Ralph B. Arlinghaus, Ph.D.

1961, University of Cincinnati

UT M. D. Anderson Cancer Center
Molecular Pathology

Research Interests: Viral and cellular oncogenes; protein kinases; HIV drug therapy and vaccines

A major objective of my research is to elucidate physiologically important molecular mechanisms involved in conversion of normal cells to neoplastic cells by activated oncogenes. Special emphasis is placed on the bcr-able oncoprotein derived from fused bcr and abl genes present in Philadelphia chromosome-positive chronic myelogenous leukemia patients. Our results demonstrate that the Bcr and Abl proteins downregulate each others kinase activity; Abl inhibition of Bcr becomes dominant as a result of the bcr-abl fusion. Strategies for therapeutic approaches to treat these leukemias are being pursued. Studies involving factors secreted by Bcr-Abl positive cells are being pursued. One of these factors induces cell death in normal blood cells; Bcr-Abl expressing cells are resistant to these cell death effects, resulting in the enhancement of the growth of leukemia cells in marrow and spleen tissue.

A tutorial could provide exposure to techniques including recombinant DNA methods, transient transfection assays, expression of viral proteins in mammalian cells, in vivo transcription and translation assays, synthetic peptides and their use as immunogens to raise anti-peptide antibodies, cytotoxic T lymphocytes, immunoblotting, protein kinase assays and immunological/ biochemical characterization of proteins.
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Liu J, Wu Y, and Arlinghaus RB (1996) Sequences within the first exon of BCR inhibit the activated tyrosine kinase of c-Abl and the Bcr-Abl oncoprotein. Cancer Res 56:5120-5124.

Wu Y, Liu J, Arlinghaus RB (1998) Requirement of two specific tyrosine residues for the catalytic activity of Bcr serine/threonine kinase. Oncogene 16:141-146.

Wang Y, Liu J, Wu Y, Luo W, Lin S-H, Lin H, Hawk N, Sun T, Guo JQ, Estrov Z, Talpaz M, Champlin R, Arlinghaus RB (2001) Expression of a truncated first exon BCR sequence in chronic myelogenous leukemia cells blocks cell growth and induces cell death. Cancer Res 61:138-144.

Lin F, Monaco P, Sun T, Liu J, Lin H, Stephens C, Belmont J, Wang Y, Arlinghaus RB (2001) BCR gene expression blocks Bcr-Abl induced pathogenicity in a mouse model. Oncogene 20:1873-1881.

Hawk N, Sun T, Xie S, Wang Y, Wu Y, Liu J, Arlinghaus RB (2002) Inhibition of the Bcr-Abl oncoprotein by Bcr requires phosphoserine 354. Cancer Research 62:386-390.

Ling X, Ma G, Sun T, Liu J, Arlinghaus RB (2003) Bcr and Abl interaction: Oncogenic activation of c-Abl by sequestering Bcr. Advances in Brief, Cancer Research 61:198-303.

Program Affiliations:
Program in Molecular Pathology
Program in Virology and Gene Therapy