- Biomedical Sciences Graduate Program | Michael J. Weber

Michael J. Weber


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

Primary Appointment

  • Professor, Microbiology, Immunology, and Cancer Biology


Research Interest(s)

Targeting Cell Signaling for Cancer Therapy.

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 and lead to drug resistance. We currently are using cell and xenograft cancer systems in melanoma, as well as patient samples in B-Cell malignancies each of which provides unique opportunities to match knowledge about signaling with potential therapeutic interventions.

Selected Publications

  • Axelrod M, Gordon V, Conaway M, Tarcsafalvi A, Neitzke D, Gioeli D, Weber M. Combinatorial drug screening identifies compensatory pathway interactions and adaptive resistance mechanisms. Oncotarget. 2013;4(4): 622-35. PMID: 23599172 | PMCID: PMC3720609
  • Axelrod M, Ou Z, Brett L, Zhang L, Lopez E, Tamayo A, Gordon V, Ford R, Williams M, Pham L, Weber M, Wang M. Combinatorial drug screening identifies synergistic co-targeting of Bruton's tyrosine kinase and the proteasome in mantle cell lymphoma. Leukemia. 2013. PMID: 23979520 | PMCID: PMC3918872
  • Slingluff C, Petroni G, Molhoek K, Brautigan D, Chianese-Bullock K, Shada A, Smolkin M, Olson W, Gaucher A, Chase C, Grosh W, Weiss G, Wagenseller A, Olszanski A, Martin L, Shea S, Erdag G, Ram P, Gershenwald J, Weber M. Clinical activity and safety of combination therapy with temsirolimus and bevacizumab for advanced melanoma: a phase II trial (CTEP 7190/Mel47). Clinical cancer research : an official journal of the American Association for Cancer Research. 2013;19(13): 3611-20. PMID: 23620404 | PMCID: PMC3700572
  • 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
  • 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
  • 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 research. 2009;69(18): 7402-11. PMID: 19706771 | PMCID: PMC2803023
  • 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. Molecular and cellular biology. 2008;28(22): 6954-66. PMID: 18794356 | PMCID: PMC2573295
  • Wu Z, Gioeli D, Conaway M, Weber M, Theodorescu D. Restoration of PTEN expression alters the sensitivity of prostate cancer cells to EGFR inhibitors. The Prostate. 2008;68(9): 935-44. PMID: 18386291 | PMCID: PMC2748221
  • 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. Molecular and cellular biology. 2007;27(23): 8296-305. PMID: 17908799 | PMCID: PMC2169169