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.

In 2006, Shinya Yamanaka described a method for reprogramming fibroblasts to embryonic stem cells by defined factors, termed induced pluripotent stem cell (iPSC) reprogramming. Since then, iPSC have been achieved by other methods to include mRNA transfection and episomal expression vectors that rely on application of exogenous nucleic acids. mRNA based reprogramming is desirable for its non-integrating approach and versatility in daily mRNA dosing that may be finely tuned to overcome experimental challenges with potential gains in iPSC quality and efficiency.

When skeletal injury occurs, osteogenic stem cells, residing in the bone marrow, are responsible for the regeneration of new bone. Aging negatively impacts this process. As we get older, bone reabsorption predominates and commonly manifests as osteoporosis or a non-healing fracture. Based on the fact the Wnts signals are critical regulators of bone formation, we hypothesize that promoting Wnt signaling in aged patients will stimulate bone healing. A novel method of packaging Wnt protein into liposomes (L-Wnt3a) has been developed recently to allow the direct test of this hypothesis.

The cancer stem cell hypothesis represents a paradigm-shifting concept in tumor therapy resistance. This small population of tumor initiating cells is relatively quiescent. This makes them resistant to conventional cytoreductive cancer therapies such as radiation or chemotherapy which seek to damage the DNA of dividing cells. It is these cancer stem cells that may provide a major mechanism for cancer relapse and therapeutic resistance.

For the next year I will be a working member in the laboratory of Dr. Ebenezer Yamoah at the Center for Neuroscience at UC Davis. I will be joining an ongoing project to repair damaged or lost inner hair cells of the cochlea. Induced by mechanical stimuli, these hair cells promote an electrical signal routed to the brain by spiral ganglion neurons, a process that is essential for functional hearing. Neural stem cells, located in the subventricular zone of the lateral ventricle, readily differentiate into bipolar neurons.

Animal and cellular models have been developed to study neurodegenerative diseases, but do not always epitomize the pathology of human diseases. While some insight into neurodegenerative disorders and their cellular mechanisms has been gained from the study of post-mortem human brain tissue, this source does not dynamically represent disease pathogenesis.Patient-specific induced pluripotent stem cells (iPSC) recapitulate the genotype and phenotype of their parental somatic cells and can be used to model disease in vitro.

The Longaker lab is a reconstructive plastic surgery lab focusing on skeletal and epithelial reconstruction and regeneration. I am working with the skeletal biology and bone team, under the guidance of Dr. Natalina Quarto. My project is primarily an investigation into the effects of Twist1 haploinsufficiency on calvarial development and regeneration. In a normal skull, Twist1 is expressed in the mid-sutural mesenchyme. Although Twist1 does not affect the expression of the master osteogenic gene Runx2, it does inhibit transactivation of the gene by binding to the DNA binding motif of Runx2.

Recent advances in human germ cell derivation have resulted in the production of male and female gametes from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) in vitro. So far, this process has been relatively inefficient as compared to gametes derived from mouse ES cells. To better understand the developmental pathways that result in the production of germ cells in vivo, we seek to model germline derivation by recapitulating some of the cellular and signaling events in an in vitro platform.