Pheruza Tarapore

University of Cincinnati, Department of Environmental Health. 

Welcome!                                                           

RESEARCH:

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) responsible.

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.  

The centrosome organizes 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. Thus, it plays a major role during cell division. Without the centrosome, normal division of human cells could not occur. The centrosome itself has to duplicate once during a cell cycle. If this centrosome regulation is disrupted, it can result in generation of extra centrosomes. The presence of multiple copies of centrosomes can lead to formation of multiple mitotic spindles, disrupt the process of proper separation of chromosomes into daughter cells, and thus result in either loss or gain of extra copies of chromosomes per daughter cell. This chromosomal instability plays an important role in cancer development, acting as an aggressive force for acquisition of more malignant characteristics. Centrosomes have recently gained importance because of their potential role in carcinogenesis. Chromosome missegregation (aneuploidy) in human malignant tumors could arise from abnormally amplified centrosomes. Aneuploidy is a hallmark of cancer cells, which promotes multi-step carcinogenesis by facilitating the mutations responsible for malignant phenotypes. 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. Centrosome hyperamplification is common in human tumors, including breast carcinomas, and is believed to play a critical role in malignant development of tumors. There are control mechanisms that ensure the coordinated progression of centrosome duplication and other cell cycle events, and limit centrosome duplication to once per cell cycle. Deregulation of these controls results in centrosome hyperamplification as seen in cells lacking functional tumor suppressors such as p53 and BRCA1, or on exposure to EDCs such as Bisphenol A.

Selected Publications

Interesting links

List of Journals                     

Indiaindia                    http://homepages.uc.edu/~tarapopp/farohar1.gif            Cincinnati            

 

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