In my laboratory we study:

• Innate immunity and antimicrobial properties of male reproductive organs.

• Molecular biology of testicular torsion injury.

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Innate Immunity and Antimicrobial Properties of Male Reproductive Organs
During transit in the male reproductive tract it is critical that sperm are protected from a variety of insults including harmful chemicals and microorganisms such as bacteria, yeast and viruses.  Damage to spermatozoa as a result of bacterial, yeast, and viral infections of male reproductive organs is known to contribute to reduced fertility or infertility.  

My research has focused on the molecular mechanisms used by the testis and other reproductive organs to protect cells in these organs, including sperm, from microbial pathogens.  Previously we have studied inflammatory and hormonal mechanisms in the epididymis that regulate mRNA expression for members of the defensin family of antimicrobial peptides and we have investigated the role of Toll-like receptors (TLRs) in innate immunity of male reproductive organs. 

TLRs are important mediators of “pathogen-sensing” in innate immune responses and inflammatory actions and they also play critical roles in adaptive responses to microbial challenge. TLRs comprise a large, evolutionarily conserved family of receptors that mediate innate immunity in a wide range of organisms. Signal activators for TLRs include both gram-positive and gram-negative bacteria, as well as bacterial components including bacterial flagellin, lipoproteins, peptidoglycans, CpG bacterial DNA, and lipopolysaccharides (LPS).

In 2010, initial work from our lab on the characterization of TLRs in the male reproductive tract  published with undergraduate student co-authors (Biol. Reprod., 76:958-964, 2007) was recognized as one of the most highly cited papers in Biology of Reproduction for 2007-08.  Recently we have been examining the effects of LPS-induced inflammation of the testis on the up-regulation of hypoxia-inducible factor-1 and the crosstalk between inflammatory pathways and hypoxia pathways in the testis.

 

 

Molecular Biology of Testicular Torsion
Testicular torsion is a medical emergency that results from a twisting of one testis or both testes around the spermatic cord.  Even with prompt diagnosis and relief of torsion, most patients suffer from impaired reproductive function due to damage of the salvaged testis caused by ischemia (decreased blood flow) and resulting hypoxia (decreased oxygen concentration) in the affected testis.  Germ cell-specific apoptosis is one form of testis damage that occurs following ischemia and ischemia-reperfusion injury.  We use a rodent model of torsion of examine molecular responses to oxygen imbalance in the testis.

In many tissues, hypoxia-inducible factors have been identified which regulate molecular responses to hypoxia.  Hypoxia-inducible factor-1 (HIF-1) is a key regulator of the cellular response to hypoxia.  HIF-1 is a transcription factor primarily expressed when mammalian cells are subjected to hypoxia.  HIF-1 activates transcription of genes that are important for maintaining oxygen homeostasis.  Our hypothesis is that HIF-1 may play important roles in antiapoptotic responses to protect Leydig cells from hypoxia during testicular torsion injury.  The focus of this research is to gain a better understanding of the molecular events involved in torsion-induced damage of the ischemic testis and the regulation of oxygen microenvironments within the testis by studying the roles of testicular HIF-1.