Dr. Owen Witte's laboratory is concerned with the interrelated problems of cell growth regulation/differentiation and understanding the function of oncogenes found in human leukemias and epithelial cancers. This includes the Bcr-Abl tyrosine kinase important in human chronic myelogenous leukemia. Witte and his colleagues also are interested in understanding the regulation of lymphocyte growth in disease states and during immune responses. They discovered that the gene defect in the primary immunodeficiency X-linked agammaglobulinemia is a single gene called Bruton's tyrosine kinase and are now studying its mode of action.
Recently, they identified a G protein-coupled receptor family which regulates inflammatory responses and autoimmunity and are studying its mechanisms of action. They are using positron emission tomography (PET) and other imaging modalities to study lymphocyte movement during the immune response as regulated by these receptors.
Prostate cancer is unique in its highly regularized pattern of metastasis to the bone marrow. One possible therapeutic target is PSCA (prostate homolog of hematopoietic stem cell antigen), expressed on a subset of prostate cells during active growth. Witte and his associates are using surface markers to fractionate normal murine prostate cell populations in an attempt to define an active stem cell population. They have used a recently developed dissociated cell reconstitution system, in which prostate epithelial stem and progenitor cells can be induced to form glandular tissue structures by embryonic urogenital sinus mesenchyme tissue when implanted under the kidney capsule, in order to study such stem cells.
Selected Cancer-Related Publications:
Lawson DA, Xin L, Lukacs RU, Cheng D, Witte ON. Isolation and functional characterization of murine prostate stem cells. Proc Natl Acad Sci U S A. 2007; 104(1): 181-6.
Rawlings DJ, Scharenberg AM, Park H, Wahl MI, Lin S, Kato RM, Fluckiger AC, Witte ON, Kinet, JP. Activation of Btk by a phosphorylation mechanism initiated by src family kinases. Science. 1996; 271:822-825.
Tsukada S, Saffran DC, Rawlings DJ, Parolini O, Allen RC, Klisak I, Sparkes RS, Kubagawa H, Mohandas T, Quan S, Belmont JW, Cooper MD, Conley ME, Witte ON. Deficient expression of a B-Cell cytoplasmic tyrosine kinase in human x-linked agammaglobulinemia. Cell. 1993; 72:279-290.
Gishizky ML, Witte ON. Initiation of deregulated growth of multipotent progenitor cells by BCR/ABL in vitro. Science. 1992; 256:836-839.
Konopka JB, Watanabe SM, Witte ON. An alteration of the human c-abl protein in K562 leukemia cells unmasks associated tyrosine kinase activity. Cell. 1984; 37:1035-1042.