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President's Chair in Developmental Immunology,
Microbiology, Immunology & Molecular Genetics
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Distinguished Professor,
Microbiology, Immunology & Molecular Genetics
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Professor,
Molecular & Medical Pharmacology
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Member,
California NanoSystems Institute
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Education: |
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Degrees:
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B.S., Cornell University, 1971
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M.D.:
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1976 Stanford University School of Medicine, Molecular Virology, Immunology and Medicine
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Fellowships:
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Center for Cancer Research, MIT, Postdoctoral Fellow (1976-1980)
Stanford University School of Medicine, Predoctoral Fellow (1971-1976)
1997 American Academy of Microbiology , Fellow, American Academy of Microbiology
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Certifications: |
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Professional Societies:
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American Academy of Arts and Sciences, Fellow (1996)
Institute of Medicine, Member (2003)
National Academy of Sciences, Member (1997)
1990 Member, American Society for Clinical Investigation (1990)
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Contact Information:
| Laboratory Address: |
Laboratory
MRL
Los Angeles, CA 90095
UNITED STATES
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| Work Address: |
Office
MRL
Los Angeles, CA 90095
UNITED STATES
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| Work Address: |
5-748 MRL
CAMPUS - 166222
CA 90095
UNITED STATES
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Work Phone Number:
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(310) 206-0386
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Research Interests:
My laboratory is concerned with the interrelated problems of cell growth regulation and 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. We are also interested in understanding the regulation of lymphocyte growth in disease states and during immune responses. We 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, we identified a G protein-coupled receptor family which regulates inflammatory responses and autoimmunity and are studying its mechanisms of action. We are using PET and other imaging modalities to study lymphocyte movement during the immune response to tumor antigens.
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Technical Research Interest:
Research involves the interrelated problems of cell growth
regulation, differentiation and understanding function of
oncogenes found in human leukemias and epithelial cancers.
This includes the Bcr-Abl tyrosine kinase important in human
chronic myelogenous leukemia and understanding regulation
of lymphocyte growth in disease states during immune
responses. We discovered gene defects in primary immunodeficiency X-linked agammaglobulinemia are a single gene called
Bruton's tyrosine kinase and now study its mode of action.
We identified a G protein-coupled receptor family which regulates
inflammatory responses and autoimmunity and study
mechanisms of action. We use 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. We use surface markers to fractionate normal murine prostate cell populations in an
attempt to define active stem cell populations and recently
developed dissociated cell reconstitution systems in which
prostate epithelial stem and progenitor cells can be induced to
form glandular tissue structures.
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Additional Information:
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.
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Lo, R. Nazarian, R. Zong, Y. Ribas, A. Witte, O. , Autophagy regulates melanoma glycogen synthase kinase-3-dependent survival, Journal of Investigative Dermatology, 2009, 129, S140-S140.
Lukacs, R. U. Lawson, D. A. Xin, L. Zong, Y. Garraway, I. Goldstein, A. S. Memarzadeh, S. Witte, O. N. , Epithelial Stem Cells of the Prostate and Their Role in Cancer Progression, Cold Spring Harb Symp Quant Biol, 2008, volume (number), pages.
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.
McLaughlin, J. Cheng, D. Singer, O. Lukacs, R. U. Radu, C. G. Verma, I. M. Witte, O. N. , Sustained suppression of Bcr-Abl-driven lymphoid leukemia by microRNA mimics, Proc Natl Acad Sci U S A, 2007, 104 ( 51), 20501-6.
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.
Witte ON, Kabarowski JH, Xu Y, Le LQ, Zhu K, Retraction, Science, 2005, 307 (5707), 206.
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, 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.
Satterthwaite, A. B. Willis, F. Kanchanastit, P. Fruman, D. Cantley, L. C. Helgason, C. D. Humphries, R. K. Lowell, C. A. Simon, M. Leitges, M. Tarakhovsky, A. Tedder, T. F. Lesche, R. Wu, H. Witte, O. N. , A sensitized genetic system for the analysis of murine B lymphocyte signal transduction pathways dependent on Bruton's tyrosine kinase, Proc Natl Acad Sci U S A, 2000, 97 ( 12), 6687-92.
Kabarowski, J. H. Feramisco, J. D. Le, L. Q. Gu, J. L. Luoh, S. W. Simon, M. I. Witte, O. N. , Direct genetic demonstration of G alpha 13 coupling to the orphan G protein-coupled receptor G2A leading to RhoA-dependent actin rearrangement, Proc Natl Acad Sci U S A, 2000, 97 ( 22), 12109-14.
Nisitani, S. Satterthwaite, A. B. Akashi, K. Weissman, I. L. Witte, O. N. Wahl, M. I. , Posttranscriptional regulation of Bruton's tyrosine kinase expression in antigen receptor-stimulated splenic B cells, Proc Natl Acad Sci U S A, 2000, 97 ( 6), 2737-42.
Era, T. Witte, O. N. , Regulated expression of P210 Bcr-Abl during embryonic stem cell differentiation stimulates multipotential progenitor expansion and myeloid cell fate, Proc Natl Acad Sci U S A, 2000, 97 ( 4), 1737-42.
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