Nehemiah Alvarez, PhD
Research Assistant Professor
Molecular & Integrative Physiology
PhD, University of Kansas Medical Center
In mammals, only 2-5% of the genome contains exon sequences. Conversely, nearly 50% of the genome is composed of transposable elements. Transposable element sequences are derived from viral infections that were captured by the host genome. Integration of transposable events can have an important impact on the genome and on organismal physiology. In some cases, integration of transposable elements may cause DNA damage and mutagenesis, but it may also result in the introduction of sequences that can recruit transcription factors and result in the rewiring of transcriptional networks. Integration events can also occur within protein coding exons, generating proteins of altered function. Lastly, integration of transposable elements can result in the preservation of the viral open reading frames, resulting in the expression of full-length viral proteins. This is a particularly important point, because transposable element encoded proteins have the potential to retain many of the multifunctional roles of their viral cousins. These include modulation of signal transduction pathways, attenuation of innate immune signals, and altering translation efficiencies. In most tissues, transposable elements are transcriptionally silenced. Dysregulation of transposable element expression drives inflammatory states, and during pregnancy, inflammation is associated with adverse outcomes. Paradoxically, during pregnancy trophoblast cells are permissive for the expression of transposable elements. Trophoblast lineage differentiation is required for the survival and development of embryos during pregnancy. Defects in trophoblast development can lead to failed pregnancies and other pregnancy related disorders. My research focuses on understanding how proteins encoded by transposable elements function in trophoblast cells during normal and pathological conditions.