Research Topics

 Project 1:  Characterizing the interaction of the tumor suppressors NORE1A and PMLIV

Ras is a potent oncogene that experiences activating mutations in numerous cancers, resulting in uncontrolled cell growth and proliferation. However, Ras also has the contradictory ability to promote apoptosis and to activate cellular senescence. NORE1A is a member of the RASSF family of tumor suppressors that can bind directly to Ras to promote apoptosis. NORE1A does so by acting as a scaffolding molecule, linking Ras to pro-apoptotic and growth inhibitory pathways. Our laboratory has identified NORE1A as a critical mediator of Ras-induced senescence. NORE1A’s mechanism of action, however, remains unclear. PMLIV is an isoform of the promyelocytic leukemia (PML) protein and has been implicated in Ras-mediated senescence and in the control of p53. Our laboratory has found that NORE1A and PMLIV co-localize within the cell and that the two form an endogenous complex in hepatocellular carcinoma tumor samples. NORE1A may thus serve as the link between Ras and PMLIV, and the interaction of NORE1A and PMLIV may play a key role in Ras-mediated senescence.

 Project 2:  RASSF6 in metastatic melanoma

RASSF proteins are a family of pro-apoptotic tumor suppressors. Some members of this family exhibit frequent epigenetic inactivation during tumorigenesis. Brain metastasis is a major contributor to cancer mortality, yet the genetic changes underlying the development of this capacity remain poorly understood. We have identified RASSF6 as the RASSF family member with the highest frequency of epigenetic inactivation in melanoma and melanoma brain metastases. This project seeks to determine if epigenetic inactivation of RASSF6 plays a role in melanoma development and contributes to melanoma brain metastases.   

 Thesis Committee

1. Geoff Clark, PhD
2. Ronald Gregg, PhD
3. Carolyn Klinge, PhD
4. Robert Mitchell, PhD
5. Christine Schaner Tooley, PhD

Posters Presented

1. RASSF6 Modulates Melanoma Metastasis. Jessica N. Mezzanotte, Farida Latif, M. Lee Schmidt, Howard Donninger, Geoffrey J. Clark. South Central MD/PhD Conference (Nov. 2013). Columbus, Ohio.
2. RASSF6 Modulates Melanoma Metastasis. Jessica N. Mezzanotte, Farida Latif, M. Lee Schmidt, Howard Donninger, Geoffrey J. Clark.  Research! Louisville (Sept. 2011). Louisville, KY
3. Lung Cancer Cells Require Pyruvate Carboxylase For Anaplerotic Flux Into the Krebs Cycle and for Anchorage-Independent Growth. Jessica N. Mezzanotte, Amber Macpherson, Amy Clem, Neil E. Crittenden, Deanna Siow, Sucheta Telang, Brian Clem and Jason Chesney. Research! Louisville (Sept. 2010). Louisville, KY.
4. Characterization of mid-gut proteases in social aphids. Jessica N. Mezzanotte and Patrick Abbot. Vanderbilt Undergraduate Summer Research Program Symposium (Sept. 2009). Nashville, TN.

 Conferences Attended

 South Central MD/PhD Conference (Nov. 2013). Columbus, Ohio.

 Professional Memberships

• American Physician Scientists Association