Increasing evidence suggests cell-to-cell communication is possible via extracellular RNAs (exRNAs). Regulation of gene expression through microRNAs (miRNAs) has long been established as an endogenous mechanism for fine-tuning expression post-transcriptionally. These small RNAs can prevent translation by binding to the 3’-UTR (untranslated region) of a target mRNA transcript. Recently, many studies have suggested miRNAs can act intercellularly (as exRNAs), potentially broadening their role in many biological processes.

Genome editing is one of the forefront topics of science with vast potential uses. One large application is the effects that precise genome editing will have on the field of regenerative medicine. Precise genome editing for therapeutic purposes is difficult to achieve because it requires the pathway of homology directed repair (HDR) to be active rather than non-homologous end joining (NHEJ) which results in deleterious insertions or deletions in the DNA. These pathways are distinct and are regulated by different enzymes.

A heterozygous missense mutation in the H3F3A gene, which encodes a lysine-27-to-methionine substitution in the replication-independent histone H3.3, has been implicated as the main tumor driver in a subset of pediatric high-grade gliomas. This mutant histone variant, H3.3-K27M, alters normal histone marks and promotes a globally hypomethylated DNA landscape. Recent evidence has led to speculation that this mutation promotes gliomagenesis, exclusively, in oligodendrocyte progenitor cells (OPCs) to form diffuse intrinsic pontine gliomas (DIPGs).

Lethal Giant Larvae (Lgl1) is a protein involved in establishment of cellular polarity and is implicated in numerous cancers by expression or splicing aberration. Studies in the brains of mammalian models have shown protein knockout results in lesions exhibiting overproliferation and differentiation defects reminiscent of neoplasm. Our lab is examining the role of Lgl1 in regulation of key components of tissue homeostasis with emphasis on oligodendrocyte precursors.

Little is known about the growing number of gene mutations implicated in Autism Spectrum Disorder (ASD). Their mutations need to be studied in order to predict in vivo effects. We hypothesize that mutations found in ASD genes will cause dysregulation of GABAergic interneuron development. The aim of this project is to utilize a moderate throughput assay to identify in vivo functional changes that are caused by nonsynonymous mutations in candidate ASD genes. We will focus on CNTNAP2, an ASD susceptibility gene that has multiple mutant alleles that were identified in ASD populations.

Planar Cell Polarity (PCP) is required for proper orientation of a cell within a tissue and organ during development and regeneration. PCP has been described in adult neurons but its role during neuronal differentiation remains enigmatic. During postnatal cerebellum development granule neural precursors (GNPs) proliferate on the surface in the external granule layer, then start to migrate inward in a directed way to later form granule neurons (GN), the most abundant cell type in the brain.

The Reijo Pera Laboratory investigates a range of areas including germ cell and embryo development, sex-linked developmental disorders, degenerative diseases like Parkinson’s and urinary incontinence. The project I work on focuses on the differentiation of human Embryonic Stem Cells (hESCs) to smooth muscle cells for the treatment of Stress Urinary Incontinence. This condition is predominantly caused by loss of function in the urethral sphincter, which is often a result of pregnancy, childbirth, and aging.

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder afflicting nearly one in 10,000 people in the United States. Linked to expanded trinucleotide repeats in exon 1 of the huntingtin gene, HD causes death in 100% of those afflicted through an accumulation of protein aggregates and aberrant gene regulation. The disease is characterized by neuronal atrophy of the striatum which results in uncontrollable bodily movements, aggression, cognitive decline, and psychosis.

Adult neurogenesis is a highly regulated process through which the adult mammalian brain produces new neurons. Understanding the factors that regulate this process is important to our general knowledge of the adult brain, as well as neurodegenerative or neurological disease. Previous studies show that vascular endothelial growth factor (VEGF) enhances neural progenitor cell proliferation, both in vitro and in vivo.

My work as a CIRM bridges scholar focuses on the intestinal stem cell (ISC) niche. The surfaces of the intestine and colon are covered in a highly regenerative epithelial layer, which rapidly renews itself in response to mechanical and chemical damage. This renewal is affected by a stem cell population that resides in small invaginations of the intestine known as crypts. Crypt base cells presenting the g-protein couple receptor Lgr5 are thought to represent the actively cycling stem cells and have been shown to repopulate the intestinal epithelium in a clonal manner.