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Gene X Environment Control of Neuroendocrine Mechanism of Reproduction:Exposure Assessment Biomarkers for Complex Diseases

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

About This PhD Project

Project Description

Findings of the potential adverse effects of endocrine disrupting compounds (EDCs) have increased both scientific and environmental public health concerns regarding the widespread use of pesticides, fertilizers, pharmaceuticals and naturaceuticals. Studies have reported that these chemicals and drugs, alone or in combination, produce deleterious reproductive health effects. Their complex mixture exposure to neuroendocrine mechanisms have shown effects on precocious puberty and cancer of reproductive origin including, breast, ovarian and endometrial cancer. Elucidation at the neuroendocrine level of complex mixture exposure on gene X environment (G x E) interactions and its association with disease etiology will help develop environmental and epigenetic biomarkers of reproductive impairment, aging and complex diseases.
My research focus is on understanding the influence of complex mixture exposure on upstream regulation (e.g., via various Kisseptin, GABA and other neurotransmitters) of Gonadotropin-releasing Hormone-II (GnRH-II) release and cellular signaling on its downstream role in precocious puberty, reproductive aging, obesity related hypogonadism and cancer. This will be achieved by a combination of meta-selection of candidate biomarkers and their further validation in cell culture, animal and in human studies. My research will potentially lead to the:
• Identification of complex mixture exposure assessment biomarkers of G x E interactions
• Development of environmental and epigenetic biomarkers of precocious puberty, reproductive aging, metabolic disorders, obesity and cancer
• Discovery of theranostic candidate(s) of G x E interactions in complex diseases etiology

References

1. Alok Deoraj, Harshath Gupta et. al. 2013. Oncogenes and their interaction in response to environmental chemical exposures, proceedings of the American Public Health Association annual Meeting held in Boston, MA, Nov 2013.

2. Victor Okoh, Alok Deoraj, Deodutta Roy. 2011. Estrogen-induced reactive oxygen species (ROS)-mediated signaling pathways contribute to breast cancer. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 1815(1):115-133

3. Alok Deoraj, Deodutta Roy. 2010. Approaches to identify environmental and epigenomic components or covariates of cancer and disease susceptibility and their Interactions with genes. In: Environmental Factors, Genes, and the Development of Human Cancers. Eds. Deodutta Roy and Dorak M. Tevfik. Springer USA. 197-207.

4. Deoraj Alok, R. Sampath Kumar, John M. Trant and Yonathan Zohar. 2001. Recombinant perciform GnRH-R expressed in a fish and mammalian heterologous cell lines activate differential signaling. Comparative Biochemistry and Physiology. 129: 375-380.

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