Research Interests

Our laboratory is focused on discovering novel therapies for advanced-stage cancers. We have made significant advances in our understanding of tumor vasculature in ovarian cancer and how this may be an important therapeutic target. Tumors must recruit their own blood supply through a process of angiogenesis in order to meet their metabolic needs. However, the angiogenic program initiated by tumors is extremely aggressive and as a result, blood vessels are formed very quickly. Tumor vasculature is characterized by poorly-formed, dysfunctional vessels, with limited tissue perfusion. The result is a tumor with poor blood supply, areas of low oxygen, and high levels of pressure, due to leakage from the tumor vessels. This phenotype dramatically impedes the ability of therapeutic compounds to enter the tumor. Through our extensive collaborations, we have developed a therapeutic approach using the Type I Repeat region (3TSR) of Thrombospondin-1 (TSP-1). We have shown that 3TSR is toxic to tumor cells and specifically targets the dysfunctional, immature tumor vasculature. 3TSR prunes the tumor vessels back to its original, healthy parental vasculature. The result of 3TSR treatment is a smaller tumor with reduced pressure and normalized tissue perfusion. By re-establishing vascular supply to the tumor, we have been able to dramatically increase the uptake and efficacy of a number of therapies including chemotherapy drugs, oncolytic viruses, and immune therapies.

Our laboratory is also interested in identify the impact of the mevalonate pathway on metastatic disease. We have shown that upregulation of the mevalonate pathway is important in facilitating migration and survival of metastatic ovarian cancer cells. Inhibition of this pathway significantly impairs the ability of the metastatic cancer cells migrate within the abdomen and to initiate tumorigenic mechanisms.

Current Graduate Students

Bianca
Garlisi

PhD

Ann
Ram

PhD

Sylvia
Lauks

MSc

Selected Publications

• Matuszewska K, Santry LA, van Vloten JP, Au Yeung AWK, Major PP, Lawler J, Wootton SK, Bridle BW, Petrik J. Combining vascular normalization with an oncolytic virus enhances immunotherapy in a preclinical model of advanced stage ovarian cancer. Clin Canc Res.  25: 1624-1638; 2019
• Santry LA, van Vloten JP, Knapp JP, Matuszewska K, McAusland TM, Minott JA, Mould RC, Stegelmeier AA, Major PP, Wootton SK, Petrik J, Bridle BW. Tumor vasculature: friend or foe of oncolytic viruses? Cytokine Growth Factor Rev. S1359-6101, 2020
• Stegelmeier AA, Chan L, Mehrani Y, Petrik J, Wootton SK, Bridle B, Karimi K. Characterization of the impact of oncolytic vesicular stomatitis virus on the trafficking, phenotype, and antigen presentation potential of neutrophils and their ability to acquire a non-structural viral protein. Int J Mol Sci 21: 2020.
• Yu DL, Stegelmeier AA, Chow N, Rghei AD, Matuszewska K, Lawler J, Bridle BW, Petrik J, Wootton SK. AAV-mediated expression of 3TSR inhibits tumor and metastatic lesion development and extends survival in a murine model of epithelial ovarian carcinoma. Cancer Gene Ther. 27: 356-367, 2020
• Pal P, Hales K, Petrik J, Hales DB. Pro-apoptotic and anti-angiogenic actions of 2-methoxyestradiol and dcosahexaenoic acid, the biologically derived active compounds from flaxseed diet, in preventing ovarian cancer. J Ovarian Res. 25: 2019
• Van Vloten JP, Santry LA, McAusland TM, Karimi K, McFadden G, Petrik J, Wootton SK, Bridle BW. Quantifying antigen-specific T cell responses when using antigen-agnostic immunotherapies. Mol Ther Methods Clin Dev. 13: 154-166, 2019
• Kellenberger LK, Petrik J. Hyperglycemia promotes insulin-independent ovarian tumor growth.  Gynecologic Oncology. Epub ahead of print. 2018
• Subramaniam N, Petrik JJ, Vickaryous MK. VEGF, FGF-2 and TGFb expression in the normal and regenerating epidermis of geckos: implications for epidermal homeostasis and wound healing.  J. Anatomy. Epub ahead of print. Doi:10.1111/joa/12784. 2018
• Santry LA, McAusland TM, Wood GA, Petrik J, Susta L, Bridle BW, Wootton SK. Production and purification of high titre Newcastle disease virus for use in preclinical mouse models of cancer. Mol Ther Methods Clin Dev. 16: 181-191, 2017. 
• Dynes J, Osz K, Hooper A, Petrik J. Low dose metronomic delivery of cyclophosphamide is less detrimental to granulosa cell viability and ovarian function than maximum tolerated dose delivery in the mouse.  Biology of Reproduction. 97: 449-465, 2017
• Mould RC, AuYeung AWK, van Vloten JP, Susta L, Mutsaers AJ, Petrik J, Wood GA, Wootton SK, Karimi K, Bridle BW. Enhancing immune responses to cancer vaccines using mulit-site injections. Sci Rep. 7:1, 8322. 2017.
• Greenaway J, Virtanen C, Osz K, Revay T, Hardy D, Shepherd T, DiMattia G, Petrik J. Ovarian tumor growth is characterized by mevalonate pathway gene signature in an orthotopic, syngeneic mouse model of epithelial ovarian cancer. Oncotarget. 7: 47343-47365, 2016
• Linnerth-Petrik NM, Santry LA, Moorehead R, Jucker M, Wootton SK, Petrik J. Akt isoform specific effects in ovarian cancer progression. Oncotarget. 7: 74820-74833, 2016.
• Russell S, Duquette M, Liu J, Drapkin R, Lawler J, Petrik J. Combined therapy with thrombospondin-1 type I repeats (3TSR) and chemotherapy induces regression and significantly improves survival in a preclinical model of advanced stage epithelial ovarian cancer. FASEB J. 29: 576-588, 2015.
• Linnerth-Petrik NM, Santry LA, Petrik JJ, Wootton SK. Opposing functions of akt isoforms in lung tumor initiation and progression. PLoS One. 9(4):e94595,Apr 2014.
• Ten Kortenaar S, Lawler J, Petrik J. Anti-Angiogenic Therapy in Induction of Blood Vessel Normalization in the Treatment of Ovarian Cancer. Current Angiogenesis, 3: 203-214, 2014.
• Osz K, Ross M, Petrik J. The thrombospondin-1 receptor CD36 is an important mediator of ovarian angiogenesis and folliculogenesis. Reprd Biol Endocrinol. doi: 10.1186/1477-7827-12-21.March 2014.
• Greenaway JB, Koehler A, McCulloch CA, Petrik J, Brown TJ, Ringuette MJ. The impact of the ovarian microenvironment on the anti-tumor effect of SPARC on ovarian cancer. Biochem Cell Biol. 90: 96-107, 2012.
• Campbell NE, Greenaway J, Henkin J, Petrik J. ABT-898 induces tumor regression and prolongs survival in a mouse model of epithelial ovarian cancer.  Mol Cancer Ther. 10: 1876-1885 2011.
• McGray AJ, Gingerich T, Petrik JJ, LaMarre J. Rapid insulin-like growth factor-I-induced changes in granulosa cell thrombospondin-1 expression in vitro. J Reprod Dev. 57: 76-83, 2011.
• McGray AJ, Gingerich T, Petrik JJ, LaMarre J. Regulation of thrombospondin-1 expression through AU-rich elements in the 3’UTR of the mRNA. Cell Mol Biol Lett. 16: 55-68, 2010.
• Cambpell CI, Petrik JJ, Morehead RA. ErbB2 enhances mammary tumorigeneiss, oncogene-independent recurrence and metastasis in a model of IGF-IR-mediated mammary tumourigenesis. Mol Canc. 8: 235, 2010.
• McGray AJR, Gingerich T, Petrik JJ, LaMarre J. Rapid IGF-I induce changes in granulosa cell TSP-1 expression in vitro. J Reprod Dev. 57: 76-83, 2010.
• Jones RA, Petrik JJ, Moorehead RA. Preneoplastic changes persist after IGF-IR downregulation and tumor regression. Oncogene. 29: 4779-4786, 2010.
• Siwicky MD, Petrik JJ, Moorehead RA. The function of IGF-IR in NNK-mediated lung tumourigenesis. Lung 71: 11-18, 2010.
• Campbell NE, Kellenberger LD, Greenaway J, Linnerth-Petrik N, Moorehead RA, Petrik J. Extracellular matrix proteins and tumor angiogenesis. J Oncol. Epub ahead of print. 586905, June, 2010.
• Campbell NE, Greenaway J, Henkin J, Moorehead RA, Petrik J. The thrombospondin-1 mimetic ABT-510 increases the uptake and effectiveness of cisplatin and paclitaxel in a mouse model of epithelial ovarian cancer. Neoplasia. 12: 275-283, 2010.
• Kellenberger LD, Bruin JE, Greenaway J, Campbell N, Moorehead RA, Holloway AC, Petrik J. The role of dysregulated glucose metabolism in epithelial ovarian cancer. J Oncol. Epub ahead of print. 514310, Jan 2010.
• Linnerth NM, Siwicky MD, Campbell CI, Watson KL, Petrik JJ, Whitsett JA, Moorehead RA. Type I insulin-like growth factor receptor induces pulmonary tumourigenesis. Neoplasia. 11: 672-682, 2009.
• PetrikJ, Gerstein HC, Cesta CE, Kellenberger LD, Alfaidy N, Holloway AC. Effects of rosiglitazone on ovarian function and fertility in animals with reduced fertility following fetal and neonatal exposure to nicotine. Endocrine. 36: 281-290, 2009.
• Jones RA, Campbell CI, Wood GA, Petrik JJ, Moorehead RA. Reversibility and recurrence of IGF-IR-induced mammary tumors. Oncogene. 28: 2152-2162, 2009.
• Linnerth NM, Greenaway JB, Petrik JJ, Moorehead RA. cAMP response element-binding protein is expressed at high levels in human ovarian adenocarcinoma and regulates ovarian tumor cell proliferation.  Int J Gynecol Cancer. 2008 Nov-Dec;18(6):1248-57.
• Greenaway J, Henkin J Moorehead R, Lawler J, Petrik J. ABT-510 induces tumour cell apoptosis and inhibits ovarian tumour growth in an orthotopic, syngeneic model of epithelial ovarian cancer.  Mol Cancer Ther.  8: 64-74, 2009.