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.

Cancer stem cells (CSC) are a subpopulation of cells residing within a tumor that are hypothesized to be responsible for tumor initiation, metastasis, and recurrence. These cells have stem-cell-like characteristics including the capability to self-renew, be in a quiescent state, and be capable of long-term clonal repopulation. Increased stress, hypoxia and inflammation have been demonstrated to induce a plastic phenotype for CSCs, allowing for either tumor growth or tumor escape.

Coronary heart disease is a leading cause of death in the United States. Current therapies only slow disease progression with heart transplantation being the only curative option. This project proposes to use an extracellular matrix (ECM) device to deliver mesenchymal stromal cells (MSC) to damaged cardiac tissue after myocardial infarction in order to regenerate and restore its function. My project aims to prove that seeding MSCs on matrix alters chemotactic cytokine secretion in a manner that is beneficial for the MSCs and surrounding target tissue.

Stem cell based therapies are a promising treatment option for patients who suffer from extensive burns or genetic skin diseases such as Dystrophic Epidermolysis Bullosa. Differentiating epidermal cells requires understanding of molecular signals, gene expression patterns and transcriptional regulatory networks involved in skin development. Developmental regulation is influenced by both coding and non-coding genes. Long non-coding RNAs (lncRNAs) resemble mRNA transcripts yet are not translated to proteins.

The clinical problems relating to the skeleton (bone, cartilage and bone marrow stromal niche) could be ultimately addressed by a thorough understanding of how the skeleton develops and is maintained from a stem cell point of view. By identifying and characterizing the human skeletal stem cell (hSSC) and its downstream progenitors, novel cell-based therapies can be developed for treating conditions affecting the bone marrow stromal niche. We seek to define the cellular origins of skeletal tissues to study how the human skeleton is formed and maintained throughout life.

Recent studies have shown an upregulation of Wnt expression in a number of different tissues following injury. A novel injury responsive enhancer, which we refer to as CAIRE (cis-acting injury response element), is proposed to regulate the transcriptional activation of Wnts following injury in multiple tissues. A key question in the role of CAIRE is which transcription factors (TFs) bind to CAIRE. In order to address this question, we are using a two-pronged approach to both identify candidate TFs and to verify their role in CAIRE activation in vitro.

The human endometrium, the prerequisite for a successful pregnancy, is cyclically regenerated by stem and progenitor cells according to local steroid hormone concentrations. Endometrial mesenchymal stem cells (eMSCs) are the adult stem cell population responsible for maintenance of the endometrium and have recently been characterized as pericytes (Spitzer et al 2012). Research has demonstrated that adult stem cell populations remain in a quiescent state until stimulated by tissue damage or remodeling signals (Venezia et al 2004).