Pheruza Tarapore

Pheruza Tarapore

Assistant Professor

Kettering Lab Complex

356

COM EH EGMT Tarapore Lab - 0056

University of Cincinnati
Department of Environmental Health
Cincinnati, Ohio 45267-0056

Professional Summary

     RNA therapies for Cancer
This project aims to both develop effective RNA therapies to target advanced prostate, breast and ovarian cancers and to develop more sensitive and specific bio-imaging agents. Our studies are aimed at engineering the delivery vehicle by coupling it with other therapeutic components (such as pro-apoptotic microRNA, siRNA and lncRNA) or drugs and MRI contrast agents.

     Identification of Abiraterone resistance markers
Another project involves use of patient derived xenograft models for the identification of Abiraterone resistance markers for prostate cancer. This is important for designing therapeutic interventions sensitizing prostate cancers to combination Abiraterone therapies, and for prognostic applications to monitor and predict for disease relapse.

     Environmental epigenetics and cancer
This project aims to investigate epigenetic regulation of gene expression in response to environmental endocrine disruptors. Epigenetic changes in DNA methylation, microRNA/non-coding RNA and histone modifications can reprogram gene expression and exert long-lasting as well as inheritable effects in humans. Effects of early life exposures to endocrine disruptors such as Bisphenol A as well as high fat and olive oil diets, will be studied in the Sprague Dawley rat. We will investigate how these diet can alter epigenetics, and dissect the underlying mechanisms for prostate cancer development, and male reproductive dysfunction.
 

Education

Ph.D., University of Cincinnati Cincinnati, 1997 (Molecular Genetics)

M.S., University of Bombay India, 1989 (Microbiology)

B.S., University of Bombay India, 1986 (Microbiology)

Positions and Work Experience

2011 - Assistant Professor, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH

2007 -2011 Research Scientist, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH

2001 -2007 Research Scientist, Department of Cell and Cancer Biology, University of Cincinnati College of Medicine, , Cincinnati, OH

Research and Practice Interests

~~My research focuses on two separate fields Cancer therapy and Health outcomes of Endocrine disruptors.

I am part of a pilot study examining the risk of prostate cancer and testicular reprogramming following dietary fatty acid consumption and BPA exposure during prenatal development, a critical susceptible window. Additionally, the short and long term effects of low doses of endocrine disruptors on the cell centrosome duplication cycle in prostate cells, and the underlying mechanism are being investigated. I have been collaborating with Dr. Shuk-mei Ho looking at the role of Bisphenol A in increasing the risk of pro-inflammatory (PIN) lesions in the prostate, and prostate cancer incidence. Decreasing the risk of cancer development and/or progression is also important. The possibility of environmental exposures such as bisphenol A having an effect on fertility and increasing risk to prostate cancer initiation cannot be easily discounted. Given that exposure to BPA is ubiquitous in the U.S., and that the Bisphenol A replacement Bisphenol S is also estrogenic, this study is of paramount interest for the general population and a legitimate public health concern. My long term goal is to develop novel molecular predictors of at-risk populations for endocrine disrupting chemicals (EDCs)-modulated effects on male reproductive tract disorders/diseases such as prostate cancer, and increase our understanding of the underlying mechanism(s).

Some of my studies also focus on developing tissue targeted diagnostic and therapeutic strategies for prostate, breast and ovarian cancer. I am interested on finding effective RNA therapies to target advanced cancers, and to develop more sensitive and specific bio-imaging agents. Our studies are aimed at developing an RNA aptamer based approach for treating cancers. This involves development of RNA vehicles to deliver pro-apoptotic microRNA and siRNA targeting pro-survival genes, to specific tissues. The RNA vehicles consist of the relatively non-immunogenic and stable RNA aptamers specific for prostate, breast or ovarian cancer cells. We are also developing various strategies to engineer the delivery vehicle and couple it with the therapeutic components to increase efficiency of delivery. Along the same line, we are  interesting in identifying novel biomarkers involved in abiraterone resistance, with the aim to either use them for therapy, or for prognostic applications to predict Abiraterone sensitivity/resistance.  

Centrosomes have recently gained importance because of their potential role in carcinogenesis. Centrosomes organize the mitotic spindle - the collection of protein filaments that pull the duplicated chromosomes (DNA) apart during cell division; thus ensuring that the two daughter cells each get one centrosome and a complete set of chromosomes. Abrogation of centrosome duplication control results in abnormal amplification of centrosomes, which in turn leads to aberrant mitosis and increases the frequency of chromosome transmission errors. We are determining how endocrine disruptors such as BPA and its analogues deregulate controls on centrosome duplication, leading to centrosome hyperamplification. For this, we are examining the function of lncRNA (long non-coding RNA) in this process.
 

Research Support

Investigators:Tarapore, Pheruza; Ho, SM; Leung, Yuet-Kin. BAD DATE -06-30-2018 Department of the Army Medical Research and Materiel Command MicroRNA Biomarkers to Generate Sensitivity to Abiraterone-Resistant Prostate Cancer Role:PI $375,000 Active Type:Grant

Investigators:Lee, Joo-Youp; Tarapore, Pheruza; Leung, Yuet-Kin. 2015 -2016 Cincinnati Cancer Center Pilot Program Novel Targeted and Controlled Gene and Drug Co-delivery System for Metastatic and Drug Resistant Breast Cancer Role:Co-PI 36,000 Active Type:Grant

Investigators:Lee, Joo-Youp; Tarapore, Pheruza; Leung, Yuet-Kin. 2015 -2016 Marlene Harris-Ride Cincinnati Breast Cancer Pilot Grant Program Targeted and Controlled Co-delivery of miRNA Inhibitor and Chemotherapeutic Drug for HER2 Positive Breast Cancer Role:Co-PI $40,000 Active Type:Grant

2014 -2015 University of Cincinnati Cancer Institute The UCCI Retreat Drake Pilot Grant for Innovative Idea 2014 Role:Co-I $100,000 Active Type:Grant

Investigators:Tarapore, Pheruza 2014 -2015 Center for Environmental Genetics, Pilot Projects Grant Program. To study reprograming of lncRNA in prostate cancer cells by bisphenol A and its analogues. $30,000 Completed Type:Grant

Grant: #VA IPA - Tarapore Investigators:Tarapore, Pheruza 04-01-2013 -03-31-2014 Department of Veterans Affairs Intergovernmental Personnel Act Agreement - Tarapore Role:PI $62,394.66 Completed

Investigators:Tarapore, Pheruza 03-2013 -02-2014 Center for Environmental Genetics. To study reprogramming of DNA methylome in the PND21 testis by high fat diet and bisphenol A. Role:PI 34,800 Completed Type:Grant

2013 -2014 Center for Environmental Genetics Pilot Project Program Mentee/Mentor Award: Reprograming of DNA methylome in the testis by high fat diet and bisphenol A Role:PI $25,000 Completed Type:Grant

Grant: #5R21EB012122-02 Investigators:Smithrud, D. 04-01-2012 -03-31-2016 NIH/NIBIB Smart, Enzyme-Activated MRI Contrast Agents For Cancer Detection. Role:Collaborator Active Type:Grant

Investigators:Tarapore, Pheruza; Smithrud, D.; Lee; Ho, SM. 2012 -12-2013 University of Cincinnati Medical Center Provost’s Pilot Research Program Award: Detecting Ovarian Cancers with Tissue-Specific MRI Contrast Agents Role:PI $40,000 Completed Type:Grant

Investigators:Tarapore, Pheruza 2012 -2014 Center for Environmental Genetics Next Generation Biomedical Investigator Role:PI 34,800 Completed Type:Grant

Grant: #W81XWH-10-1-0367 Investigators:Tarapore, Pheruza 05-15-2010 -05-14-2014 Department of the Army Medical Research and Materiel Command Targeted Delivery of Therapeutic RNA into Prostate Cancers Role:PI $353,250.00 Completed Type:Grant

Investigators:Tarapore, Pheruza 07-01-2002 -06-30-2003 American Cancer Society - Ohio Chapter Functional Interaction Between P53 and BRCA1in Regulation of Centrosome Duplicaiton in Breast Cancer Cells Role:PI $20,000.00 Closed Level:Private Non-Profit

Grant: #VA IPA - Tarapore Investigators:Tarapore, Pheruza 07-01-2017 -06-30-2018 Department of Veterans Affairs VA IPA Role:PI $13,358.00 Active Level:Federal

Publications

Peer Reviewed Publications

Tarapore, Pheruza; Ying, Jun; Ouyang, Bin; Burke, Barbara; Bracken, Bruce; Ho, Shuk-Mei (2014. )Exposure to bisphenol A correlates with early-onset prostate cancer and promotes centrosome amplification and anchorage-independent growth in vitro.PloS one, ,9 (3 ),e90332

Lee, Ming-Tsung; Ho, Shuk-Mei; Tarapore, Pheruza; Chung, Irving; Leung, Yuet-Kin (2013. )Estrogen receptor beta isoform 5 confers sensitivity of breast cancer cell lines to chemotherapeutic agent-induced apoptosis through interaction with Bcl2L12. Neoplasia (New York, N.Y.), ,15 (11 ),1262-71

Lee, Ming-Tsung; Leung, Yuet-Kin; Chung, Irving; Tarapore, Pheruza; Ho, Shuk-Mei (2013. )Estrogen receptor beta (ERbeta1) transactivation is differentially modulated by the transcriptional coregulator Tip60 in a cis-acting element-dependent manner.The Journal of biological chemistry, ,288 (35 ),25038-52

Smithrud, David B; Wang, Xiaoyang; Tarapore, Pheruza; Ho, Shuk-Mei (2013. )Crown Ether Host-Rotaxanes as Cytotoxic Agents.ACS medicinal chemistry letters, ,4 (1 ),27-31

Isaac, Jared; Tarapore, Pheruza; Zhang, Xiang; Lam, Ying-Wai; Ho, Shuk-Mei (2012. )Site-specific S-nitrosylation of integrin ?6 increases the extent of prostate cancer cell migration by enhancing integrin alpha1 association and weakening adherence to laminin-1.Biochemistry, ,51 (48 ),9689-97

Tarapore, Pheruza; Hanashiro, Kazuhiko; Fukasawa, Kenji (2012. )Analysis of centrosome localization of BRCA1 and its activity in suppressing centrosomal aster formation.Cell cycle (Georgetown, Tex.), ,11 (15 ),2931-46

Leung, Yuet-Kin; Lee, Ming-Tsung; Lam, Hung-Ming; Tarapore, Pheruza; Ho, Shuk-Mei (2012. )Estrogen receptor-beta and breast cancer: translating biology into clinical practice.Steroids, ,77 (7 ),727-37

Ho, Shuk-Mei; Johnson, Abby; Tarapore, Pheruza; Janakiram, Vinothini; Zhang, Xiang; Leung, Yuet-Kin (2012. )Environmental epigenetics and its implication on disease risk and health outcomes.ILAR journal / National Research Council, Institute of Laboratory Animal Resources, ,53 (3-4 ),289-305

Tarapore, Pheruza; Shu, Yi; Guo, Peixuan; Ho, Shuk-Mei (2011. )Application of phi29 motor pRNA for targeted therapeutic delivery of siRNA silencing metallothionein-IIA and survivin in ovarian cancers.Molecular therapy : the journal of the American Society of Gene Therapy, ,19 (2 ),386-94

Tarapore, Pheruza; Shinmura, Kazuya; Suzuki, Hitoshi; Tokuyama, Yukari; Kim, Song-Hee; Mayeda, Akila; Fukasawa, Kenji (2006. )Thr199 phosphorylation targets nucleophosmin to nuclear speckles and represses pre-mRNA processing.FEBS letters, ,580 (2 ),399-409

Shinmura, Kazuya; Tarapore, Pheruza; Tokuyama, Yukari; George, Kyle R; Fukasawa, Kenji (2005. )Characterization of centrosomal association of nucleophosmin/B23 linked to Crm1 activity.FEBS letters, ,579 (29 ),6621-34

Mayhew, Christopher N; Bosco, Emily E; Fox, Sejal R; Okaya, Tomohisa; Tarapore, Pheruza; Schwemberger, Sandy J; Babcock, George F; Lentsch, Alex B; Fukasawa, Kenji; Knudsen, Erik S (2005. )Liver-specific pRB loss results in ectopic cell cycle entry and aberrant ploidy.Cancer research, ,65 (11 ),4568-77

Tarapore, Pheruza; Fukasawa, Kenji (2002. )Loss of p53 and centrosome hyperamplification.Oncogene, ,21 (40 ),6234-40

Tarapore, Pheruza; Okuda, Masaru; Fukasawa, Kenji (2002. )A mammalian in vitro centriole duplication system: evidence for involvement of CDK2/cyclin E and nucleophosmin/B23 in centrosome duplication. Cell cycle (Georgetown, Tex.), ,1 (1 ),75-81

Shinmura, K; Bennett, R A; Tarapore, P; Fukasawa, K (2007. )Direct evidence for the role of centrosomally localized p53 in the regulation of centrosome duplication.Oncogene, ,26 (20 ),2939-44

Tarapore, P; Tokuyama, Y; Horn, H F; Fukasawa, K (2001. )Difference in the centrosome duplication regulatory activity among p53 'hot spot' mutants: potential role of Ser 315 phosphorylation-dependent centrosome binding of p53.Oncogene, ,20 (47 ),6851-63

Tokuyama, Y; Horn, H F; Kawamura, K; Tarapore, P; Fukasawa, K (2001. )Specific phosphorylation of nucleophosmin on Thr(199) by cyclin-dependent kinase 2-cyclin E and its role in centrosome duplication.The Journal of biological chemistry, ,276 (24 ),21529-37

Tarapore, P; Horn, H F; Tokuyama, Y; Fukasawa, K (2001. )Direct regulation of the centrosome duplication cycle by the p53-p21Waf1/Cip1 pathway.Oncogene, ,20 (25 ),3173-84

Okuda, M; Horn, H F; Tarapore, P; Tokuyama, Y; Smulian, A G; Chan, P K; Knudsen, E S; Hofmann, I A; Snyder, J D; Bove, K E; Fukasawa, K (2000. )Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome duplication. Cell, ,103 (1 ),127-40

Mussman, J G; Horn, H F; Carroll, P E; Okuda, M; Tarapore, P; Donehower, L A; Fukasawa, K (2000. )Synergistic induction of centrosome hyperamplification by loss of p53 and cyclin E overexpression.Oncogene, ,19 (13 ),1635-46

Tarapore, P; Fukasawa, K (2000. )p53 mutation and mitotic infidelity. Cancer investigation, ,18 (2 ),148-55

Carroll, P E; Okuda, M; Horn, H F; Biddinger, P; Stambrook, P J; Gleich, L L; Li, Y Q; Tarapore, P; Fukasawa, K (1999. )Centrosome hyperamplification in human cancer: chromosome instability induced by p53 mutation and/or Mdm2 overexpression.Oncogene, ,18 (11 ),1935-44

Tarapore, P; Richmond, C; Zheng, G; Cohen, S B; Kelder, B; Kopchick, J; Kruse, U; Sippel, A E; Colmenares, C; Stavnezer, E (1997. )DNA binding and transcriptional activation by the Ski oncoprotein mediated by interaction with NFI. Nucleic acids research, ,25 (19 ),3895-903

Tarapore, Pheruza; Hennessy, Max; Song, Dan; Ying, Jun; Ouyang, Bin; Govindarajah, Vinothini; Leung, Yuet-Kin; Ho, Shuk-Mei (2017. )High butter-fat diet and bisphenol A additively impair male rat spermatogenesis.Reproductive toxicology (Elmsford, N.Y.), ,68 ,191-199

Ho, Shuk-Mei; Rao, Rahul; To, Sarah; Schoch, Emma; Tarapore, Pheruza (2017. )Bisphenol A and its analogues disrupt centrosome cycle and microtubule dynamics in prostate cancer.Endocrine-related cancer, ,24 (2 ),83-96

Zhou, Zilan; Kennell, Carly; Lee, Joo-Youp; Leung, Yuet-Kin; Tarapore, Pheruza (2017. )Calcium phosphate-polymer hybrid nanoparticles for enhanced triple negative breast cancer treatment via co-delivery of paclitaxel and miR-221/222 inhibitors.Nanomedicine : nanotechnology, biology, and medicine, ,13 (2 ),403-410

Smithrud, David B; Powers, Lucas; Lunn, Jennifer; Abernathy, Scott; Peschka, Michael; Ho, Shuk-Mei; Tarapore, Pheruza (2017. )Ca2+ Selective Host Rotaxane Is Highly Toxic Against Prostate Cancer Cells.ACS medicinal chemistry letters, ,8 (2 ),163-167

Tarapore, Pheruza; Hennessy, Max; Song, Dan; Ying, Jun; Ouyang, Bin; Govindarajah, Vinothini; Leung, Yuet-Kin; Ho, Shuk-Mei (2016. )Data on spermatogenesis in rat males gestationally exposed to bisphenol A and high fat diets.Data in brief, ,9 ,812-817

Book Chapter

Ho SM, Tarapore P, Lee MT, Leung YK. (2013 )Chapter 14: Biology and Clinical Relevance of Estrogen Receptors in Prostate Cancer Prostate Cancer .(pp. 383-419).Springer New York,(Co-Author)

Ho SM, Cheong A, To S, Janakiram V, Tarapore P, Leung YK. (2015 )Chapter 15: Cancer and DOHaD- Epigenetic reprogramming as a mediator. The Epigenome and Development Origins of Health and Disease.

Post Graduate Training and Education

1998-2001 Postdoctoral Research Assistant (Mentor: Dr. Kenji Fukasawa), Department of Cell and Cancer Biology, University of Cincinnati College of Medicine, , ,Cincinnati, OH

Professional Affiliation

Cincinnati Cancer Center Cincinnati

Contact Information

Academic - University of Cincinnati
Department of Environmental Health
Cincinnati  Ohio, 45267-0056
Phone: 5135585148
tarapopp@ucmail.uc.edu