Element X (Fundamental Discovery)

Element X: a foundation in landmark studies at Stanford. Over the years, landmark studies at Stanford have greatly advanced our knowledge of stem cells. Even prior to the establishment of the CIRM, fundamental discoveries in basic science distinguished Stanford as an early leader in the field. Stanford was the site where mouse and human tissue (adult) stem cells of the blood-forming system were first prospectively isolated (meaning the stem cells were isolated by physical properties before they differentiate), thus maintaining their ability as a therapeutic and prompting early phase clinical trials. Subsequently Stanford researchers built on these successes to prospectively isolate muscle stem cells, and participated in the first prospective isolation of human brain stem cells, which are also currently in early phase clinical trials. Researchers at Stanford were also among the pioneers in discovering the signals that stem cells use to regulate their fate (such as whether to self-renew, differentiate, or die). Also, Stanford researchers provided the foundation for our current understanding of human cancer and the role of cancer stem cells in cancer and pre-cancer development. The discoveries that have distinguished Stanford as a world leader in stem cell biology were based on a unique set of enabling technologies. The more recent developments of hESC technologies are opening new areas of research in brain, muscle, liver, pancreas and other organ systems. Stanford is outgrowing many of the stem cell oriented services that are used to identify and track stem cells. Lokey Stem Cell (SIM1) answers this need with a targeted expansion of core services.

The discoveries described above, and others at Stanford, illustrate the fundamental tenets of human development and the central role of stem cells in human biology and medicine. Stem cell approaches to development and tissue homeostasis (and regeneration), as well as cancer development, are a fundamentally new way of thinking – not covered by classical embryology, developmental biology, or developmental genetics. Stem cell biology in essence comes from the recognition that stem cells differ from all other cells in their respective tissues – they alone can both self-renew and differentiate. Thus, this property insures that stem cell divisions maintain a healthy stem cell pool; progeny cell divisions lead inexorably to the mature cells of the tissue, and without stem cells their failure to self-renew would eventually lead to tissue failure. Stem cells can be genetically marked, prospectively isolated, or in some cases, derived by a special type of cell culture. These fundamental discoveries require scientists with innovative ways of thinking about human development and the unique functions of stem cells in each organ system. SIM1 provides centralized laboratory space to group both existing and new investigators in a facility that is purpose-built to support these efforts.

The strengths of Stanford University in laying the foundation for stem cell research, through the SISCB/RM, have been rewarded with numerous grants from CIRM during the first rounds of research awards. In fact, Stanford has received more CIRM awards than any other institution in California (in all categories including the SEED, comprehensive, small facilities, and new faculty categories). Moreover, we have submitted additional applications to support derivation of novel pluripotent human stem cell lines and to establish premiere disease-specific research groups. Now, we intend to capitalize on our successes and establish a multi-disciplinary, freestanding SISCB/RM with a focus on the following four key areas of stem cell biology in Element X to be housed in SIM1:

  • Human embryonic stem cells [hESCs]
  • Nuclear reprogramming to produce “patient-specific” pluripotent stem cells [NRPSC]
  • Mature tissue or organ stem cells [TSCs]; also termed “adult” stem cells
  • Cancer stem cells [CSCs]

These four areas of concentration in Element X leverage our extensive experience in model systems and hESCs to fuel further discoveries in the basic biology of stem cells. We expect that SIM1 will facilitate the translation from basic to clinical science by providing an environment where it will be possible to purify and isolate the relevant types of stem cells; to analyze their genes, gene programming and proteins; and to find mechanisms for their self-renewal (regulated in normal stem cells, poorly regulated in disease and cancer stem cells). For example, central to our effort to understand the human stem cell, we have established one of the most useful animal models in stem cell biology as a model for the behavior of stem cells taken from normal or neoplastic human tissues, derived from hESCs, or reprogrammed adult cells. In these mice carrying human stem cells, we can test our preclinical approaches for using cells, antibodies, proteins, regulatory RNAs, drugs, and other approaches for efficacy. Furthermore, SIM1 will also provide resources required to work with rare stem cells. Because only small numbers of stem cells can be isolated and transferred, faculty in the SISCB/RM depend on the expertise of our colleagues in physics, engineering, and imaging. Innovations in these areas of science have led to methods to analyze rare cells in the Petri dish and even in living animals. The programmatic integration of bioengineering expertise and the adjacency of SIM1 to the School of Engineering maximize this valuable aspect of our program in SIM1. Leadership of the SISCB/RM program areas of focus is shown:

 
SISCB/RM

Director:Irving Weissman, MD
Deputy Director: Michael Longaker, MD, MBA

Director of Finance & Administration: Lang-Anh Pham
Associate Director of Finance & Administration: Laura Butler

Program Management (8)    Grants Management (4)    Faculty Affairs (1)
Human Resources (2)      Information Technology (1)
Embryos & hESC Reprogramming Adult Stem Cells Cancer Stem Cells

Leader:
Renee Reijo Pera, PhD

Leader
TBN

Leader
Irving Weissman, MD

Leader
Michael Clarke, MD

CIRM Element X Co-Leader:
Roel Nusse, PhD
Co-Leader:
Joanna Wysocka, PhD
Co-Leader:
Theo Palmer, PhD
Co-Leader:
Philip Beechy, PhD
CIRM Element Y Co-Leader:
Seung Kim, MD, PhD
Co-Leader:
Thomas Sudof, MD
Co-Leader:
Judith Shizuru, MD
Co-Leade:
Irving Weissman, MD
CIRM Element Y Co-Leader:
Robert Robbins, MD
Co-Leader:
Michael Longaker, MD, MBA
Co-Leader:
Gary Steinberg, MD
Co-Leader:
Beverly Mitchell, MD

Our research in Element X is recognized both by our many ‘firsts’ in stem cell biology and their applications to biomedicine and human health. SIM1 enables the expansion of both proven technologies as well as a place where novel inventions and applications can occur with maximum efficiency and speed. Our accomplishments give confidence that we can effectively expand translation of discoveries in Element X to Elements Y and Z.

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