Faculty

Department / Division Affiliations

Member, JCCC Hematopoietic Malignancies Program Area, JCCC Tumor Immunology Program Area

ACCESS Affinity Group:

ACCESS Affinity - Stem Cell Biology

Research Interest:
We are interested in the development of the immune response, growth regulation mechanisms used in leukemias and during metastasis of certain epithelial cancers to the bone marrow, and the application of new quantitative processes of whole-animal imaging. We have used positron emission tomography (PET) reporter gene strategies to mark populations of lymphocytes reactive to antigens on solid tumors and follow lymphocyte homing and expansion in living mice. Many of these techniques may be suitable for evaluation of human anti-tumor responses. Our laboratory has contributed major findings in the following areas: (i) The Role of the BCR-ABL Oncogene in Leukemias: We have demonstrated that this kinase is critical for the leukemic phenotype of CML and related types of leukemia. Our results show that many pathways implicated from the study of established cell lines are not activated when BCR-ABL is first expressed in such progenitor cells, but a subset associated with a selective blockade of cell death mechanisms is activated. (ii) Lymphoid Growth Regulation and Development: A critical regulator of B cell development is Bruton's tyrosine kinase (BTK) identified by our group. Loss of BTK function results in X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. Recently, we have used mass spectroscopy to identify new sites of protein tyrosine phosphorylation within the BTK molecule. Site directed mutations have revealed both positive and negative regulatory phosphorylation control for this kinase. (iii) Metastasis of Prostate Cancer to the Bone Marrow: Prostate cancer is unique in its highly regularized pattern of metastasis to the bone marrow, where it causes an osteoblastic response. One possible therapeutic target is PSCA (for prostate homolog of hematopoietic stem cell antigen). To study such genetic influences we have developed an in vivo prostate reconstitution model which can be experimentally manipulated to regulate specific gene expression and define the stem and progenitor elements of the murine prostate.

Bio:
Dr. Witte is also Professor of Microbiology, Immunology, and Molecular Genetics at the University of California, Los Angeles, where he holds the President's Chair in Developmental Immunology, and Professor of Molecular and Medical Pharmacology at the David Geffen School of Medicine, UCLA; and Founding Director of the Institute for Stem Cell Biology and Medicine recently renamed as the Eli and Edythe Broad Center of Regenerative Medicine nad Stem Cell Research at UCLA. He received his B.S. degree from Cornell University, his M.D. degree from Stanford University, and completed his postdoctoral training at the Massachusetts Institute of Technology. Dr. Witte's honors include the Milken Foundation Award in basic cancer research, the Rosenthal Award of the American Association for Cancer Research, the Dameshek Prize from the American Society of Hematology, the Warren Alpert Foundation Prize, and the de Villiers International Achievement Award from the Leukemia and Lymphoma Society. He is a member of the American Academy of Arts and Sciences, the American Academy of Microbiology, the National Academy of Sciences, and the Institute of Medicine of the NAS. Dr. Witte was named the 2007 UCLA Faculty Research Lecturer. He currently serves on several editorial and advisory boards.

Owen Witte, M.D.

Email Address:
owenw@microbio.ucla.edu

Address:
Laboratory
MRL
Los Angeles, CA 90095
UNITED STATES

Address:
Office
MRL
Los Angeles, CA 90095
UNITED STATES

5-748 MRL
CAMPUS - 166222
CA 90095
UNITED STATES

Phone Number:
(310) 206-0386

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Publications:

Bailey, RC, Kwong, GA Radu, CG, Witte, ON, Heath, JR DNA-Encloded Antibody Libraries: Platform for Multiplexed Cell Sorting and Detection of Genes and Proteins. J Am Chem Soc.. 2007; .

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.

Radu, CG, Shu, CJ, Shelly, SM, Phelps, ME, Witte, ON Positron emission tomography with computed tomography imaging of neuroinflammation in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 2007; 104(6): 1937-42.

Khan, AQ, Sen, G, Guo, S, Witte, ON, Snapper, CM Induction of in vivo anti-polysaccharide immunoglobulin responses to intact Streptococcus pneumoniae is more heavily dependent on Btk-mediated B-cell ceceptor signaling than antiprotein responses. Infect. Immun.. 2006; 74(2): 1419-24.

Lei Q, Jiao J, Xin L, Chang C, Wang S, Gao J, Gleave ME, Witte ON, Liu X, Wu H NKX3.1 Stabilizes p53, Inhibits AKT Activation and Blocks Prostate Cancer Initiation Caused by PTEN Loss. Cancer Cell. 2006; 9(5): 367-78.

Radu CG, Cheng D, Nijagal A, Riedinger M, McLaughlin J, Yang LV, Johnson J, Witte ON Normal Immune Development and Glucocorticoid-induced Thymocyte Apoptosis in Mice Deficient for the T-Cell Death-Associated Gene 8 Receptor. Mol. Cell. Biol. 2006; 26(2): 668-77.

Yang, LV, Radu, CG, Roy, M, Lee, S, McLaughlin, J, Teitell, MA, Iruela-Arispe, ML, Witte, ON 2006. . Epub ahead of print 2006 Dec 4 Vascular abnormalities in mice deficient for the G protein-coupled receptor GPR4 that functions as a pH sensor. Mol Cell Biol.. 2006; 27(4): 1334-47.

Radu CG, Nijagal A, McLaughlin J, Wang L, Witte ON Differential proton sensitivity of related G protein-coupled receptors T cell death-associated gene 8 and G2A expressed in immune cells. Proc Natl Acad Sci U S A. 2005; 102(5): 1632-7.

Wang LR, Yang CG, Bentolila LV, Riedinger LA, Witte ON Lysophosphatidylcholine-induced surface redistribution regulates signaling of the murine G protein-coupled receptor G2A.. Molecular biology of the cell. . 2005; 16(5): 2234-47.

Lee CC, Sui G, Elizarov A, Shu CJ, Shin YS, Dooley AN, Huang J, Stout D, Kolb HC, Witte ON, Satyamurthy N, Heath JR, Phelps ME, Quake SR, Tseng HR Multi-Step Synthesis of a Radiolabeled Imaging Probe Using Integrated Microfluidics. Science. 2005; 310(5755): 1793-6.

Lawson, DA, Xin, L, Lukacs, R, Xu, Q, Cheng, D, Witte, ON Prostate Stem Cells and Prostate Cancer. Cold Spring Harbor Symp. Quant. Biol.. 2005; 70: 187-96.

Kim YJ, Dubey P, Ray P, Gambhir SS, Witte ON Multimodality imaging of lymphocytic migration using lentiviral-based transduction of a tri-fusion reporter gene. Molecular Imaging and Biology. 2004; 6(5): 331-40.

Kharas MG, Deane JA, Wong S, O'Bosky KR, Rosenberg N, Witte ON, Fruman DA Phosphoinositide 3-kinase signaling is essential for ABL oncogene-mediated transformation of B-lineage cells.. Blood. . 2004; 103(11): 4268-75.

Wong S, McLaughlin J, Cheng D, Zhang C, Shokat KM, Witte ON Sole BCR-ABL inhibition is insufficient to eliminate all myeloproliferative disorder cell populations.. Proc Natl Acad Sci U S A. 2004; 101(50): 17456-61.

Yu PW, Tabuchi RS, Kato RM, Astrakhan A, Humblet-Baron S, Kipp K, Chae K, Ellmeier W, Witte ON, Rawlings DJ Sustained correction of B-cell development and function in a murine model of X-linked agammaglobulinemia (XLA) using retroviral-mediated gene transfer.. Blood. . 2004; 104(5): 1281-90.

Radu CG, Yang LV, Riedinger M, Au M, Witte ON T cell chemotaxis to lysophosphatidylcholine through the G2A receptor.. Proc Natl Acad Sci U S A. 2004; 101(1): 245-50.

Wong S, Witte ON The BCR-ABL story: bench to bedside and back. Annual review of immunology. 2004; 22: 247-306.

Wong S, McLaughlin J, Cheng D, Witte ON Cell context-specific effects of the BCR-ABL oncogene monitored in hematopoietic progenitors.. Blood. . 2003; 101(10): 4088-97.

Ferl GZ, Timmerman JM, Witte ON Extending the utility of gene profiling data by bridging microarray platforms.. Proc Natl Acad Sci U S A. 2003; 100(19): 10585-7.

Whyburn LR, Halcomb KE, Contreras CM, Pappu R, Witte ON, Chan AC, Satterthwaite AB Haploinsufficiency of B cell linker protein enhances B cell signaling defects in mice expressing a limiting dosage of Bruton's tyrosine kinase.. International immunology. . 2003; 15(3): 383-92.

Wong S, McLaughlin J, Cheng D, Shannon K, Robb L, Witte ON IL-3 receptor signaling is dispensable for BCR-ABL-induced myeloproliferative disease.. Proc Natl Acad Sci U S A. 2003; 100(20): 11630-5.

Xin L, Ide H, Kim Y, Dubey P, Witte ON In vivo regeneration of murine prostate from dissociated cell populations of postnatal epithelia and urogenital sinus mesenchyme.. Proc Natl Acad Sci U S A. 2003; 100 Suppl 1: 11896-903.

Dubey P, Su H, Adonai N, Du S, Rosato A, Braun J, Gambhir SS, Witte ON Quantitative imaging of the T cell antitumor response by positron-emission tomography. Proc Natl Acad Sci U S A. 2003; 100(3): 1232-7.

Whyburn LR, Halcomb KE, Contreras CM, Lowell CA, Witte ON, Satterthwaite AB Reduced dosage of Bruton's tyrosine kinase uncouples B cell hyperresponsiveness from autoimmunity in lyn-/- mice.. Journal of immunology (Baltimore, Md. : 1950) . 2003; 171(4): 1850-8.

Watabe T, Lin M, Ide H, Donjacour AA, Cunha GR, Witte ON, Reiter RE Growth, regeneration, and tumorigenesis of the prostate activates the PSCA promoter.. Proceedings of the National Academy of Sciences of the United States of America. . 2002; 99(1): 401-6.

Le LQ, Kabarowski JHS, Wong S, Nguyen K, Gambhir SS, Witte ON Positron emission tomography imaging analysis of G2A as a negative modifier of lymphoid leukemogenesis initiated by the BCR-ABL oncogene. Cancer Cell. 2002; 1(4): 381-391.