Stem Cell Research at Salk
There are currently 14 principle investigators who are devoting part of their research to stem cells at the Institute. Here are brief summaries of what each is working to accomplish in their labs.
Juan-Carlos Izpisúa Belmonte studies the reprogramming process in murine and human germ stem cells, which spontaneously transform into pluripotent embryonic stem cell-like cells when placed in lab dishes. Since these cells don't require any outside help to override internal growth controls, they are less likely to start dividing uncontrollably.
Senyon Choe tries to identify therapeutically useful messengers molecules involved in hESC self-renewal and maturation to realize the full clinical potential of stem cell therapy.
Beverly Emerson suggests that genes are arranged in "neighborhoods" that are surrounded by "fences" that protect the activity in one neighborhood from spilling over into adjacent territory. She wants to identify the fence(s) that border genes that are important to maintain stem cells in their most plastic state.
Fred H. Gage and lab members have developed protocols that stimulate hESCs to develop into neural stem cells that can then develop into dopamine neurons or cholinergic motor neurons. He will use these cells to explore the cellular and molecular causes for the dysfunction and death of dopaminergic or cholinergic neurons in Parkinson's disease or Amyolateral Sclerosis (ALS), respectively.
Kathy Jones studies how transcription elongation and histone methylation factors function to promote stem cell proliferation, which will help future efforts to direct these cells towards specific developmental fates.
Leanne Jones seeks to uncover the mechanisms that regulate the process of de-differentiation or reprogramming and to compare these to the mechanisms that endow stem cells with their ability to self-renew. Reprogramming of specialized cells could provide a "reservoir" of cells that could act to replace stem cells lost due to wounding or aging.
Jan Karlseder is interested in how telomeres, the protective "caps" at the end of all 46 human chromosomes, are maintained in stem cells and how this mechanism is disabled once stem cells differentiate.
Kuo-Fen Lee investigates the role of stem cells in neurodegenerative diseases. He uses neurons derived from human or mouse embryonic and neural stem cells to study genetic and epigenetic mechanisms underlying the formation of synapses, the connections between nerve cells.
Satchin Panda's work on circadian rhythms has led him to the question of how soon the internal circadian clock starts ticking in developing embryos. He will start his search for cells ticking in unison in stem cells.
Samuel Pfaff wants to discover the molecular signals that coax stem cells to develop into motor neurons, which control our ability to walk, to talk, to breath or swallow. Over the long term, he hopes to identify small molecule drugs that can help the process along.
David Schubert uses human neuronal stem cells to identify both the molecules and the molecular pathways that lead to the differentiation and growth inhibition of human stem cells. The latter is important to prevent embryonic stem cells from turning cancerous, a lethal property they all share.
Wylie Vale and his colleague Peter Gray focus on cripto, the founding member of a small family of vertebrate signaling proteins that function in development. Cripto is highly expressed in hESCs, where it appears to act as an essential cofactor for the maintenance and directed differentiation of these cells.
Inder Verma's current main focus is the reprogramming of human skin fibroblasts into hepatic stem cells and their subsequent differentiation into liver cells.
Lei Wang plans to introduce non-natural amino acids to identify unknown factors that govern the development of stem cells into dopamine neurons. Uncovering the mechanisms that regulate the differentiation of embryonic stem cells into dopamine neurons may yield new drug targets and inspire novel preventative or therapeutic strategies for Parkinson's disease.