Our Faculty > Michael J. Weber

Michael J. Weber

Michael J. Weber

Education

  • Postdoc, University of California, Berkeley, CA
  • BS, Haverford College, Haverford, PA
  • PhD, University of California, San Diego, CA

Primary Appointment

  • Professor, Microbiology, Immunology, and Cancer Biology

Contact

Research Interest(s)

Signal Transducing Kinases in Cancer

Research Description

Cells continually make decisions about their fate: growth, death or differentiation. These decisions frequently are determined by signal transduction cascades of small GTP-binding proteins and protein kinases, which are activated in response to extracellular signals. Our laboratory utilizes tools of cell biology, protein chemistry and molecular biology to understand how signal transduction controls cell growth and apoptosis, how these controls are altered in cancer, and how this information can be used to improve cancer treatment.
MAP kinases: regulation and function.
MAP Kinase cascades are among the most thoroughly studied of signal transduction systems, and have been shown to participate in a diverse array of cellular programs including cell differentiation, cell movement, cell division and cell death. They typically are organized in a three-kinase architecture consisting of a MAP Kinase (MAPK), a MAP Kinase activator (MEK) and a MEK activator (MEKK). Transmission of signals is achieved by sequential phosphorylation and activation of the components specific to a respective cascade. In mammalian systems five distinguishable MAP Kinase modules have been identified so far. These include the canonical ERK1/2 cascade that preferentially regulates cell growth and differentiation. Increased understanding of the ways these enzymes are regulated, targeted intracellularly and linked with other signaling pathways will enhance our insight into the regulatory networks that control cell behavior and provide clues as to how to exploit these as targets for therapy.
Signal transduction in human cancer.
Cancers undergo progressive changes that increase their malignant potential and thereby render them less susceptible to treatment. Analysis of the cellular signaling mechanisms that link the outside of the cancer cell to receptors and intracellular signal transduction cascades will provide insight into prevention, detection, and treatment strategies for cancer. Much of our recent efforts have been on elucidating the ways that redundant and compensatory signaling pathways neutralize the effects of targeted therapies. We currently are using cell and xenograft cancer systems in melanoma, bladder, prostate and head and neck cancers, each of which provides unique opportunities to match knowledge about signaling with potential therapeutic interventions.

Selected Publications

  • Gioeli D, Black B, Gordon V, Spencer A, Kesler C, Eblen S, Paschal B, Weber M. Stress Kinase Signaling Regulates Androgen Receptor Phosphorylation, Transcription, and Localization. Molecular Endocrinology. 20(3): 503-515.
  • Wu Z, Conaway M, Gioeli D, Weber M, Theodorescu D. Conditional expression of PTEN alters the androgen responsiveness of prostate cancer cells. Prostate. 66(10): 1114-23.
  • Kraus S, Gioeli D, Vomastek T, Gordon V, Weber M. Receptor for activated C kinase 1 (RACK1) and Src regulate the tyrosine phosphorylation and function of the androgen receptor. Cancer Res. 66(22): 11047-54.
  • Kesler C, Gioeli D, Conaway M, Weber M, Paschal B. Subcellular localization modulates activation function 1 domain phosphorylation in the androgen receptor. Mol Endocrinol. 21(9): 2071-84.
  • Bigler D, Gioeli D, Conaway M, Weber M, Theodorescu D. Rap2 regulates androgen sensitivity in human prostate cancer cells. Prostate. 67(14): 1590-9.
  • Vomastek T, Iwanicki M, Schaeffer H, Tarcsafalvi A, Parsons J, Weber M. RACK1 targets the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway to link integrin engagement with focal adhesion disassembly and cell motility. Mol Cell Biol. 27(23): 8296-305. PMCID: PMC2169169
  • Wu Z, Gioeli D, Conaway M, Weber M, Theodorescu D. Restoration of PTEN expression alters the sensitivity of prostate cancer cells to EGFR inhibitors. Prostate. 2008;68(9): 935-44. PMCID: PMC2748221
  • Vomastek T, Iwanicki M, Burack W, Tiwari D, Kumar D, Parsons J, Weber M, Nandicoori V. Extracellular signal-regulated kinase 2 (ERK2) phosphorylation sites and docking domain on the nuclear pore complex protein Tpr cooperatively regulate ERK2-Tpr interaction. Mol Cell Biol. 2008;28(22): 6954-66. PMCID: PMC2573295
  • DaSilva J, Gioeli D, Weber M, Parsons S. The neuroendocrine-derived peptide parathyroid hormone-related protein promotes prostate cancer cell growth by stabilizing the androgen receptor. Cancer Res. 69(18): 7402-11. PMCID: PMC2803023
  • Thammasitboon S, Rosen D, Lutfi R, Ely B, Weber M, Hilvers P, Gustafson R. An institutional experience with epidural analgesia in children and young adults undergoing cardiac surgery. Paediatric anaesthesia. 2010;20(8): 720-6. PMID: 20670235
  • Sica D, White W, Weber M, Bakris G, Perez A, Cao C, Handley A, Kupfer S. Comparison of the novel angiotensin II receptor blocker azilsartan medoxomil vs valsartan by ambulatory blood pressure monitoring. Journal of clinical hypertension (Greenwich, Conn.). 2011;13(7): 467-72. PMID: 21762358
  • Gioeli D, Wunderlich W, Sebolt-Leopold J, Bekiranov S, Wulfkuhle J, Petricoin E, Conaway M, Weber M. Compensatory pathways induced by MEK inhibition are effective drug targets for combination therapy against castration-resistant prostate cancer. Molecular cancer therapeutics. 2011;10(9): 1581-90. PMID: 21712477 | PMCID: PMC3315368
  • Gioeli D, Wunderlich W, Sebolt-Leopold J, Bekiranov S, Wulfkuhle J, Petricoin 3, Conaway M, Weber M. Compensatory Pathways Induced by MEK Inhibition Are Effective Drug Targets for Combination Therapy against Castration-Resistant Prostate Cancer. Mol Cancer Ther. .
  • Gioeli D, Wunderlich W, Sebolt-Leopold J, Bekiranov S, Wulfkuhle J, Petricoin 3, Conaway M, Weber M. Compensatory Pathways Induced by MEK Inhibition Are Effective Drug Targets for Combination Therapy against Castration-Resistant Prostate Cancer. Mol Cancer Ther. .
  • Gioeli D, Wunderlich W, Sebolt-Leopold J, Bekiranov S, Wulfkuhle J, Petricoin 3, Conaway M, Weber M. Compensatory Pathways Induced by MEK Inhibition Are Effective Drug Targets for Combination Therapy against Castration-Resistant Prostate Cancer. Mol Cancer Ther. .
  • Weber M, Stutzman R, Mines M, Eiseman A, Wroblewski K, Ryan D, Sia R, Bower K. Residency training in refractive surgery. Journal of cataract and refractive surgery. 2012;38(11): 1962-9. PMID: 23079312
  • Sica D, Bakris G, White W, Weber M, Cushman W, Huang P, Roberts A, Kupfer S. Blood pressure-lowering efficacy of the fixed-dose combination of azilsartan medoxomil and chlorthalidone: a factorial study. Journal of clinical hypertension (Greenwich, Conn.). 2012;14(5): 284-92. PMID: 22533654
  • Roller D, Axelrod M, Capaldo B, Jensen K, Mackey A, Weber M, Gioeli D. Synthetic lethal screening with small molecule inhibitors provides a pathway to rational combination therapies for melanoma. Molecular cancer therapeutics. 2012. PMID: 22962324 | PMCID: NIHMS405900