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.

Both children and adults suffer from diseases of their intestinal tract that often lead to small bowel tumors, inflammatory bowel diseases or absorptive impairments. Correction of many of these diseases has often relied on transplantation of healthy small intestine to replace the diseased intestine, however the number of patients requiring transplants far exceeds the number of organs available. Recent advances in stem cell biology may provide alternatives to restoring bowel function in this population.

Gerhard Bauer Laboratory, University of California, DavisEpidermolysis bullosa (EB) is a genetic disease in which the skin is not properly anchored to the underlying layers resulting in blister formation due to minor mechanical friction. There are many different manifestation of EB, ranging from mild to lethal. Recessive dystrophic EB, one of the most severe manifestations of this disease is a result of a mutation in the COL7A1 gene which prevents the production of functional collagen 7, a crucial protein in anchoring the basal lamina of the skin to the dermis and epidermis.

When human skin is severely wounded, the repair mechanism is notoriously inadequate. The superficial layer, called the epidermis, can re-grow but the underlying tissue, called the dermis, doesn’t remodel and the result is scar tissue. Scar tissue is skin that lacks epithelial appendages (e.g., sweat glands, hair follicles (HF)). Several Wnt genes have been shown to be expressed during wound healing leading to speculation that Wnt factors could be used to stimulate skin healing.

The current treatment for end stage liver disease is organ transplantation. The number of patients in need of a liver transplant far out weights number of donor livers available. Transplantation of hepatocytes from donor livers has been shown to correct liver disease in humans. Since human hepatocytes cannot be expanded in culture, this treatment still relies on the inadequate donor liver population. Our goal is to create a cellular therapy to repopulate the liver and rescue it from liver disease.