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.

The Calos Lab is focused on developing a combined gene therapy and stem cell therapy technique in order to treat Duchenne Muscular Dystrophy (DMD). DMD is a common and fatal genetic disease caused by a mutation in the dystrophin gene. We are seeking to reprogram fibroblasts from afflicted patients and correct the disease by addition of functioning dystrophin. Using a bacterial integrase known as PhiC31, we are inserting a removable reprogramming cassette and the therapeutic gene stably into the genome.

The Weaver lab is multi-disciplinary lab dedicated toward understanding the role of mechanical force on breast cancer progression and human embryonic stem cell (hESC) differentiation. Forces exerted upon and by the cell are mediated by the extracellular matrix (ECM), which varies in structure and stiffness throughout the body. Most cell culture work is done on tissue culture plastic which is several orders of magnitude stiffer than physiological ECM stiffness.

The Palmer lab examines neural stem cells in development and in the adult brain. The lab has been able to reconstruct the conditions of neurogenesis in the Petri dish. Their studies of stem cells in the adult focus on the hippocampus, an area of the brain where neurogenesis naturally continues throughout life. The generation of new neurons within the hippocampus is mediated by proliferating neural stem or progenitor cells (NPCs). NPCs in the mammalian central nervous system have the ability to self-renew as well as differentiate into mature neurons.