Stephanie Pero, Ph.D.
Research Assistant Professor of Surgery
Research Program: Clinical Research
VCC Membership Level: Full Member
Contact Information
E-310 Given Building
89 Beaumont Avenue
University of Vermont
Burlington, VT, 05405
ph: (802) 656-0766
f: (802) 656-5833
Stephanie.Pero@uvm.edu
Biography
After spending 4 years as a post-doctoral associate at the Vermont Cancer Center, Dr. Pero became a Research Assistant Professor, Surgery in November 2006. Pero received her undergraduate and Master of Biology degrees from Worcester Polytechnic Institute and her Ph.D. at the University of Vermont. She has been awarded with several honors throughout her graduate education including the 26th UVM College of Medicine Graduate and Medical Student Presentation Award in 2001.
Research
The goals of Dr. Pero's research have been to develop phage-displayed random peptide libraries (RPLs) and to generate short peptide ligands to ErbB2 and associated molecules. She and her colleagues have successfully met these goals and have obtained short peptide ligands to ErbB2 and the downstream signal transduction molecule, Grb7. Although ErbB2 is not a tumor specific antigen, it is an attractive target since it is overexpressed on cancer cells of a number of different histologic types. It is also an important target because it is associated with the malignant phenotype. Blocking the function of ErbB2 leads to inhibition of proliferation of cancer cells as demonstrated in preclinical and clinical studies.
Several recent studies investigating ErbB2 expression have shown Grb7 as a prominent co-expressor. Therefore, our Aims are focused on developing ErbB2- and Grb7-binding ligands. She and her colleagues have shown the ErbB2-binding ligand, known as EC-1, to inhibit the phosphorylation of ErbB2 and inhibit the proliferation of overexpressing breast cancer cells. The Grb7-binding ligand, known as G718NATE, inhibits Grb7’s ability to bind to the family of ErbB receptor tyrosine kinases and specifically ErbB3. Importantly, they have shown that the cell permeable G7-18NATE-P peptide is able to successfully translocate across the cell membrane and significantly inhibit attenuated cell migration and peritoneal metastasis in a pancreatic cancer mouse model.
Pero is now working on characterizing, optimizing and maturing the ErbB2 and Grb7 peptides. She will use the lead peptide sequences as templates for generating modified molecules that will selectively inhibit ErbB2 and Grb7 functions, such as proliferation, migration and invasion of cells. Her long term goal is to develop targeted therapeutics to treat patients that overexpress ErbB2 and Grb7, which is found in a subset of breast, gastric and esophageal cancers.
Recent Publications
Porter CJ, Matthews JM, Mackay JP, Pursglove SE, Schmidberger JW, Leedman PJ, Pero SC, Krag DN, Wilce MCJ, Wilce JA. 2007. Grb7 SH2 domain structure and interactions with a cyclic petide inhibitor of cancer cell migration and proliferation. BMC Structure Biology. Sep 25;7;58
Li P, Jiang S, Pero SC, Oligino L, Krag DN, Michejda CJ, Roller PP. Design and synthesis of paclitaxel conjugated with an ErbB2-recognizing peptide, EC-1. 2007. Biopolymers. Nov;87(4):225-30.
Pero SC, Shukla GS, Cookson MM, Flemer S Jr, Krag DN. 2007. Combination treatment with Grb7 peptide and Doxorubicin or Trastuzumab (Herceptin) results in cooperative cell growth inhibition in breast cancer cells. Br J Cancer. May 21;96(10):1520-5.
Krag DN, Shukla GS, Shen GP, Pero S, Ashikaga T, Fuller S, Weaver DL, Burdette-Radoux S, Thomas C. 2006. Selection of tmor-binding ligands in cancer patients with phage display libraries. Cancer Res. Aug 1;66(15):7724-33.
Tanaka S, Pero SC, Taguchi K, Shimada M, Mori M, Krag DN, Arii S. 2006. A specific peptide ligand for Grb7 signal transduction protein inhibits invasion and metastasis of pancreatic cancer. Journal National Cancer Institute. 98(7) 491-498.
Pero SC, Shukla GS, Armstrong AL, Peterson D, Fuller SP, Godin K, Kingsley-Richards SL, Weaver DL, Bond J, Krag DN. 2004. Identification of a small peptide that inhibits the phosphorylation of ErbB2 and proliferation of ErbB2 overexpressing breast cancer cells. Int. J of Cancer. 111(6):951-960.
Pero SC, Daly RJ, Krag DN. 2003. Grb7-based molecular therapeutics in cancer. Expert reviews in Mol Medicine. 5:1-11. (Invited Review Article)
Other Key Publications
Krag DN, Fuller SP, Oligino L, Pero SC, Weaver DL, Soden AL, Mills S, Liu C, Peterson D. 2002. Phage-displayed random peptide libraries in mice: Toxicity after serial panning. Cancer Chemotherapy and Pharmacology. 50(4): 325-332.
Pero SC, Oligino L, Daly RJ, Soden AL, Liu C, Roller PP, Li P, Krag DN. 2002. Identification of novel non-phosphorylated ligands, which bind selectively to the SH2 domain of Grb7. Journal of Biological Chemistry. 277:11918-11926.
Adams DS, Nathans R, Pero SC, Sen A, Wakshull E. 2000. Activation of a Rel /CEBP-??¢-related transcription factor heteromer by PGG-Glucan in a murine monocytic cell line. Journal of Cellular Biochemistry. 77: 221-223.
Adams DS, Li Q, Tan X, Pero SC, Czop JK. 1998. Cloning and characterization of a family of cDNAs from human histiocyte macrophage cells encoding an arginine-rich basic protein related to the 70kD U1-snRNP splicing factor. Journal of Sequencing and Mapping. 94(4): 205-215.
Adams DS, Pero SC, Petro JB, Nathans R, Mackin WM, Wakshull E. 1997. PGG-Glucan activates NF-kB-like and NF-IL-6-like transcription factor complexed in a murine monocytic cell line. Journal of Leukocyte Biology. 62:865-873.
