The Berkeley Stem Cell Center's current CIRM Scholars, and their research interests are:
Hilliary Creely PhD (Law Scholar. Marjorie Shultz, mentor)
As a CIRM Scholar, I am studying the unique legal and policy concerns engendered by neuronal stem cell research and the potential therapeutic treatments such research will permit. I am exploring FDA regulation of extant neurological treatments to determine what new frameworks may be necessary to accommodate stem cell derived technologies and therapeutics. I am particularly interested in the rules governing the safety of both adult human test subjects and, unique to stem cell research, and the embryonic source material. I am also examining questions related to government versus private funding of neural stem cell research, approval and regulation of research projects, and the possible consequences of different regulatory strategies on biomedical research in general. For these safety and regulatory questions I am examining not only U.S. law and precedent but also perspectives from the international community, especially European Union member states. From this comparative study I hope to develop a better understanding of how the law can best keep pace with exponential scientific development in the field of stem cell research.
Joseph Dhahbi MD, PhD (Clinical Fellow, CHORI. David I. Martin, mentor)
Diseases in which the beta-globin gene is defective, such as thalassemia and sickle cell disease, affect millions of people worldwide. In higher primates, the gamma-globin gene is epigenetically silenced, and the beta-globin gene is activated at the stem cell stage of erythrocyte differentiation. The effects of beta–hemoglobinopathies could be ameliorated if this epigenetic silencing of gamma-globin could be prevented or impaired. The goal of my project is to develop a cell-based screen for small molecules that can disrupt epigenetic silencing of the gamma-globin gene. Such a molecule could also potentially alter gene expression in a wide variety of stem-cell-derived cell types.
Yick Fong PhD (Postdoctoral Scholar, Molecular and Cell Biology. Robert Tjian, mentor)
The transcriptional activators Oct4, Sox2, and Nanog are key regulators essential for self-renewal of pluripotent ES cells. Oct4 and Sox2 activate Nanog transcription by binding to the Octamer and Sox elements upstream of the putative transcription start site. I have identified a co-activator complex of approximately seven proteins that, together with Oct4 and Sox2, activates Nanog transcription. The polypeptide composition of the new cofactor will be determined by immunoprecipitation and mass spectrometry. A combination of in vitro and cell-based assays will be employed to further dissect the function of the co-activator complex.
Phung Gip (Predoctoral Scholar, Molecular and Cell Biology. Carolyn Bertozzi, mentor)
The goal of my research is to elucidate patterns of glycoprotein expression and biosynthesis toward identification of stage-specific markers during differentiation. Glycans decorate eukaryotic cell surfaces where they are poised to mediate a variety of molecular recognition events and are ideal candidates for new biomarkers. Such glycomic “fingerprints” will provide a platform for specific selection and enrichment of human embryonic stem cells of various stages of differentiation, and also provide structural information to define the functional roles of glycans in stem cell development. Human embryonic stem cells will be differentiated into various cell types using established protocols. To identify stage-specific markers associated with glycoprotein expression and biosynthesis I will: (1) Establish a global glycan “fingerprint” of defined stage-specific changes upon differentiation, (2) Perform glycoproteomics analysis using mass spectrophotometry, and (3) Characterize the genomic transcripts associated with glycoproteins.
Patrick Goodwill (Predoctoral Scholar, Bioengineering. Steven Conolly, mentor)
My research explores new ultra-sensitive ways to detect the destination and fate of stem cells following implantation. For full-animal or human studies, there is no method to track single cells in the body over a period of days to weeks, which is important to understanding stem cells in vivo. Optical imaging cannot see deeper than a cm, MRI is not very sensitive, and nuclear imaging does not enable long term tracking. I am working on a way to track cells with exquisite sensitivity by directly detecting the presence of nanometer-sized rust particles absorbed by the cell. Cells readily take up these nanoparticles, which are non-toxic and FDA approved for use in humans. This technology aims to enable long term cell tracking on live animals which we see as an important step to developing successful stem cell therapies.
Francisco Herrera PhD (Postdoctoral Scholar, Molecular and Cell Biology. Robert Tjian, mentor)
A fundamental challenge in stem cell biology is to decipher the key steps that control the differentiation of embryonic stem cells into specific cell types. In this project I am studying the transcriptional regulatory network controlled by Lmx1a, a LIM-homeobox transcription factor critical for the differentiation of embryonic stem cells into dopaminergic neurons, as well as exploring the role of alternative core promoter recognition machinery during neuronal differentiation. These studies will not only address fundamental questions in stem cell biology but also may help to develop more effective treatments for neurological diseases such as Parkinson’s disease.
Jae-Hyung Jang PhD (Postdoctoral Scholar, Chemical Engineering. David Schaffer, mentor)
Gene delivery can serve as a powerful means to regulate stem cell functions. I propose to increase the efficiency of gene delivery to embryonic stem cells using two complementary methods. Large libraries of adeno-associated viral (AAV) vector variants will be generated and used to infect stem cells, thereby amplifying variants with optimal properties for stem cell gene delivery. Substrate-mediated gene delivery; immobilization of vectors within or to a biomaterial that also serves as a substrate for ESC adhesion, will also be employed. If successful, we will explore the potential of enhanced AAV delivery to mediate homologous recombination within stem cells. We anticipate this approach can significantly increase embryonic stem cell gene targeting frequency.
Jennifer Liu (Predoctoral Scholar, Medical Anthropology. Charis Thompson, mentor)
My research is a qualitative study of practices, ethical discourses and policy-making regarding stem cell research in a transnational perspective. While many groups represent varied interests in stem cell science, this study focuses mainly on philosophers and scientists who are key players in Taiwanese policy debates. This research examines how stem cell science relates to various projects of nation-building and identity-making through the dual projects of regenerative medicine and ethical policy-making. Bioethics, as an institutionalized field, is traditionally premised on Western enlightenment ideals, however, an emergent scholarship challenges the applicability of Western ethical principles in a globalizing world and questions whether and how a global bioethics might be possible. Concomitantly, scientists pursue therapeutic and economic futures in the laboratory that have personal, national and global stakes. Based on fourteen months of ethnographic fieldwork in Taiwan, and theoretically grounded in anthropology and science studies, this research contributes to understandings of how ethical discourses, practices, and policies are made, and made to matter, in transnational movements of stem cell science and institutionalized bioethics.
Heather Melichar PhD (Postdoctoral Scholar, Molecular and Cell Biology. Ellen Robey, mentor)
One goal of human embryonic stem (HuES) 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.
Myra Mizokami MD, PhD (Clinical Fellow, CHORI. Frans Kuypers, mentor)
My research will explore the potential of modified adult T lymphocytes to facilitate engraftment of umbilical cord blood-derived stem cells into MHC-mismatched recipients. While donor T cells facilitate engraftment, they also cause graft-versus-host disease (GVHD), in which the transplanted T cells attack the recipient's tissues. To prevent GVHD, donor T cells will be treated with a psoralen compound, S-59, and UV irradiation to render them unable to divide but still allow other immunologic capabilities including cytokine release. These studies will explore the potential of treated adult T-cells to facilitate engraftment of transplanted cord blood with reduced GVHD potential in a mouse model of thalassemia.
Joseph Peltier (Predoctoral Scholar, Chemical Engineering. David Schaffer, mentor)
Adult hippocampal neural progenitor cells can generate nearly all major cell types within the mammalian brain, including neurons, astrocytes, and oligodendrocytes, which makes them promising candidates for the treatment of neurological injuries and diseases. Additionally, adult neurogenesis may play roles in learning and memory, the effects of exercise on learning, stress and depression, response to injury, and aging. Because the processes of neural progenitor proliferation and self-renewal appear to be significant regulatory points for adult neurogenesis, the purpose of my work is to determine 1) how extracellular mitogens activate intracellular signaling networks mediating neural progenitor proliferation and 2) whether mechanisms that promote proliferation also promote self-renewal. My work has already shown the importance of the Akt pathway for neural progenitor proliferation and self-renewal, and further work will investigate the signals upstream and downstream of Akt that mediate these important cellular processes.
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.
David Tolley (Law Scholar. Marjorie Shultz, mentor)
I am focusing on the unique intellectual property policies adopted by the California Institute for Regenerative Medicine (CIRM) governing state funded stem cell research. In contrast to intellectual property policies governing federally funded research, CIRM's policies require grantees who develop licensable technologies to share revenues with the State. Furthermore, exclusive licensees of technologies derived through CIRM-funded research are required to develop access plans for uninsured patients in California. I am interested in evaluating the likely effectiveness of the CIRM regulations from a policy standpoint. The regulatory scheme is clearly aimed at ensuring a "return on investment" to California taxpayers who voted for the research initiative. But will it succeed? And is the regulatory scheme set up in ways that will maximize benefits to the State? Or will the regulatory scheme create roadblocks for researchers and industry?