Faculty > Frisch

Steven M. Frisch, Ph.D.

Professor

PhD: University of California, Berkeley
Postdoctoral Training: Center for Cancer Research, MIT
Joined the faculty: 2004
Affiliations: MBR Cancer Center
Teaching: BMS 705, CCB 700, CCMD 793L, CCMD 793M, CCMD 730

Office: 2836 HSS
Phone: (304) 293-2980
Fax: (304) 293-4667
Email: sfrisch@hsc.wvu.edu

Research Interests:

Anoikis. Our laboratory discovered the phenomenon of "anoikis” - apoptosis that is triggered by detachment of cells from their matrix or attachment to an inappropriate matrix. Anoikis safeguards against the circulation and colonization of cells released from normal epithelial tissues or from tumors. It is therefore critical for preventing metastasis. Anoikis conceptually bridges the cell adhesion/signal transduction/cytoskeleton and the apoptosis fields; its fundamental mechanisms remain to be discovered. The mechanism of anoikis and the development of novel cancer therapeutics based on this mechanism is a major focus of the laboratory.

EMT and cancer stem cells. The oncogenic epithelial-to-mesenchymal transition (EMT) has recently been connected with the “cancer stem cell” phenotype, i.e., a subset of tumor cells that express high levels of CD44, are exceptionally tumorigenic, and resistant to chemotherapy (probably giving rise to tumor recurrence after chemotherapy).

Our lab is investigating several aspects of EMT:

  1. The role CD44 in programming EMT, anoikis-resistance and the cancer stem cell phenotype;
  2. The role of the transcription factor C-terminal Binding Protein (CtBP) in the maintenance of EMT, and drug discovery based on this target;
  3. Mechanisms by which the epithelial cell adhesion molecule, E-cadherin, regulates cellular sensitivity to anoikis.

Caspase-8 as a cell migration/tumor invasion gene. Caspase-8 is widely known for its proapoptotic role, but our findings reveal that it is also a cell migration, cell adhesion and tumor cell invasion factor. It appears to function partly by activating the calpain family of proteases and partly by binding to and activating the p85 subunit of PI3-kinase, leading to increased activation of Rac and ensuing migration. These mechanisms are being investigated in more detail and a mouse model to test the hypothesis that caspase-8 is a pro-metastatic gene is being constructed presently.

Lab Website:

Frisch Lab

Publications:

Frisch, SM, Schaller, M, Cieply, B. Mechanisms that link the oncogenic epithelial-mesenchymal transition to suppression of anoikis. J. Cell Sci Jan 1;126(Pt 1):21-9. doi: 10.1242/jcs.120907

Park,S, Riley IV, P, Frisch SM. Regulation of anoikis by Deleted in Breast Cancer-1 (DBC1) through NF-kB. Apoptosis April 16 Epub ahead of print). PMID: 23588592

Cieply B, Riley IV P, Pifer PM, Widmeyer J, Addison JB, Ivanov AV, Denvir J, Frisch SM. Suppression of the epithelial-mesenchymal transition by Grainyhead-like-2. Cancer Research 72: 2440-2453, 2012

Frisch SM, Schaller M, Cieply, B. Mechanisms that link the oncogenic epithelial-mesenchymal transition to suppression of anoikis. J. Cell Sci. 126:22-29, 2013

Cieply B, Riley P, Pifer P, Widmeyer J, Addison JB, Ivanov AV, Denvir J, Frisch SM. Suppression of the epithelial-mesenchymal transition by grainyhead-like-2. Cancer Res.  72:  2440-2453, 2012

Kumar S, Park SH, Cieply B, Schupp J, Killiam E, Zhang F, Rimm DL, Frisch SM. A pathway for the control of anoikis sensitivity by E-cadherin and epithelial-to-mesenchymal transition. Mol Cell Biol. 2011 Oct; 31 (19):4036-51. Epub 2011 Jul 11.