Bench to Bedside Institute for Translational Health Research and Innovation
Bench to Bedside Institute for Translational Health Research and Innovation

Dr. Jim Petrik

Meet Dr. Jim Petrik

MSc, PhD

Keywords: Ovarian Cancer, Anti-Angiogenic Therapies, Vascular Normalization, Tumour Vascular Perfusion, Angiogenesis, Mevalonate Pathway in Metastatic Disease, Tissue and Vascular Remodelling, Regenerative Medicine, Therapeutics for Ovarian Cancer and Metastatic Disease, Female Reproductive Biology

Profile(s): University of Guelph Experts, Comparative and Translational Regenerative Medicine Network, Department of Biomedical Science

Current Positions

  • Professor – Department of Biomedical Sciences, University of Guelph, Ontario Veterinary College
  • Part-Time Adjunct Professor – Department of Obstetrics and Gynecology, McMaster University, Health Sciences
  • Part-Time Adjunct Professor – Department of Experimental Oncology, Western University

Education and Employment Background

  • MSc, PhD – Molecular Biology (Western University, London, Ontario, Canada) 
  • Post Doctoral Fellowship (University of Guelph, Guelph, Ontario, Canada)

Research Themes & Interests

Our laboratory is invested in developing novel therapies for the treatment of advanced stage cancers. We are interested in remodelling tumor vasculature to improve the uptake and efficacy of a variety of anti-cancer therapies.  

As tumors grow, they need to recruit a new blood supply to support tissue growth and metabolism.  However, tumors typically initiate an excessively aggressive pro-angiogenic stimulus, resulting in inappropriate development of blood vessels within the tumor.  As a result, tumor vasculature is often dysfunctional, with numerous morphological and functional deformities.   The tumors then suffer from reduced vascular supply and hypoxia. An important consequence of this reduced vascular supply is reduced ability in uptake of therapeutic compounds into the tumor.  Impaired vascular supply, combined with the high interstitial fluid pressure within the tumor dramatically reduces the ability of chemotherapy drugs and other therapeutic compound to get into the tumor.  In a long-standing collaboration with Dr. Jack Lawler from Harvard University, we have developed a novel approach to specifically target this dysfunctional tumor vasculature, inducing pruning and regression of tumor vasculature back to healthy parental vessels.  The molecule we have worked with is thrombospondin-1 (TSP-1) is a naturally-occurring endogenous protein that signals through a cell-surface receptor (CD36) to specifically target tumor vessels.  We have developed therapeutic peptides from the type I repeat region  (3TSR) of TSP-1 that potently induces vascular normalization and reduces the level if interstitial fluid pressure in advanced stage ovarian tumors.  With this vascular normalization, we have been able to facilitate a dramatic increase in the uptake and efficacy of therapies such as chemotherapy drugs, oncolytic viruses, and immunotherapies.  This approach represents a novel and exciting approach to treating advanced stage ovarian cancer, a disease for which new therapies are desperately needed. 

Recent Research Focuses & Partnerships

  • Treatment of advanced stage ovarian cancer in animal models by targeting abnormal vascularization in tumours with anti-angiogenic peptides in collaboration with researchers at Harvard University. 
  • Targeting of the mevalonate pathway which 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.  
  • Determining the mechanisms by which cancer cells alter their metabolism and use of energy substrates.
  • Identify the roles that various factors play in regulating ovarian angiogenesis and female reproductive function.

Select Publications

  • 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.
  • 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
  • Wallace JG, Bellissimo CJ, Yeo E, Fei Xia Y, Petrik JJ, Surett MG, Bowdish DME, Sloboda DM. Obesity during pregnancy results in maternal intestinal inflammation, placental hypoxia, and alters fetal glucose metabolism at mid-gestation. Sci Rep. 9: 2019
  • 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
  • Gohir W, Kennedy KM, Wallace JG, Saoi M, Bellissimo CHJ, Britz-McKibbin P, Petrik J, Surette MG, Sloboda DM. High-fat diet modulates maternal intestinal adaptations to pregnancy, induces placental hypoxia, alters fetal gut barrier proteins, and immune markers. Journal of Physiology.  Accepted for Publication, Apr 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
  • Astill J, Alkie T, Yitbarek A, Taha-Abdelaziz K, Shojadoost B, Petrik JJ, Nagy E, Sharif S. A comparison of toll-like receptor 5 and 21 ligands as adjuvants for a formaldehyde inactivated H9N2 avian influenza virus vaccine in chickens. Viral Immunol. 31: 605-612, 2018
  • Astill J, Alkie T, Yitbarek A, Taha-Abdelaziz K, Bavananthasivam J, Nagy E, Petrik J, Sharif S.  Induction of Immune response in chickens primed in ovo with an inactivated H9N2 avian influenza virus vaccine. BMC Res Notes. 11: 428, 2019
  • Astill J., Alkie T, Yitbarek A, Abdelaziz KTA, Bavananthasivam J, Nagy E, Petrik JJ, Sharif S. Examination of the effects of virus inactivation methods on the induction of antibody- and cell-mediated immune responses against whole inactivated H9N2 avian influenza virus vaccines in chickens. Vaccine. 36: 3908-3916, 2018.
  • 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
  • Chan KA, Jazwiec PA, GOhir W, Petrik JJ, Sloboda DM. Maternal nutrient restriction impairs young adult offspring ovarian signaling resulting in reproductive dysfunction and follicle loss. Biol Reprod. 98: 664-682, 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.
  • Tsoulis MW, Chang PE, Moore CJ, Chan KA, Ghoir W, Petrik J, Vickers MH, Connor KL, Sloboda DM. Maternal high-fat diet-induced loss of fetal oocytes is associated with compromised follicle growth adult rat offspring. Biol Reprod. 94: 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.
  • Moore CJ, DeLong NE, Chan KA, Holloway AC, Petrik J, Sloboda DM. Perinatal administration of a selective serotonin reuptake inhibitor induces impariments in reproductive function and follicular dynamics in female rat offspring. Reprod Sci. 22: 1397-1311, 2015.
  • Chan K, Bernal AB, Vickers MH, Gohir W, Petrik J. Sloboda DM. Early life exposure to undernutrition induces ER stress, apoptosis, and reduced vascularization in ovaries of adult rat offspring. Biol Reprod. 92: 2015.
  • De Long NE, Gugesell MK, Petrik J, Holloway AC. Fetal exposure to sertraline hydrochloride impairs pancreatic β-cell development. Endocrinology. 156: 1952-1957, 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.
  • Hayes EK, Tessier DR, Percival ME, Holloway AC, Petrik JJ, Gruslin A, Raha S. Trophoblast invasion and blood vessel remodeling is altered in a rat model of lifelong maternal obesity. Reprod Sci. 21: 648-657, 2013.
  • Hayes EK, Lechowicz A, Petrik JJ, Storozhuk Y, Paez-Parent S, Dai Q, Samjoo IA, Mansell M, Gruslin A, Holloway AC, Raha S. Adverse fetal and neonatal outcomes associated with a life-long high fat diet: role of altered development of the placental vasculature. PLoS One.  7: e33370, 2012.
  • Jeon BG, Rho GJ, Betts DH, Petrik JJ, Favetta LA, King WA. Low levels of X-inactive specific transcript in somatic cell nuclear transfer embryos drived from female bovine freemartin donor cells. Sex Dev. 6: 151-159, 2012.
  • Pistilli MJ, Petrik JJ, Holloway AC, Crankshaw DJ. Immunohistochemical and functional studies on calcium-sensing receptors in rat uterine smooth muscle. Clin Exp Pharmacol Physiol. 39: 37-42, 2012.
  • 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.
  • Petre MA, Petrik J, Ellis R, Inman MD, Holloway AC, Labiris NR. Fetal and neonatal exposure to nicotine disrupts postnatal lung development in rats: role of VEGF and its receptors. Int J Toxicol. 30: 244-252, 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.
  • Bruin JE, Petrik JJ, Hyslop JR, Raha S, Tarnopolsky MA, Gerstein HC, Holloway AC. Rosiglitazone improves pancreatic mitochondrial function in an animal model of dysglycemia:  role of the insulin-like growth factor axis. Endocrine. 37: 303-311, 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.
  • Full link to publications: https://www.researchgate.net/profile/Jim-Petrik-2

Highlights

Contact

Email: jpetrik@uoguelph.ca 
Phone: (519) 824-4120 Ext: 54921
Office: OVC 3627 

Ontario Veterinary College
University of Guelph
50 Stone Road E.,
Guelph, ON, Canada, N1G 2W1