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).

Spinal cord injury (SCI) results in a long-term functional deficit, as the injured spinal cord fails to connect to their original targets and restore circuitry. After the injury, many spinal cord cells are lost not only in the initial injury, but in the hours, days and weeks following the accident. In particular, neurons are also lost close to the injury site. Valuable therapies are extremely important for curing SCI. The Plant lab focuses on repairing spinal cord injury by performing stem cell and glial cell transplantation into injured spinal cord. These models are both mouse and rat.

For decades, cancer researchers have observed an increased reliance of tumor cells on glycolysis rather than the tricarboxylic acid (TCA) cycle and oxidative phosphorylation. In the context of ATP generation, this observation is counterintuitive, as glycolysis produces significantly lower ATP yields per glucose. However, recent research has indicated that this metabolic shift is beneficial for cancer cells as it shuttles carbon backbones into key anabolic pathways, helping them generate the macromolecular precursors required for rapid growth.

Chronic myocardial infarction (CMI) is the leading cause of death and disability in the U.S. with an estimated 16.3 million individuals suffering from this condition which was responsible for 1 in 6 deaths in the United States in 2007. Current medical and surgical treatments aim to retard the formation of negative tissue remodeling but fail to restore cardiac function. Cell based regenerative therapy for CMI has shown promise but has achieved limited success in the clinic due to poor donor cell retention and survival, and limited interaction with the diseased tissue.