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Fesik Lab

OLIVIA W. ROSSANESE Ph.D.

 

 
Research Assistant Professor of Biochemistry
 

Office:      802-C RRB

Phone:     615-936-8708

Email:      olivia.rossanese@vanderbilt.edu

 

Cell/Cancer Biology

Olivia W. Rossanese, Ph.D. is a Research Assistant Professor of Biochemistry and a Cancer Cell Biology Group Leader for the Fesik Lab. Her group develops and conducts biochemical and cell-based assays to drive SAR and support cancer drug discovery.  Cell Biology group is also developing and running plate-based assays to measure cell proliferation and viability, anchorage-independent growth, kinase activity, migration, apoptosis, and signaling, using a number of readouts and detection systems. Recent examples of successful assays include the RPA70-ATRIP fluorescence polarization anisotropy assay that is read on the Perkin Elmer Envision, a kinetic assay to measure Sos-catalyzed nucleotide exchange on K-Ras that is read on the Hamamatsu FDSS, and a kinase phosphorylation assay that is an adaptation of the LANCE technology. The Cell Biology group uses data from these assays in multiple cell lines to develop testable hypotheses regarding predictors of resistance and response to the targeted agents tested.


Olivia gained her pre-clinical drug discovery experience in the Oncology group at GlaxoSmithKline. She contributed to the due diligence decision regarding the in-licensing of the MEK inhibitor tramitinib (GSK2021212; currently in Phase III clinical trials), examining the effects of the inhibitor on downstream signaling. In her work on the B-Raf inhibitor program, she developed assays to directly measure phosphorylation of downstream substrates and to examine the broader consequences of target inhibition on signaling cascades. These assays were used to discover and develop inhibitors with potencies ranging from 0.1 – 10 nM against the target kinase. In addition, Oivia performed PD and efficacy studies of advanced compounds to demonstrate target and tumor growth inhibition in mouse xenograft models. She analyzed PK data from these studies to understand the relationship between dose, exposure, and response in this system. The candidate molecule from this program, debrafinib (GSK2118436), is currently in Phase III clinical trials. Olivia led and participated in efforts to discover inhibitors for additional kinases and other protein classes. For these programs, her teams and she developed cell-based assays to understand the specific molecular consequences of target inhibition, but also functional assays to understand how target inhibition contributes to the larger implications of oncogenesis. She was also focused on building and testing pre-clinical hypotheses to identify genetic markers of drug sensitivity and patient selection for specific targeted therapies.
 

Publications:

 
  1. Sun Q, JP Burke, J Phan, MC Burns, ET Olejniczak, AG Waterson, T Lee, OW Rossanese, and SW Fesik. Discovery of small molecules that bind to K-Ras and inhibit Sos-mediated activation. Angew Chem Int Ed. 51(25): 6140-6143 (2012).
  2. Souza-Fagundes EM, AO Frank, MD Feldkamp, DC Dorset, WJ Chazin, OW Rossanese, ET Olejniczak, and SW Fesik.  A high-throughput fluorescence polarization assay for the 70N domain of Replication Protein A. Anal Biochem. 2012 Feb15; 421(2): 742-9. PMC3274598
  3. Stellwagen, JC, GM Adjabeng, MR Arnone, SH Dickerson, C Han, KR Hornberger, AJ King, RA Mook, Jr., KG Petrov, TR Rheault, CM Rominger, OW Rossanese, KN Smitheman, AG Waterson, and DE Uehling.  Development of potent B-RafV600E inhibitors containing an arylsulfonamide headgroup. Bioorg Med Chem Lett. 2011 Aug1; 21(15): 4436-40.
  4. Losev, E, E Papanikou, OW Rossanese, and BS Glick.  Cdc1p is an endoplasmic reticulum-localized putative lipid phosphatase that affects Golgi inheritance and actin polarization by activating Ca2+ signaling. Mol Cell Biol. 2008 May; 28(10): 3336-43.  PMC2423168
  5. Patel, JC, OW Rossanese, and JE Galán.  The functional interface between Salmonella and its host cell: opportunities for therapeutic intervention. Trends Pharmacol Sci. 2005 Nov: 26(11): 564-570.
  6. Jiang, X*, OW Rossanese*, NF Brown, S Kujat-Choy, JE Galán, BB Finlay, and JH Brumell. The related effector proteins SopD and SopD2 from Salmonella enterica serovar Typhimurium contribute to virulence during systemic infection of mice. Mol Micro. 2004 Dec; 54(5): 1186-1198. *These authors contributed equally to this manuscript.
  7. Rossanese, OW and BS Glick. Deconstructing Golgi inheritance.  Traffic 2001Sep; 2(9): 589-596.
  8. Rossanese, OW, CA Reinke, BJ Bevis, AT Hammond, IB Sears, J O’Connor, and BS Glick.  A role for actin, Cdc1p and Myo2p in the inheritance of late Golgi elements in Saccharomyces cerevisiae. J Cell Biol. 2001 Apr2; 153(1): 47-61. PMC2185536
  9. Rossanese, OW, J Soderholm, BJ Bevis, IB Sears, J O’Connor, EK Williamson, and BS Glick.  Golgi structure correlates with transitional ER organization in Pichia pastoris and Saccharomyces cerevisiae. J Cell Biol. 1999 Apr 5; 145(1): 69-81. PMC2148216
  10. Séron, K, V Tieaho, C Prescianotto-Baschong, T Aust, M-O Blondel, P Guillaud, G Devilliers, OW Rossanese, BS Glick, H Riezman, S Keränen, and R Haguenauer-Tsapis. A yeast t-SNARE involved in endocytosis.  Mol Biol Cell. 1998 Oct; 9(10): 2873-89. PMC25562
  11. Sears, IB, J O’Connor, OW Rossanese, and BS Glick. A versatile set of integrating vectors for constitutive and regulated gene expression in Pichia pastoris.  Yeast. 1998 Jun 15; 14(8): 783-790.