group C stem cells. J. Clin. Invest 117:3283-3295, 2007

Bagby GC, Discovering early molecular determinants of leukemogenesis, J. Clin. Invest. 118:847-850, 2008

Zhou,Y., Du,W., Koretsky,T., Bagby,G.C., Pang,Q. TAT-mediated intraceullar delivery of NPM-derived peptide induces apoptosis in leukemic cells and suppresses leukemogenesis in mice. Blood. 112:2474-83, 2008.

Pelz,C.R., Kulesz-Martin,M. Bagby,G., Sears, R.C. Global Rank-Invariant Set Normalization (GRSN) to reduce systematic distortions in microarray data. BioMed Central Bioinformatics (1291879293187588) 2008 (in press)

For more information on publications, contact the faculty member or search PubMed.

GRADUATE PROGRAM AFFILIATIONS:

PMCB

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