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:
Drake JM, Graham NA, Stoyanova T, Sedghi A, Goldstein AS, Cai H, Smith DA, Zhang H, Komisopoulou E, Huang J, Graeber TG, Witte ON. Oncogene-specific activation of tyrosine kinase networks during prostate cancer progression. Proc Natl Acad Sci U S A. 2012 Jan 31;109(5):1643-8. Epub 2012 Jan 17
Goldstein AS, Huang J, Guo C, Garraway IP, Witte ON. Identification of a cell of origin for human prostate cancer. Science. 2010 Jul 30;329(5991):568-71.
Lukacs RU, Memarzadeh S, Wu H, Witte ON. Bmi-1 is a crucial regulator of prostate stem cell self-renewal and malignant transformation. Cell Stem Cell. 2010 Dec 3;7(6):682-93.
Radu CG, Shu CJ, Nair-Gill E, Shelly SM, Barrio JR, Satyamurthy N, Phelps ME, Witte ON. Molecular imaging of lymphoid organs and immune activation by positron emission tomography with a new [18F]-labeled 2'-deoxycytidine analog. Nat Med. 2008 Jul;14(7):783-8. Epub 2008 Jun 8
Memarzadeh S, Xin L, Mulholland DJ, Mansukhani A, Wu H, Teitell MA, Witte ON. Enhanced paracrine FGF10 expression promotes formation of multifocal prostate adenocarcinoma and an increase in epithelial androgen receptor. Cancer Cell. 2007 Dec;12(6):572-85.