As part of the Ovarian Epithelial Cancer Pathobiology program in the Department of Pathology at USF, the research focus in my lab is on early molecular changes responsible for ovarian epithelial transformation. In particular, we are interested in the molecular regulation of telomerase, DNA repair and apoptosis associated with a familial risk for ovarian cancer.
Our research concerns the signal transduction pathways involved in early stages of ovarian oncogenesis. We are examining the molecular mechanism(s) that regulate telomerase, a ribonucleoprotein expressed in over 90% of all cancers. Studies in this laboratory also indicate that telomerase re-expression appears to confer increased cancer cell survival and resistance to chemotherapeutic-mediated apoptosis associated with elevated levels of anti-apopototic proteins including survivin and Bcl-2. Consequently, a recent translational study revealed Bcl-2 present at levels 10x greater in urine samples from women with ovarian cancer compared to normal controls or women with benign gynecologic disease.
Lastly, in agreement with clinical reports that certain women with hereditary ovarian cancer initially respond better to chemotherapy, other studies in this laboratory are directed at understanding the molecular mechanism(s) by which BRCA1 amino-terminal mutations result in enhanced cellular apoptosis following genotoxic stress.
Thus, while elevated urinary levels of Bcl-2 may provide a novel, safe, sensitive and economic method ovarian cancer detection, inhibition of the signaling pathways regulating telomerase activity or activation of cellular BRCA1 amino-terminal mutation targets may be beneficial for the treatment of ovarian cancer, an insipid disease with the highest mortality of all gynecological cancers.
Awards/Honors
Robert J. Grasso Award (University of South Florida - 2012)
Excellence in Innovation Award (National Academy of Inventors - 2010)
University of South Florida Women in Leadership and Philanthropy Faculty Research Award (University of South Florida - 2008)
Robert J. Grasso Award (University of South Florida - 1999)
Upjohn Travel Award (Upjohn Company - 1993)
Outstanding Dissertation Award (American Association of Anatomists - 1992)
Student Travel Award (University of British Columbia - 1990)
Student Travel Award (American Society of Cell Biology - 1990)
Student Travel Award (American Association of Anatomists - 1990)
University of British Columbia Graduate Fellowship (University of British Columbia - 1987)
Evelyn Martin Memorial Fellowship (British Columbia Fouhdation for Non-Animal Research - 1987)
University of British Columbia MacMillan Family Fellowship (University of British Columbia - 1985)
Memberships
Member (National Academy of Inventors, 2012 - Present)
Member (Women in Cancer Research, American Association for Cancer Research, 2005 - Present)
Member (Minorities in Cancer Research, American Association for Cancer Research, 2005 - Present)
Member (American Association for Cancer Research, 1991 - Present)
Member (Women in Academic medicine, USF Health, 2007 - 2009)
Member (American Society for Investigative Pathology, 2005 - 2007)
Recent Publications
Woolery KT, Mohamed M, Linger RJ, Dobrinski KP, Roman J, Kruk PA. BRCA1 185delAG Mutation Enhances Interleukin-1β Expression in Ovarian Surface Epithelial Cells.BioMed research international. 2015: 652017, 2015.
Dobrinksi K, Esposito NN, Kruk, PA, Wenham R, Hoffman M, Coppola D, Bai W, Zhang X, Siddique N, Nicosia SV. Procurement and cytological feature of human fallopian tube fimbrial cells by ex vivo imprinting and washing.J. Am. Soc. Cytopathol. 3: 309-318, 2014.
Onen, Onursal|Sisman, Alper|Gallant, Nathan D.|Kruk, Patricia|Guldiken, Rasim A Urinary Bcl-2 Surface Acoustic Wave Biosensor for Early Ovarian Cancer DetectionSensors. 12(6) : 7423-7437, 2012.
Xu C-X, Tan L, Yang H, Permuth-Wey J, Kruk PA, Wenham RM, Nicosia SV, Lancaster JM, Sellers TA, Cheng JQ. Mir-214 regulates ovarian cancer cell stemness by targeting
p53/NanogJournal of Biological Chemistry. : 34970-34978, 2012.
Shen Z, Ravi K, Jinwal U, Nicosia SV, Kruk P, Xiaohang Z, Bai W. 1,25-dihydroxyvitamin
D3 suppresses telomerase expression and human cancer cell survival through miR-498Journal of Biological Chemistry. 287: 41297-309, 2012.
Woolery KT, Kruk PA. Ovarian Epithelial-Stromal Interactions: Role of Interleukins 1 and 6.Gynecol. Intl. : 358493, 2011, 2011.
Drenberg CD, Saunders BO, Wilbanks GD, Chen R, Nicosia RF, Kruk PA, Nicosia SV. Urinary angiostatin levels are elevated in patients with epithelial ovarian cancer.Gynecologic oncology. 117(1) : 117-24, 2010.
Linger RJ, Kruk PA. BRCA1 16 years later: risk-associated BRCA1 mutations and their functional implications.The FEBS journal. 277(15) : 3086-96, 2010.
Anderson NC, Bermudez Y, Badgwell D, Chen R, Nicosia SV, Bast RC, Kruk PA*. Urinary levels of Bcl-2 are elevated in ovarian cancer patientsGynecol Oncol. 112(1) : 60-67, 2009.
Guo J, Shu S-K, He L, Lee Y-C, Kruk PA, Grenman S, Nicosia SV, Coppola D, Cheng JQ. Deregulation of the IKBK oncogene is associated with tumor progression, poor prognosis and cisplatin resistance in ovarian cancer.Amer. J. Pathol.. 175(1) : 324-333, 2009.
Walker RF, Pakula LC, Sutcliffe MJ, Kruk PA, Graakjaer J, Shay JW. A case study of disorganized development and its possible relevance to genetic determinants of aging.Mech. Ageing Develop.. 130(5) : 350-356, 2009.
Zhang, Y|Zhang, M|Dong, H|Yong, S|Li, X|Olashaw, N|Kruk, P A|Cheng, J Q|Bai, W|Chen, J|Nicosia, S V|Zhang, X Deacetylation of cortactin by SIRT1 promotes cell migrationOncogene. 28(3) : 445-460, 2009.
Drenberg C, Livingston S, Chen R, Kruk PA, Nicosia SV. Expression of Semaphorin 3F and its receptors in epithelial ovarian cancer, fallopian tubes, and secondary Mullerian tissues.Obstet. Gynecol. Intl.. 1: 1-8, 2009.
Anderson NS, Turner L, Livingston S, Chen R, Nicosia SV, Kruk PA*. Bcl-2 expression is altered with ovarian tumor progression: an immunohistochemical evaluation.J. Ovarian Research.. 2(16) : 1-11, 2009.
Yang H, Kong W, he L, Zhao J-J, O''Donnell JD, Wang J, Wenham RM, Copppola D, Kruk PA, Nicosia SV, Cheng JQ. MicroRNA expression profiling in human ovarian cacner: miRNA-214 induces cell survival and cisplatin resistance by targeting PTENCancer Research. 68: 424-433, 2008.
O''Donnell JD, Johnson NC, Turbeville TD, Alfonso MY, Kruk PA. BRCA1 185delAG truncation protein, BRAt, amplifies caspase-medatied apoptosis in ovarian cancer cellsIn Vitro Cell Dev. Biol.. 44: 357-367, 2008.
Bermudez Y, Yang H, Cheng JQ, Kruk PA. Pyk2/ERK1/2 mediate Sp1- and cMyc-dependent induction of telomerase activity by epidermal growth factorGrowth Factors. 26: 1-11, 2008.
Bermudez Y, Yang H, Saunders BO, Cheng JQ, Nicosia SV, Kruk PA. VEGF- and LPA-induced telomerase in human ovarian cancer cells is Sp1-dependent.Gynecologic Oncology. 106: 526-537, 2007.
Bermudez, Yira|Erasso, Diana|Johnson, Nicole C|Alfonso, Michelle Y|Lowell, Nancy E|Kruk, Patricia A Telomerase confers resistance to caspase-mediated apoptosisClinical Interventions in Aging. 1(2) : 155-167, 2006.
Yang H, He L, Kruk P, Nicosia SV, Cheng JQ. Aurora-A induces cell survival and chemoresistance by activation of Akt through a p53-dependent manner in ovarian cancer cells.International journal of cancer. Journal international du cancer. 119(10) : 2304-2312, 2006.
Tebes SJ, Kruk PA. The genesis of RNA interference, its potential clinical applications, and implications in gynecologic cancer.Gynecologic oncology. 99(3) : 736-741, 2005.
Alfonso-De Matte MY, Kruk PA. Phosphatidylinositol triphosphate kinase-dependent and c-jun NH2-terminal kinase-dependent induction of telomerase by calcium requires Pyk2.Cancer research. 64(1) : 23-26, 2004.
Yang H, Ou CC, Feldman RI, Nicosia SV, Kruk PA, Cheng JQ. Aurora-A kinase regulates telomerase activity through c-Myc in human ovarian and breast epithelial cells.Cancer research. 64(2) : 463-467, 2004.
Johnson NC, Dan HC, Cheng JQ, Kruk PA. BRCA1 185delAG mutation inhibits Akt-dependent, IAP-mediated caspase 3 inactivation in human ovarian surface epithelial cells.Experimental cell research. 298(1) : 9-16, 2004.
Nicosia SV, Wilbanks GD, Saunders B, Mayer J, Cardosi RJ, Kruk PA, Cheng J, Bai W, Coppola D, Fiorica J. Cytology of human ovarian surface epithelial brushings.Cancer. 102(1) : 1-10, 2004.
Shoup BL, Kruk PA. Inhibition of telomerase improves chemosensitivity in cisplatin resistant ovarian cancer cellsCancer Therapy. 2: 501-510, 2004.
Nicosia SV, Bai W, Cheng JQ, Coppola D, Kruk PA. Oncogenic pathways implicated in ovarian epithelial cancer.Hematology/oncology clinics of North America. 17(4) : 927-943, 2003.
Johnson NC, Kruk PA. BRCA1 Zinc RING Finger Domain Disruption Alters Caspase Response in Ovarian Surface Epithelial Cells.Cancer Cell International. 2(1) : 1-16, 2002.
Alfonso-De Matte MY, Yang H, Evans MS, Cheng JQ, Kruk PA. Telomerase is regulated by c-Jun NH2-terminal kinase in ovarian surface epithelial cells.Cancer research. 62(16) : 4575-45078, 2002.
Alfonso-De Matte MY, Moses-Soto H, Kruk PA. Calcium-mediated telomerase activity in ovarian epithelial cells.Archives of biochemistry and biophysics. 399(2) : 239-244, 2002.
Kruk PA, Godwin AK, Hamilton TC, Auersperg N. Telomeric instability and reduced proliferative potential in ovarian surface epithelial cells from women with a family history of ovarian cancer.Gynecologic oncology. 73(2) : 229-236, 1999.
Kruk PA, Bohr VA. Telomeric length in individuals and cell lines with altered p53 status.Radiation oncology investigations. 7(1) : 13-21, 1999.
Kruk PA, Orren DK, Bohr VA. Telomerase activity is elevated in early S phase in hamster cells.Biochemical and biophysical research communications. 233(3) : 717-722, 1997.
Kruk PA, Balajee AS, Rao KS, Bohr VA. Telomere reduction and telomerase inactivation during neuronal cell differentiation.Biochemical and biophysical research communications. 224(2) : 487-492, 1996.
Kruk PA, Rampino NJ, Bohr VA. DNA damage and repair in telomeres: relation to aging.Proceedings of the National Academy of Sciences of the United States of America. 92(1) : 258-262, 1995.
Kruk PA, Auersperg N. A line of rat ovarian surface epithelium provides a continuous source of complex extracellular matrix.In vitro cellular & developmental biology. Animal. 30A(4) : 217-225, 1994.
Auersperg N, Maines-Bandiera SL, Dyck HG, Kruk PA. Characterization of cultured human ovarian surface epithelial cells: phenotypic plasticity and premalignant changes.Laboratory investigation; a journal of technical methods and pathology. 71(4) : 510-518, 1994.
Kruk PA, Uitto VJ, Firth JD, Dedhar S, Auersperg N. Reciprocal interactions between human ovarian surface epithelial cells and adjacent extracellular matrix.Experimental cell research. 215(1) : 97-108, 1994.
Bohr VA, Kruk PA, Webb D, Ji J, Evans MK. DNA repair and genomic instability in cancer and agingBiomedical gerontology. 18: 20-24, 1994.
Kruk PA, Auersperg N. Human ovarian surface epithelial cells are capable of physically restructuring extracellular matrix.American journal of obstetrics and gynecology. 167(5) : 1437-1443, 1992.
Maines-Bandiera SL, Kruk PA, Auersperg N. Simian virus 40-transformed human ovarian surface epithelial cells escape normal growth controls but retain morphogenetic responses to extracellular matrix.American journal of obstetrics and gynecology. 167(3) : 729-735, 1992.
Auersperg N, Maclaren IA, Kruk PA. Ovarian surface epithelium: autonomous production of connective tissue-type extracellular matrix.Biology of reproduction. 44(4) : 717-724, 1991.
Kruk PA, Auersperg N. Percoll centrifugation eliminates mold contaminants from cell cultures.In vitro cellular & developmental biology : journal of the Tissue Culture Association. 27A(4) : 273-276, 1991.
Kruk PA, Maines-Bandiera SL, Auersperg N. A simplified method to culture human ovarian surface epithelium.Laboratory investigation. 63(1) : 132-136, 1990.
Reid PE, Owen DA, Kruk PA, Maitland ME. Histochemical classification based upon reaction types and its application to carbohydrate histochemistry.The Histochemical journal. 22(5) : 299-308, 1990.
Auersperg N, Kruk PA, MacLaren IA, Watt FM, Mydral SE. Heterogeneous expression of keratin, involucrin, and extracellular matrix among subpopulations of a poorly differentiated human cervical carcinoma: possible relationships to patterns of invasion.Cancer research. 49(11) : 3007-3014, 1989.
Enesco HE, Kruk PA. Dietary restriction reduces fluorescent age pigment accumulation in mice.Experimental gerontology. 16(4) : 357-361, 1981.
Kruk PA, Enesco HE. alpha-Tocopherol reduces fluorescent age pigment levels in heart and brain of young mice.Experientia. 37(12) : 1301-1302, 1981.
Bermudez Y, Ahmadi S, Lowell NE, Kruk PA. Vitamin E suppresses telomerase activity in ovarian cancer cells.Cancer detection and prevention. 31(2) : 119-128, 2007.
Positions Held
Associate Professor (Pathology & Cell Biology, University of South Florida 2003 - 2008)
Assistant Professor (Pathology, Univeristy of South Florida 1996 - 2003)
