Transcriptional networks regulating luminal environment in the human epididymis.
The human epididymis is a tightly coiled tube with distinct regional properties that forms an essential part of the male reproductive tract. Immature sperm leaving the testis acquire the ability to swim and fertilize an egg during their transit along the epididymis. The epithelial layer lining the male genital ducts has a critical role in normal reproduction and its impairment by disease has a profound effect on fertility. An example is the common inherited disorder cystic fibrosis (CF), in which functional inactivation of the CFTR gene in the genital duct epithelium results in male infertility. The epithelial layer controls the luminal environment in the epididymis that is required for sperm maturation. The goal of this research program is to understand the mechanisms that coordinate the unique properties of the human epididymis epithelium and are pivotal in achieving normal sperm maturation in humans. Though epididymal function has been studied in small and large mammals, much less is known about the human organ and each species is quite different. We are using primary epithelial cell cultures (HEE cells) from the head (caput), body (corpus), and tail (cauda) of the human epididymis. These cells recapitulate the regional distribution of epididymis function.
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Current Projects:
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To determine how unique cell-type specific elements control CFTR gene expression in the caput epithelium.
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How does the Androgen Receptor, together with unique co-factors, controls gene expression in the epididymis?
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How do transcriptional pathways governed by individual transcription factors coordinate ion transport in the human epididymis and thus impact the luminal environment?
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Using single-cell RNA sequencing (scRNA-seq) to define cell types in the human epididymis epithelium.
Recent Publications:
Browne, J.A., Yang, R., Leir, S-H., Eggener, S.E., Harris, A. (2016) Expression profiles of human epididymis epithelial cells reveal the functional diversity of caput, corpus and cauda regions. Molecular Human Reproduction 22:69-82. Epub 2015 Nov 26. PMCID: PMC4733224
Browne, J.A., Yang, R., Leir, S-H., Eggener, S.E., Harris, A. (2016) HNF1 regulates critical processes in the human epididymis epithelium. Molecular and Cellular Endocrinology. 425:94-102 Epub 2016 Jan 22. PMCID: PMC4799753
Browne, J.A., Leir, S-H., Eggener, S.E., Harris, A. (2018) Region-specific Innate Antiviral Responses of the Human Epididymis. Molecular and Cellular Endocrinology. In Press. Epub Jan 13th.