Owen Witte

Last updated
Owen Witte
Born (1949-05-17) May 17, 1949 (age 74)
Brooklyn, New York, US
Alma materCornell University (B.S.) Stanford University School of Medicine (M.D.)
Scientific career
InstitutionsStanford University
MIT
University of California, Los Angeles
Howard Hughes Medical Institute
Websitewww.stemcell.ucla.edu/member/witte

Owen Witte (born May 17, 1949) is an American physician-scientist at the University of California, Los Angeles. He is a University Professor of microbiology, immunology and molecular genetics in the David Geffen School of Medicine at UCLA, founding director emeritus of the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, and the UC Regents’ David Saxon Presidential Chair in developmental immunology (1989–present). [1] Witte is also a Howard Hughes Medical Institute investigator (1986–2016) and a member of the President's Cancer Panel (2012 to 2016), [2] the National Academy of Sciences, the National Academy of Medicine, the American Academy of Arts and Sciences, and the Cancer Research Academy of the AACR. He serves on numerous editorial boards and scientific advisory boards for academic centers and biotechnology companies.

Contents

Witte should be recognized for multiple seminal contributions over the last 50 years impacting our understanding of human leukemias, immune disorders and epithelial cancers, which have defined new targets for attack that have foreshadowed and strongly influenced the development of new therapies that have changed medical practice and patient outcomes. His discovery of the tyrosine kinase activity in the ABL1 protein [3] and the demonstration of the BCR-ABL oncoproteins in leukemias [4] was one of the preclinical discoveries that led to the development of Gleevec, the first targeted therapy for chronic myelogenous leukemia. [1]

Witte also co-discovered the gene for Bruton's tyrosine kinase, [5] a protein essential for normal B-lymphocyte development that, when mutated, causes the onset of X-linked agammaglobulinemia. [6] This finding stimulated the creation of new targeted therapies like Ibrutinib that have transformed treatment for CLL, B cell lymphomas, multiple myeloma and certain autoimmune diseases. [1]

His current research focuses on characterizing the stem cells for epithelial cancers of the prostate and other organs in order to define new and more targeted therapies. [7] [8] Using tissue modeling techniques, Witte discovered the prostate stem cell antigen that is up-regulated in prostate cancer, [9] identified the human prostate stem cell population [10] and determined that the protein N-Myc, which is produced by the gene MYCN, leads to the development of aggressive neuroendocrine prostate cancer tumors. [11] Recent striking observations using a human epithelial tissue recombination/transformation system have shown that prostate and other tissues can be driven to an adenocarcinoma state by defined oncogenic signaling, and further trans-differentiated by epigenetic control to highly aggressive small cell carcinoma with neuroendocrine features — defining new immune targets for therapy under active investigation.

Education

Witte earned his B.S. degree in microbiology from Cornell University in 1971. He earned his M.D. degree from Stanford University in 1976, specializing in molecular virology, immunology and medicine.

He completed his predoctoral fellowship in the laboratory of Irving Weissman (Stanford University; 1971 to 1976) and his postdoctoral fellowship in the laboratory of Nobel laureate Dr. David Baltimore (MIT; 1976 to 1980). [1]

Awards

Related Research Articles

<span class="mw-page-title-main">Tyrosine kinase</span> Class hi residues

A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions.

<span class="mw-page-title-main">Philadelphia chromosome</span> Genetic abnormality in leukemia cancer cells

The Philadelphia chromosome or Philadelphia translocation (Ph) is a specific genetic abnormality in chromosome 22 of leukemia cancer cells. This chromosome is defective and unusually short because of reciprocal translocation, t(9;22)(q34;q11), of genetic material between chromosome 9 and chromosome 22, and contains a fusion gene called BCR-ABL1. This gene is the ABL1 gene of chromosome 9 juxtaposed onto the breakpoint cluster region BCR gene of chromosome 22, coding for a hybrid protein: a tyrosine kinase signaling protein that is "always on", causing the cell to divide uncontrollably by interrupting the stability of the genome and impairing various signaling pathways governing the cell cycle.

<span class="mw-page-title-main">CD44</span> Cell-surface glycoprotein

The CD44 antigen is a cell-surface glycoprotein involved in cell–cell interactions, cell adhesion and migration. In humans, the CD44 antigen is encoded by the CD44 gene on chromosome 11. CD44 has been referred to as HCAM, Pgp-1, Hermes antigen, lymphocyte homing receptor, ECM-III, and HUTCH-1.

<span class="mw-page-title-main">Lck</span> Lymphocyte protein

Lck is a 56 kDa protein that is found inside specialized cells of the immune system called lymphocytes. The Lck is a member of Src kinase family (SFK) and is important for the activation of T-cell receptor (TCR) signaling in both naive T cells and effector T cells. The role of Lck is less prominent in the activation or in the maintenance of memory CD8 T cells in comparison to CD4 T cells. In addition, the constitutive activity of the mouse Lck homolog varies among memory T cell subsets. It seems that in mice, in the effector memory T cell (TEM) population, more than 50% of Lck is present in a constitutively active conformation, whereas less than 20% of Lck is present as active form in central memory T cells. These differences are due to differential regulation by SH2 domain–containing phosphatase-1 (Shp-1) and C-terminal Src kinase.

<span class="mw-page-title-main">Bruton's tyrosine kinase</span> Kinase that plays a crucial role in B cell development.

Bruton's tyrosine kinase, also known as tyrosine-protein kinase BTK, is a tyrosine kinase that is encoded by the BTK gene in humans. BTK plays a crucial role in B cell development.

<span class="mw-page-title-main">Tyrosine-protein kinase SYK</span>

Tyrosine-protein kinase SYK, also known as spleen tyrosine kinase, is an enzyme which in humans is encoded by the SYK gene.

<span class="mw-page-title-main">CD19</span> Biomarker for B cell lineage

B-lymphocyte antigen CD19, also known as CD19 molecule, B-Lymphocyte Surface Antigen B4, T-Cell Surface Antigen Leu-12 and CVID3 is a transmembrane protein that in humans is encoded by the gene CD19. In humans, CD19 is expressed in all B lineage cells. Contrary to some early doubts, human plasma cells do express CD19, as confirmed by others. CD19 plays two major roles in human B cells: on the one hand, it acts as an adaptor protein to recruit cytoplasmic signaling proteins to the membrane; on the other, it works within the CD19/CD21 complex to decrease the threshold for B cell receptor signaling pathways. Due to its presence on all B cells, it is a biomarker for B lymphocyte development, lymphoma diagnosis and can be utilized as a target for leukemia immunotherapies.

<span class="mw-page-title-main">KIT (gene)</span> Mammalian protein and protein-coding gene

Proto-oncogene c-KIT is the gene encoding the receptor tyrosine kinase protein known as tyrosine-protein kinase KIT, CD117 or mast/stem cell growth factor receptor (SCFR). Multiple transcript variants encoding different isoforms have been found for this gene. KIT was first described by the German biochemist Axel Ullrich in 1987 as the cellular homolog of the feline sarcoma viral oncogene v-kit.

<span class="mw-page-title-main">CD135</span> Protein-coding gene in the species Homo sapiens

Cluster of differentiation antigen 135 (CD135) also known as fms like tyrosine kinase 3, receptor-type tyrosine-protein kinase FLT3, or fetal liver kinase-2 (Flk2) is a protein that in humans is encoded by the FLT3 gene. FLT3 is a cytokine receptor which belongs to the receptor tyrosine kinase class III. CD135 is the receptor for the cytokine Flt3 ligand (FLT3L).

<span class="mw-page-title-main">Janus kinase 3</span> Mammalian protein found in Homo sapiens

Tyrosine-protein kinase JAK3 is a tyrosine kinase enzyme that in humans is encoded by the JAK3 gene.

<span class="mw-page-title-main">Alexander Levitzki</span> Israeli biochemist

Alexander Levitzki is an Israeli biochemist who is a professor of biochemistry at the Alexander Silberman Institute of Life Sciences, the Hebrew University of Jerusalem.

<span class="mw-page-title-main">Proto-oncogene tyrosine-protein kinase Src</span> Mammalian protein found in Homo sapiens

Proto-oncogene tyrosine-protein kinase Src, also known as proto-oncogene c-Src, or simply c-Src, is a non-receptor tyrosine kinase protein that in humans is encoded by the SRC gene. It belongs to a family of Src family kinases and is similar to the v-Src gene of Rous sarcoma virus. It includes an SH2 domain, an SH3 domain and a tyrosine kinase domain. Two transcript variants encoding the same protein have been found for this gene.

<span class="mw-page-title-main">Colony stimulating factor 1 receptor</span> Protein found in humans

Colony stimulating factor 1 receptor (CSF1R), also known as macrophage colony-stimulating factor receptor (M-CSFR), and CD115, is a cell-surface protein encoded by the human CSF1R gene. CSF1R is a receptor that can be activated by two ligands: colony stimulating factor 1 (CSF-1) and interleukin-34 (IL-34). CSF1R is highly expressed in myeloid cells, and CSF1R signaling is necessary for the survival, proliferation, and differentiation of many myeloid cell types in vivo and in vitro. CSF1R signaling is involved in many diseases and is targeted in therapies for cancer, neurodegeneration, and inflammatory bone diseases.

<span class="mw-page-title-main">Tyrosine-protein kinase Fes/Fps</span> Human protein and coding gene

Tyrosine-protein kinase Fes/Fps also known as proto-oncogene c-Fes/Fps is an enzyme that in humans is encoded by the FES gene. FES was originally cloned as a retroviral oncogene from feline (v-FES) and avian (v-FPS) sarcomas. This triggered the subsequent identification and cloning of the cellular FES (c-FES) genes in birds and mammals.

<span class="mw-page-title-main">PIM1</span> Protein-coding gene in the species Homo sapiens

Proto-oncogene serine/threonine-protein kinase Pim-1 is an enzyme that in humans is encoded by the PIM1 gene.

<span class="mw-page-title-main">AXL receptor tyrosine kinase</span> Protein-coding gene in the species Homo sapiens

Tyrosine-protein kinase receptor UFO is an enzyme that in humans is encoded by the AXL gene. The gene was initially designated as UFO, in allusion to the unidentified function of this protein. However, in the years since its discovery, research into AXL's expression profile and mechanism has made it an increasingly attractive target, especially for cancer therapeutics. In recent years, AXL has emerged as a key facilitator of immune escape and drug-resistance by cancer cells, leading to aggressive and metastatic cancers.

<span class="mw-page-title-main">TEC (gene)</span> Human gene

Tyrosine-protein kinase Tec is a tyrosine kinase that in humans is encoded by the TEC gene. Tec kinase is expressed in hematopoietic, liver, and kidney cells and plays an important role in T-helper cell processes. Tec kinase is the name-giving member of the Tec kinase family, a family of non-receptor protein-tyrosine kinases.

Interleukin-28 receptor is a type II cytokine receptor found largely in epithelial cells. It binds type 3 interferons, interleukin-28 A, Interleukin-28B, interleukin 29 and interferon lambda 4. It consists of an α chain and shares a common β subunit with the interleukin-10 receptor. Binding to the interleukin-28 receptor, which is restricted to select cell types, is important for fighting infection. Binding of the type 3 interferons to the receptor results in activation of the JAK/STAT signaling pathway.

<span class="mw-page-title-main">ROR1</span> Protein-coding gene in the species Homo sapiens

Tyrosine-protein kinase transmembrane receptor ROR1, also known as neurotrophic tyrosine kinase, receptor-related 1 (NTRKR1), is an enzyme that in humans is encoded by the ROR1 gene. ROR1 is a member of the receptor tyrosine kinase-like orphan receptor (ROR) family.

<span class="mw-page-title-main">Anthony R. Hunter</span> British-American biologist (born 1943)

Anthony Rex Hunter is a British-American biologist who is a professor of biology at the Salk Institute for Biological Studies and the University of California San Diego. His research publications list his name as Tony Hunter.

References

  1. 1 2 3 4 5 Vogt-James, Mirabai (August 3, 2015). "The 2015 AQACR Clowes Memorial Award for Outstanding Achievement in Basic Cancer Research". Cancer Immunology Research. 3 (8): 846–848. doi: 10.1158/2326-6066.CIR-15-0142 . PMID   26242762.
  2. ↑ "President's Cancer Panel".
  3. ↑ Witte ON, Dasgupta A, Baltimore D (February 28, 1980). "Abelson murine leukemia virus protein is phosphorylated in vitro to form phosphotyrosine". Nature. 283 (5750): 826–831. Bibcode:1980Natur.283..826W. doi:10.1038/283826a0. PMID   6244493. S2CID   4239008.
  4. ↑ Konopka JB, Watanabe SM, Witte ON (July 1984). "An alteration of the human c-abl protein in K562 leukemia cells unmasks associated tyrosine kinase activity" (PDF). Cell. 37 (3): 1035–42. doi:10.1016/0092-8674(84)90438-0. PMID   6204766. S2CID   34525263.
  5. ↑ Tsukada S; Saffran DC; Rawlings DJ; Parolini O; Allen RC; Klisak I; et al. (January 29, 1993). "Deficient expression of a B-cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia". Cell. 72 (2): 279–90. doi:10.1016/0092-8674(93)90667-f. PMID   8425221. S2CID   32339052.
  6. ↑ Rawlings DJ; Scharenberg AM; Park H; Wahl MI; Lin S; Kato RM; et al. (February 9, 1996). "Activation of Btk by a phosphorylation mechanism initiated by src family kinases". Science. 271 (5250): 822–5. Bibcode:1996Sci...271..822R. doi:10.1126/science.271.5250.822. PMID   8629002. S2CID   42666246.
  7. ↑ "SU2C Scientific Research Teams, Owen N. Witte, M.D." Stand Up To Cancer.
  8. 1 2 "Owen N. Witte, MD | Class of 2014". American Association for Cancer Research.
  9. ↑ Reiter, R.E.; Gu, Z.; Watabe, T.; Thomas, G.; Szigeti, K.; Davis, E.; Wahl, M.; Nisitani, S.; Yamashiro, J.; Le Beau, M.M.; Loda, M.; Witte, O.N. (February 17, 1998). "Prostate stem cell antigen: A cell surface marker overexpressed in prostate cancer". Proceedings of the National Academy of Sciences. 95 (4): 1735–40. Bibcode:1998PNAS...95.1735R. doi: 10.1073/pnas.95.4.1735 . PMC   19171 . PMID   9465086.
  10. ↑ Goldstein, A.S.; Huang, J.; Guo, C.; Garraway, I.P.; Witte, O.N. (July 30, 2010). "Identification of a cell-of-origin for human prostate cancer". Science. 329 (5991): 568–71. Bibcode:2010Sci...329..568G. doi:10.1126/science.1189992. PMC   2917982 . PMID   20671189.
  11. ↑ Lee JK, Phillips JW, Smith BA, Park JW, Stoyanova T, Clark PM, Baertsch R, Sokolov A, Meyerowitz JG, Mathis C, Cheng D, Stuart JM, Gustafson WC, Huang J, Witte ON (April 11, 2016). "N-Myc drives small cell neuroendocrine carcinoma initiated from human prostate epithelial cells". Cancer Cell. 29 (4): 536–547. doi:10.1016/j.ccell.2016.03.001. PMC   4829466 . PMID   27050099.
  12. ↑ "American Association for Cancer Research". AACR.org.
  13. ↑ "The 2014 Rowley Prize is awarded to Dr Owen N. Witte". cml-foundation.org.
  14. ↑ Vogt-James, Mirabai. "UC regents appoint Dr. Owen Witte University Professor". UCLA Newsroom.
  15. ↑ "AACR Announces 2024 Scientific Achievement Award Recipients". American Association for Cancer Research (AACR). Retrieved 2024-03-01.
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