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The overall goal of the California Institute for Regenerative Medicine (CIRM) training program is to
develop creative and productive scholars who bring to their work a thorough understanding of
the biological, engineering, ethical and legal complexities surrounding stem cell research, and a
shared commitment to the application of stem cell biology and engineering to the improvement
of human health. 
Our program provides training for clinical fellows, postdoctoral and pre-doctoral fellows in molecular biology, bioengineering or related scientific disciplines. Clinical fellows are appointed through CHORI, with a focus on post-residency training to expand the clinical applications for cord blood stem cell therapies. Postdoctoral fellows’ primary appointments may be at UC Berkeley, Lawrence Berkeley National Laboratory or at CHORI, and pre-doctoral fellows will be doctoral candidates in any relevant science or engineering department at UC Berkeley. Ongoing areas of study available to CIRM Scholars include molecular mechanisms regulating stem cell pluripotency; differentiation of hematopoietic, neural and mesenchymal stem cells; the molecular basis for the reduction of stem cell regenerative capacity with age; engineering controlled environments for tissue-specific differentiation of hES cells; engineering artificial niches and minimally invasive methodologies to enable or evaluate the results of stem cell transplantation; engineering high throughput devices for cell purification and differentiation protocols; and the use of computational biology and mathematical modeling for deciphering stem cell gene networks. This multidisciplinary training program also includes two pre-JD law fellows and one predoctoral fellow in the social sciences and humanities, to be supported by the Berkeley Stem Cell Center. The Berkeley Stem Cell Center's current CIRM Scholars, and their research interests are:
 Morgan Carlson, PhD (Postdoctoral Scholar, Bioengineering, Irina Conboy, mentor)
Successful muscle repair is determined by an antagonistic balance between TGF-beta/pSmad signaling levels and Notch pathway activation, such that activation-inactivation of Notch determines the presence of pSmad3 on the promoters of cyclin-dependent kinase inhibitors. During the aging process, this balance becomes unstable in ways that assure the lack of tissue repair. In order to better understand the aging pathology of these pathways and their components, my work focuses on engineering self-attenuating synthetic circuitries for maintaining TGF-beta/pSmad and Notch signaling homeostasis. These constructs will enable focused expression for tunable attenuation within any specified stem cell subset of interest, thereby helping to harness the regenerative properties of organ stem cells.
 Patrick Goodwill (Predoctoral Scholar,Bioengineering, Steve Conolly, mentor)
Stem cell therapy requires successful delivery of stem cells to the target organ, adherence and survival of these cells in the damaged tissue environment, and ultimately, differentiation into cells of the damaged target organ. At present, there is no reliable way to non-invasively track stem cells in humans or animals. Optical methods cannot penetrate more than a centimeter, even with complex reconstruction algorithms. As a CIRM Scholar, I am developing a new method of stem cell tracking, Magnetic Particle Imaging (MPI). MPI is projected to be 200x more sensitive than MRI, which is currently used to track cells and whose sensitivity is insufficient. My specific aims are to (1) Develop MPI with an emphasis on detecting single tagged cells, and (2) Improve the detection limit of MPI through novel intermodulation methods and by detecting received signal from multiple axes.
Bindu Kanathezhath, MD (Clinical Fellow, CHORI, Frans Kuypers, mentor)
We are investigating a novel method that would facilitate major histocompatibility complex (MHC) mismatched donor umbilical cord blood transplantation by reducing the risks of graft-vs-host disease and graft rejection. We propose to accomplish this by inactivating donor T-cells by photochemical treatment. Viable T-cells are photochemically treated with a psoralen drug, amotosalen (S-59), such that the secretion of T-cell cytokines necessary for engraftment is retained, but proliferation necessary for graft-vs-host disease is blocked. Our preliminary experiments show that stable engraftment of donor cells can be achieved and graft-vs-host disease minimized by co-transplantation of MHC-mismatched T-cell depleted marrow and S-59 treated donor T-cells. If successful in a murine thalassemic model of MHC-mismatched umbilical cord blood transplantation, we believe that this methodology can be translated to the clinic. Thus, the proposed studies have the potential to make this curative therapy available to those who lack suitable donors.
 Lauren Little (Predoctoral Scholar, Chemical Engineering, Kevin Healy, mentor)
Traditionally human embryonic stem cells are cultured on animal extracellular matrix proteins, which allow for cell adhesion, proliferation, and maintenance of self-renewal. Since growing cells on animal proteins could cause immune reactions upon cell implantation, the goal of my project is to develop a completely synthetic material to grow human embryonic stem cells. The main focus of the project will be on finding peptides that can mimic the complex effects of the extracellular matrix proteins.
 Heather Melichar, PhD (Postdoctoral Scholar, Molecular and Cell Biology, Ellen Robey, mentor)
One goal of human embryonic stem (hES) cell research is to direct differentiation of this pluripotent cell population towards any number of cell types in vitro, for use in a variety of therapies. However, in many circumstances, the molecular mechanisms that govern these important differentiation events remain elusive. We and others have noted that several HuES cell lines vary widely, kinetically and quantitatively, in their ability to differentiate into the mesoderm lineages. Therefore, we will take advantage of the inherent dissimilarity in differentiation potential between the HuES cell lines, by comparing expression of gene-regulatory networks with the hope of defining a molecular signature in HuES cells that will distinguish their differentiation potential. This directed, genome-wide approach will improve our understanding of mesoderm-lineage development and potentially improve directed differentiation protocols.
 Joe Peltier (Predoctoral Scholar, Chemical Engineering, David Schaffer, mentor)
Adult hippocampal neural progenitor cells (AHNPCs) can generate nearly all major cell types within the mammalian brain, including neurons, astrocytes, oligodendrocytes, and endothelial cells. Understanding the mechanisms of AHNPC behavior is important for developing the strategies needed to expand them or to efficiently differentiate them into key cell types needed for neurological treatment. The aims of my work are to determine how extracellular mitogens such as fibroblast growth factor activate intracellular signaling networks mediating AHNPC proliferation, and to determine whether mechanisms that promote proliferation also promote self-renewal.
 Melanie Prasol (Predoctoral Scholar, Molecular and Cell Biology, John Ngai, mentor)
My research utilizes the murine olfactory epithelium to study principles of adult neurogenesis and neuronal stem cells. The olfactory epithelium regenerates faithfully throughout the life of the animal. Recent evidence suggests that this regenerative capability derives from one population of olfactory stem cells, the horizontal basal cells. However, the mechanisms regulating proliferation, differentiation, and maintenance are not understood. I am therefore interested in elucidating these mechanisms by identifying global changes in gene expression patterns on a genome wide scale. FACS sorting and microarray-based expression profiling will be used to analyze gene expression in horizontal basal cells during regeneration, with the goal of generating a functional genetic profile of this population of stem cells under quiescent and proliferative conditions. These studies are expected to reveal genetic networks and signaling pathways critical in adult neurogenesis.
 Haroldo Silva (Predoctoral Scholar, Bioengineering, Irina Conboy, mentor)
Human embryonic stem cells (hESCs) represent a powerful tool for early development studies, drug discovery, and regenerative medicine. However, there are two main hurdles that must be surmounted in order to realize the full potential of hESCs. The first one is to understand the molecular mechanisms regulating hESC self-renewal and pluripotency and another is to obtain functional hESC-derived cells and 3D tissues, especially in aged microenvironments. Evidence suggests that deleterious factors in the aged stem cell niche affect not only adult but also embryonic stem cells. My project's goal is therefore two-fold: (1) To investigate the effect of evolutionarily conserved signaling networks on stem cell self-renewal/differentiation and (2) to engineer a supportive matrix system composed of chemically defined factors that allow controlled 3D organogenesis even in aged or other unfavorable microenvironments.
 Melanie Worley (Predoctoral Scholar, Molecular and Cell Biology, Iswar Hariharan, mentor)
To better understand the mechanisms that control regenerative growth, the Hariharan laboratory has developed a novel system to study epimorphic regeneration using the powerful genetics of the model organism Drosophila. Larval tissues are capable of regenerating after damage through the formation of localized region of proliferation, called a blastema. As these tissues mature they lose the ability to form the blastema and proliferate in response to damage. I am conducting a large-scale genetic screen to identify factors that normally limit regenerative growth. We expect these findings to uncover more general mechanisms of regenerative growth that will apply to mammalian cells and may help reveal novel strategies for regenerative medicine.
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