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.

Theo Palmer’s lab focused on the ability of adult neuronal precursors to develop into mature neurons and many focuses particularly on the dentate gyrus (DG) of the hippocampus which among other things has been associated with learning. My work has focused on understanding the interaction between learning and forgetting in particular Rac1 a Rho GTPase protein that has been associated with in neuronal morphogenesis, survival, neural transmitter release, neurogenesis, and neuronal migration and forgetting.

The Stainier lab uses the zebrafish as a model to investigate vertebrate organ development. The lab is interested in understanding molecular events that drive processes such as cellular differentiation and morphogenesis. The zebrafish is an ideal model organism to study early embryological development. It grows quickly and provides clear resolution of single cells in any tissue during all developmental stages. Diabetes is a detrimental disease that affects more and more people each year.

In humans, injuries to the retina can cause irreversible damage that results in vision impairment and blindness. The potential of stem cell-based treatments for these devastating conditions depends upon a detailed understanding of the growth factors and cytokines that maintain retinal homeostasis, and the roles they may play in activating retinal progenitor cells in the mammalian retina. Here, we demonstrate that potentiated Wnt signaling in the mammalian retina results in the increased production of retinal progenitor cells.

Quiescent satellite cells (SCs) display heterogeneous expression of Pax3 which has been shown to play a role in proliferation and myogenic determination. p53 is known to be involved in the regulation of quiescence, self-renewal, cell fate, and cellular senescence. SCs from the diaphragm lose their myogenic fate at a much higher rate than SCs from the hindlimb. Early results show that p53 displays differential activity in the diaphragm versus the limb SCs. Indeed, when Pax3 is overexpressed in C2C12 cells p53 is destabilized.

Professor Irving Weissman, Stanford University