Dahiya Research Program
NIH/ NCI / UO1CA184966
Genetic factors for race related prostate cancer.
The main goal of this project is to investigate the genetic basis of prostate cancer health disparities. The rationale is that prostate cancer is the leading cancer among men of African descent in the USA. A substantial proportion of African American men have a higher overall incidence, earlier age of onset, increased proportion of clinically advanced disease and increased bone metastases and mortality from prostate cancer compared to Caucasians. Based on our preliminary data, we hypothesize that the differential expression profile of a set of oncogenic miRNAs and tumor suppressor miRNAs in African Americans may target a set of prostate cancer specific genes and may contribute to the prostate cancer health disparity in African Americans. The molecular mechanisms of action of tumor suppressor miRNAs are through repressing oncogenes and activating tumor suppressor genes. We will test these hypotheses through analyses of a series of experiments proposed under our specific aims. All the aims are highly focused, centralized, innovative, clinically significant, functional and mechanistic in nature.
NIH / NCI / RO1CA199694
Molecular biomarkers for kidney cancer prognosis using non-coding RNAs.
We will investigate the functional significance of non-coding RNAs in kidney cancer using both in vitro and in vivo models. We will also investigate the molecular mechanisms of action of non-coding RNAs through binding to PCR2 that in turn modulates histone modification complexes, activates EMT genes and induces kidney cancer progression. The proposed concepts, methods and technology will advance the field of non-coding RNAs as genetic biomarkers and potential therapeutic targets for the management of kidney cancer.
Regulation of c-myc/HIF pathway in the management of kidney cancer. VA Merit Review BX001123
The main goal of this project is to investigate the role of miRNAs in targeting c-Myc/HIF pathway and thus suppress kidney cancer progression and metastasis using both in vitro and in vivo models. Accomplishment of this project will be a significant step forward in understanding miRNA-mediated suppression of c-Myc/HIF pathway and designing novel miRNA-based therapeutic strategies for inhibition of progression and metastasis of kidney cancer among our Veterans.
Title: Wnt antagonist genes in kidney cancer progression and metastasis
The main goal of this project is to investigate the role of Wnt antagonist genes in the progression and metastasis of renal cancer. Three specific hypotheses will be tested to determine if: 1) inactivation of Wnt antagonist genes is involved in the progression and metastasis of kidney cancer; 2) the mechanisms of inactivation of the Wnt antagonist genes are through epigenetic pathways such as DNA methylation, histone modification and chromatin remodeling; 3) transfection of Wnt antagonist genes suppresses the in vitro and in vivo growth and metastasis of kidney cancer. Successful completion of the proposed experiments may provide us with better strategies for the management of kidney cancer.
Title: MicroRNAs in the progression and metastasis of prostate cancer
The main goal of this project is to investigate the role of a set of microRNAs (miRNAs) in the progression of prostate cancer. Aim 1 will investigate the expression of a set of miRNAs in human prostate cancer tissues and also analyze whether miRNAs can regulate cell proliferation and progression using prostate cancer cell lines. Aim 2 will investigate the molecular mechanisms of microRNA inactivation in prostate cancer cells. Aim 3 will investigate whether microRNAs can inhibit growth and proliferation of human xenograft prostate tumors in a nude mouse model. To validate our in vitro results, we will also use an in vivo model of mouse xenografts with human prostate cancer cells. Successful completion of these experiments will demonstrate the functional role of specific microRNAs in the suppression of prostate cancer growth and also the mechanism of inactivation of these genes in prostate cancer.
Title: Chemo-dietary prevention, miRNAs, epigenetic and prostate cancer
The main goal of this project is to investigate whether dietary isoflavones such as genistein can inhibit prostate cancer growth through activation of tumor suppressor microRNAs (miRNAs) using both in vitro and in vivo models. Aim 1 will test the hypothesis that genistein-mediated activation of tumor suppressor microRNAs is involved in the regulation of prostate cancer. Aim 2 will test the hypothesis that DNA methylation and histone modifications are the key mechanisms of genistein-mediated activation of microRNAs in prostate cancer. Aim 3 will test the hypothesis that genistein can suppress prostate cancer growth in a nude mouse model through activation of microRNAs. Impact: The project will provide a novel paradigm with high impact in the field of management of prostate cancer, since dietary-mediated activation of tumor suppressor miRNAs and their roles in the inhibition of prostate cancer progression have never been investigated.
VA Merit Review 1I01BX001123-01 Department of Veterans Affairs
Title: Genistein, microRNAs and kidney cancer
Renal cell carcinoma (RCC) is one of the most common malignancies among our veterans. The major barrier to progress in the management of RCC is the high toxicity of the drugs used for treatment. The present proposal will help to address this problem by utilizing dietary methods for the management of RCC, using in vitro and in vivo models. The main goal of this project is to investigate whether genistein can inhibit kidney cancer growth through activation of tumor suppressor microRNAs (miRNAs) using both in vitro and in vivo models. Since the goal of this proposal is to investigate the dietary-mediated inhibition of RCC through activation of tumor suppressor miRNAs, we believe that the work proposed is highly relevant to veterans’ health and the VA mission.
VA Program Project, Center for Excellence, Department of Veterans Affairs
Title: Role of genetic biomarkers in clinical assessment of prostate cancer
The overall goalof this project is to identify genetic biomarkers that can be of use in risk assessment of prostate cancer. The hypothesis is that identification of a set of genetic factors can be useful and beneficial in the risk assessment of prostate cancer. There are three specific projects under this program. We expect that the combination of miRNAs, SNPs of MMR genes, and TSPX will be useful genetic biomarkers for the clinical assessment of prostate cancer. Therefore, all the projects are highly inter-related, centralized and focused. Analyses of these genetic biomarkers will achieve objectives greater than the sum of the individual results from the three projects. MiRNAs, SNPs and X chromosome-linked genes are novel genetic biomarkers and collectively, they can provide us with valuable information to better manage localized prostate tumors that are likely to progress and metastasize. Clinical Relevance: Prostate cancer is the most common male malignancy among our veterans and is designated as a high priority research area. This program project will directly impact veterans’ health care, since we propose to identify genetic biomarkers that can be utilized for risk assessment of prostate cancer.