1. David M. Asmuth, M.D

1. David M. Asmuth, M.D. The main areas of our research focus on immune modulator therapy, and immune reconstitution in the area of HIV research. We have conducted a number of clinical studies that explore cytokine therapies (interferon alpha and IL-7), and therapeutic vaccine strategies that were designed to augment cellular immune responses in HIV infected volunteers. In this area, we have a number of ongoing research efforts to identify new ways to measure cellular immune responses to vaccination employing polychromatic flow cytometry. Additional areas of clinical research have included therapy for hepatitis B and C, especially in HIV co-infected patients. I am a clinical research member of the HIV Disease team within the UC Davis Stem Cell Program, working toward novel cell therapy trials.

2. James M. Angelastro, Ph.D. My lab focuses on controlling neural stem cell growth, including non-neoplastic and cancer stem cells through signaling pathways. The objective is to utilize these pathways to trigger stem cell growth in the brain with subsequent promotion of these cells into nerve cells that could be used to repair a damaged brain. In an alternate paradigm, we are blocking the mediators of the signaling pathways to promote prevention/eradication of brain cancer stem cells as well as the tumor. We are interacting with numerous investigators in the Stem Cell Program’s Neurodegenerative and Tumor Stem Cell Disease Teams.

3. Ramsey D. Badawi, Ph.D. My research is focused on instrumentation for molecular imaging and diagnosis in cancer, heart disease and autoimmune disease; medical image processing techniques; image- based metrics for tumor response. My group is working with Stem Cell members to develop novel radioisotope-based methods for more sensitively tracking individual stem cells in small animal models.

4. Gerhard Bauer, MD At University of California, Davis: Design, establishment and supervision of a new 6 manufacturing room GMP facility of his design for cellular products and biologics. Liaison with regulatory agencies, obtained FDA approval of the GMP facility concept, design, and QC/CA program. Conducting and supervision of all procedures performed in the GMP facility, writing of INDs for clinical trials, teaching of undergraduate, graduate and medical students within the School of Medicine and UC Davis main campus. Head of the HIV Disease Team within the Stem Cell Program at UC Davis, development of hematopoietic cells, particularly HIV resistant T cells from embryonic stem cells to re-establish an HIV- patient’s immune system. At Washington University in St. Louis: Design, establishment and supervision of a new 6 manufacturing room GMP facility of his design for cellular and gene therapy products. Conducting and supervision of all procedures performed in the GMP facility. IND-writing for gene therapy clinical trials, liaison to FDA and other regulatory agencies. At USC (Childrens Hospital of Los Angeles): Successful development of clinical stem cell gene therapy. Conducting the gene transduction part in clinical trials of hematopoietic stem cell gene therapy for HIV and ADA-deficiency. Setup and supervision of a new GMP vector transduction/production facility. Coordination and supervision of activities in the HIV-BSL 3 research laboratory. At the Johns Hopkins University: Basic research into the feasibility of stem cell gene therapy for HIV. Collaboration with the National Genome Research Institute, Clinical Gene Therapy Branch, NIH. At University of Maryland: Research in transmission of HIV from mother to child. Development of assays for the prediction of HIV-transmission from mother to child, and early detection of HIV-infection and progression in infants. Evaluation of new anti HIV drugs (including D4T and the first protease inhibitor, prior to FDA approval) in stationary cultures and a hollow-fiber system. Establishment of a new HIV BSL-3-laboratory. 5. Lars Berglund, MD Dr. Berglund’s basic research focuses on regulation of Lipoprotein and adipose tissue metabolism in HIV. He is also the Director of the Clinical Translational Science, which is designed to develop novel approaches to more effectively and rapidly move studies from the bench to the bedside, located next to the new IRC. He is working closely with the stem cell Program leaders to develop and implement safe and effective stem cell cures.

6. Dori Borjesson, Ph.D. I am a Veterinary Clinical Pathologist with training in comparative human, murine and equine hematopoiesis and pathogen-host cell interactions. My laboratory is involved in two areas which benefit from interaction and co-localization with the Stem Cell Program. We are currently sharing Dr. Nolta’s laboratory space for some of these efforts. The first is the collection, isolation and storage of stem cells derived from equine cord blood and equine bone marrow with the goal of purifying mesenchymal stem cells to address bone regeneration in horses. The second is determining mechanisms of bacterial-induced myelosuppression using human BM-derived hematopoietic stem cells and mesenchymal stem cells.

7. Douglas Boyd MD has just joined the cardiac surgical team and collaborates closely with the Nolta lab in the stem cell program, to develop novel patches for healing cardiac surgical cuts and damaged areas.

8. Simeon Boyadjiev Boyd, MD My research efforts have concentrated on congenital anomalies of the head and face, focusing on anomalies that are not caused by single gene defects. Such craniofacial defects include craniosynostosis, cleft lip and palate, facial asymmetry and ossification defects of the skull. I am interested in determining the genetic causes of these defects as well as in developing novel cures. With the stem cell program I am studying the implantation of bone- forming cells to treat craniosynostosis, facial asymmetry and ossification defects of the skull

9. Peter M. Cala, Ph.D. Our research is focused upon the fundamental, mechanistic aspects of the sodium proton exchanger, isoform type 1 (NHE1). NHE1 is responsible for cell volume and pH regulatory functions and is therefore referred to as the “housekeeping” isoform.We have also demonstrated that NHE1 plays a key role in cell damage associated with hypoxia and ischemia as well as tumor cell growth and proliferation. At present, a major thrust of the laboratory is to establish NHE1 structure-function correlates employing EPR analysis and molecular modeling of NHE1. We are working with Stem Cell Program members to determine how NHE1 modification can enhance wound repair in hypoxic regions.

10. Frederic Chedin, Ph.D. The DNA methyltransferase-Like protein, DNMT3L, is a critical factor involved in epigenetic gene regulation in both germ and stem cells. In order to first uncover the identity of DNMT3L targets, we are analyzing genome-wide DNA methylation profiles from the genome of Dnmt3L-deficient murine embryonic stem (ES) cells and comparing these profiles to the ones observed for wild-type ES cells. This research will help us determine how DNMT3L controls specific developmental processes in pluripotent cell lineages. This work is funded in part by a Training Grant from the California Institute of Regenerative Medicine. In addition, we are currently testing the hypothesis that exposure of ES cells to certain environments might alter epigenetic settings. In particular, we are interested in determining if exposure of ES cells to elevated lipid levels such as lipolysis products can perturb epigenetic patterns and cause heritable changes in gene expression. Such observation might account for the long-standing observation that offspring from obese mothers are predisposed to a higher risk of diseases throughout their lives.

11. Simon Cherry, Ph.D. Dr. Cherry’s research focuses on developing and applying in vivo imaging technologies, especially positron emission tomography (PET) and fluorescence tomography, and the combination of PET with magnetic resonance imaging and x-ray computed tomography. In recent years he has designed and constructed a microPET/microCT scanner and a MRI- compatible PET insert for multimodality imaging studies. With respect to stem cell research, he has studied different approaches for radiolabeling cells for subsequent imaging in nonhuman primates with PET, in collaboration with Dr. Tarantal’s group, and is developing new algorithms for detecting, localizing and quantifying cell distributions in vivo using a combination of PET with CT or MRI. He is working closely with the stem Cell Program to plan the immune deficient mouse imaging suites within the IRC vivarium.

12. Fitz-Roy Curry, Ph.D. For over 25 years our laboratory has investigated the mechanisms leading to acute injury in endothelial cells in individually perfused blood vessels and the modification of the permeability of the endothelial barrier in response to injury by inflammatory agents. The imaging and microperfusion methods developed in our laboratory are recognized internationally to provide a bridge between investigations of isolated endothelial cells and the permeability properties of endothelial cells in a living blood vessel. In collaboration with other Stem Cell Program members, we are testing intracellular calcium signaling in different populations of EPCs.

13. Satya Dandekar, Ph.D. Our research has been focused on mucosal immunity and infections. Currently, research projects are determining the mechanisms of the destruction of the mucosal immune defenses and immune cells in HIV infection. Future studies will focus on the repair and renewal of the mucosal immune system and immune defenses by providing stem cells. Studies will also focus on the investigation of the molecular and cellular processes of differentiation of pluripotent stem cells for replenishing damaged and impaired mucosal epithelial barrier and immune system. She is a leader of the HIV Disease team.

14. Charles DeCarli, MD We have a tremendous interest in stem cell research in general and neural progenitor cells in particular. The neuropathology component (the Neuropathology Core) of the Alzheimer’s Disease Center (ADC) will assist the various stem cell projects. The stem Cell Program will in turn help us to understand age-related neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, vascular dementia, and many others. Our initiative comes from the possibility of culturing neural progenitor cells (NPC) from post-mortem brain tissues of adults (Schwartz et al. 2003). Recently our collaborators Dr. Paul and Randi Hagerman have successfully cultured NPC from an adult patient with fragile X syndrome (Schwartz et al. 2005). This encouraging new result not only opens a source of NPC for neural differentiation and transplantation studies, but also raises the possibility of using cultured NPC as model systems tailored to individual neurodegenerative disorders. The principle that stem cell or progenitor cell cultures carrying the specific disease signatures can provide us useful tools for the study of disease mechanisms is supported by recent two articles in Nature Neuroscience using stem cells derived from SOD1 mutant mice, models of amyotrophic lateral sclerosis (Di Giorgio et al. 2007, Nagai et al. 2007). For the purpose of obtaining culturable NPC, our Center recently has enforced the “rapid autopsy” program to obtain fresh brain tissues with short post-mortem intervals that can be used for NPC recovery. This will be a useful resource for Stem Cell program researchers. To expand the horizon, Dr. Jin, who co-directs the Neuropathology Core, is also responsible for various brain banks in UCD collecting pediatric brains (in the M.I.N.D. Institute), brains with brain tumors (Neurological Surgery), and healthy normal brains. We are interested in the pathology of neural stem cells. It has been previously shown by Michael Shelanski, a well known neuropathologist in the Alzheimer field, that the A protein forming oligomers promotes the survival and neuronal differentiation from neural stem cells (Lopez-Toledano and Shelanski, 2004). The researchers in our Core have a strong interest in studying the biology of A oligomers, which are considered to play a major role in the pathogenesis of Alzheimer’s disease. Currently we are studying the effect of A oligomers on oligodendrocyte precursor cells (OPC) in culture. We also study the role of OPC in an entity called white matter hyperintensity (WMH), which is a disease of myelination associated with a subpopulation of demented individuals and has been a focus of our Center for the past decade. Close interaction with the Stem Cell Program is allowing us to broaden our investigation to include the upstream neural stem cells.

15. Wenbin Deng, Ph.D. My laboratory focuses on neural stem cell biology and regeneration in response to brain injury and disease. We are performing targeted differentiation of hESC into oligodendrocytes to use for neural repair. We will use the Stem Cell Program’s Immune Deficient Mouse core and vivarium to examine replacement of oligodendroglia in experimental neurotoxicity.

16. Ralph de Vere White, Ph.D. I focus on clinical studies to test novel cures for prostate and other cancers. My group is collaborating with the Stem Cell Program through the Cancer Stem Cell Disease team, and co-mentoring junior clinical faculty interested in this area of research. We are collaborating with the Stem Cell Program and the School of Veterinary Medicine to developing suicide gene-modified veterinary trials for metastatic osteosarcoma in the canine model, which, if successful, will translate to human trials in the new GMP facility in the UC Davis CIRM Stem Cell Institute and the Cancer Center, which are both located on the Sacramento Health Sciences campus.

17. Bruce W. Draper, Ph.D. We are studying how oocyte production in zebrafish is regulated. We have evidence that production of new oocytes is adult zebrafish is continuous and a stem cell driven process: We can readily detect mitotic germ cells as well as germ cells that express genes required for the entry into meiosis in adult ovaries. In addition, our analysis of mutations in nanos1 (nos1), the zebrafish ortholog of Drosophila nanos, gene suggest that nos1 is required to either set aside, or to maintain a population of germline stem cells in the larval ovary. We have found that while young adult wild-type females contain oocytes at all stages of development, a young adult nos1 mutant contains only late stage oocytes. This function appears evolutionarily conserved as Drosophila nanos mutant females have a nearly identical phenotype. Our current research is focused in three areas: First, we are trying to determine if germline stem cells can be identified in the zebrafish ovary using a transplantation assay. Second, we are determining when and where nos1 function for continued maintenance of oocytes production by genetic mosaic analysis. Third, nos1 encodes an RNA binding protein whose orthologs have been shown to function as negative regulators of translation. We are therefore interested in identify nos1 interacting RNAs in ovaries to gain insights into what genes are regulated by nos1 and are therefore important for oogonial stem cell maintenance. These studies are significant as oocytes production in mammals occurs only prior to birth. Thus, nanos1 may be a key evolutionarily conserved regulator of female reproductive potential.

18. Larry D. Galuppo, DVM Our research is focused on comparing four different equine tissue sources (bone marrow, adipose tissue, cord blood and placenta) for mesenchymal stem cell content, with regard to collection and preservation methods, and application for bone regeneration in horses (and canine tissues for dogs). This is a proposed 5-year investigation that will advance from in vitro and in vivo experiments isolating the optimum cell source, to developing large animal models for fracture healing and progressing to clinical trials. We are working closely with Dr. Nolta’s group within the Stem Cell Program to develop optimized stem cell isolation methods for large animals, and cell banking methods for valuable racehorses.

19. Peggy J. Farnham, Ph.D. The focus of the research in the Farnham laboratory is concerned with the changes in chromatin structure that occur upon differentiation of pluripotent stem cells along different cell lineages. Our goals are a) to determine the precise regions of active vs. silenced chromatin in a cell produced from differentiation of a cultured stem cell and b) to compare this chromatin pattern to the “normal” pattern that is in the same cell type taken from an adult. If we can demonstrate that in vitro differentiation of stem cells produces an accurate representation of the normal chromatin pattern for that cell type, this would provide evidence in support of the usefulness of in vitro differentiated cells in the treatment of human diseases. We are particularly interested in the differentiation of embryonic stem cells along the hepatocyte lineage, with the goal of determining whether the in vitro differentiated hepatocytes are a good model for hepatocyte replacement in damaged liver. This research area fits well with basic and translational research in the Stem Cell Program, and co- localization of Dr. Farnham’s students with the Liver Disease Team in the new Stem Cell Institute will move the research forward even more quickly.

20. M Eric Gershwin. MD I oversee a program focused on dissecting the mechanisms of autoimmunity in primary biliary cirrhosis. This includes a program involving seven postdoctoral fellows, two graduate students and a technician. This program began in 1986 while I was on sabbatical at the Hall Institute in Melbourne, Australia and cloned PDC-E2, the major mitochondrial autoantigen of PBC. Clinical cellular therapy trials to reduce or eliminate the severity of autoimmune diseases will be done in the new GMP facility in the Stem Cell Institute. Drs. Nolta and Bauer are co-investigators on the pending clinical trial to perform stem cell-mediated therapy for Biliary Cirrhosis.

21. Ralph Green, MD, PhD My group works on better understanding the effects of vitamin B12 deficiency on the vasculature and the blood forming system. We are interested in differential effects on hematopoietic and endothelial progenitor cells and are studying epigenetic modifications.

22. Hagerman, Randi Jenssen MD Dr. Hagerman has more than 20 years of experience in the field of neurodevelopmental disorders and fragile X syndrome - the most common inherited cause of mental retardation. Her research focuses on the correlation between an individual's molecular genotype, or genetic make-up, and their physical and behavioral characteristics. She also has a strong clinical and research interest in autism and has conducted research examining the association between autism and fragile X syndrome. She has recently successfully cultured NPC from an adult patient with fragile X syndrome, which raises the possibility of using cultured NPC as model systems tailored to individual neurodegenerative disorders. M.I.N.D. Institute faculty have developed the “rapid autopsy” program to obtain fresh brain specimens for NPC recovery. With the Nolta lab and UCSD she is developing iPSC from patients with FXTAS.

23. Kei Hayashi, Ph.D., DVM I study joint regeneration and joint repair, and perform research in cellular changes in ruptured canine ligaments and ligament pathophysiology. I am working with the Stem Cell Program’s Bone and Cartilage Disease Team. Large animal models of joint degeneration and spontaneous injury, seen in our veterinary clinics, can be tested in veterinary trials, and if randomized phase I/II trials can be done in sufficient numbers to achieve significance, resulting data can be used to support IND applications for human clinical trials.

24. Thomas R. Huser, Ph.D. Ultra-sensitive laser microscopy and spectroscopy of the nanosystems biology of individual cells and organisms. Projects include the development of intracellular nanosensors based on surface-enhanced Raman spectroscopy for the cellular and molecular imaging of chemical traffic in individual cells; Raman and coherent anti-Stokes Raman spectroscopy (CARS) of individual cells, micro-organisms, and lipoproteins with the purpose of characterizing biochemical markers (phenotypes) and their changes with cell development and in response to external events; the study of DNA-protein and protein-protein interactions by single molecule fluorescence spectroscopy; multi-photon induced fluorescence and biomaterials modification; and the development of an ultra-sensitive immunoassay for the detection of proteins, cancer-markers (mRNA), toxins, and viruses based on single molecule fluorescence detection in a microfluidic device. Working with the Stem Cell Program to develop novel methods to identify and viably sort many types of stem cells based only on their intrinsic qualities, without labeling.

25. Dallas Hyde, Ph.D. My research is focused on airways epithelial and inflammatory/immune cell interaction. Interaction of these cells maintains homeostasis (ability to combat infectious disease, removal and/or repair of injured cells) in the lung. My laboratory is interested in asthma, pulmonary fibrosis and emphysema as models for investigation. We are interested in stem cells to regenerate damaged lung tissue in non-human primates.

26. Roslyn Rivkah Isseroff, MD Dr. Isseroff has research interests that include keratinocyte differentiation, migration, and wound healing; signal transduction; bioengineered skin replacement; and toxicology of the skin. Collaborative research projects with the Skin Disease Team in immune deficient mice focus on stem cell migration and repair of non-healing ulcers. Studies on galvanotaxis (mechanism by which cells migrate in response to an applied electric field) and bioengineered skin grafts are also under study. She runs a certified tissue bioengineering laboratory that will be relocated to the new Institute for Regenerative Cures in 2010. 27. Jinoh Kim Ph.D. Dr. Kim is a cell biologist with expertise in intracellular protein trafficking. He is studying genetic disorders and bacterial infectious disease which cause defective protein transport from the endoplasmic reticulum (ER). Using biochemical and cell biological approaches, Dr. Kim has focused on biogenesis of gamma–secretase, an important enzyme complex responsible for generation of toxic amyloid peptide. He discovered that some familial Alzheimer’s disease (FAD)-linked presenilin 1 (PS1) mutant proteins cause aberrant export of gamma–secretase from the ER. Dr. Kim’s laboratory is currently pursuing proteins recycling ER and Golgi compartments which control development and maintenance of brain and stem cells.

28. Paul Knoepfler, Ph.D. My research program is focused on epigenetic programming of neural, hematopoietic, and embryonic stem cells with a particular interest in the regulation of self-renewal and pluripotency by the Myc family of proto-oncogenes and histone modifying enzymes. We are also interested in how stem cell programming controls normal and neoplastic tissue growth with the goal of devising regenerative medicine therapies that are both safe and effective.

29. Eric A. Kurzrock, MD The pediatric urology/stem cell laboratory is focused on the investigation of urothelial stem cells and differentiation. We seek to identify, characterize and enrich for adult (lineage specific) and embryonic-derived urothelial stem cells. We are studying animal models as well as human embryonic cells. Our group is focusing on reconstruction of urinary bladder using adult and hESC with tissue engineering techniques. We study the process of differentiation of hESC into definitive endoderm particularly urothelium by in-vitro and in-vivo conditions. We are collaborating with both basic and translational researchers in the Stem Cell Program and co-localization of our laboratories will enhance the speed and efficiency with which the studies can progress.

30. Kit Lam, MD, Ph.D. Our research encompasses the development and applications of combinatorial chemistry to basic research and drug development. On-going projects in his laboratory include the development of novel encoding techniques and screening methods for one-bead one- compound “OBOC” combinatorial libraries, development of cancer cell surface targeting agents for cancer therapy and in vivo imaging, identification of substrates and development of inhibitors for protein kinases and proteases, development of novel cell adhesion ligands and chemically defiend synthetic gel matrix for 3-D cell culture, applications of OBOC combinatorial library methods and chemical microarrays for cancer proteomics and enzyme profiling, development of novel glyco-markers for cancer diagnosis, development of imaging and therapeutic agents for Alzheimer’s disease, and development of antiviral agents. We are collaborating with multiple investigators throughout the Stem Cell Program.

31. Nancy E. Lane, MD My laboratory and clinical research groups focus on osteoarthritis and osteoporosis, the most common degenerative diseases of the elderly. The research group has participated in an NIH funded multicenter study to determine if the sugars glucosamine and chondroitin alter the progression of knee OA. My laboratory investigates the activation of osteoclast cells that breakdown bone, and my clinical studies are focused on interventions to reverse glucocorticoid-induced osteoporosis (an unfortunate complication of long-term glucocorticoid use in rheumatic disease patients). My group is now evaluating in the laboratory how glucocorticoids alter bone cell lifespan and bone strength (by nanoidentation methods), and in the clinic studies are underway to determine how to maintain the new bone formed by PTH in patients on glucocorticoids. Our research team is developing a stem cell research program targeting potential therapy for osteoporosis. This program will encompass basic to clinical studies and will include the fundamental biology of stem cell development of treatments incorporating in vivo models. As developments warrant we will test outcomes of the use of candidate therapeutics or procedures through animal modeling in the Stem Cell Institute.

32. J. Kent Leach, Ph.D. Our studies are focused on discovering the appropriate combinations of stimuli to promote the formation or regeneration of functional tissues. We utilize commercially available and novel biomaterials, soluble inductive factors, and various stem and progenitor cell populations to pursue our efforts in tissue engineering. We are actively engaged with investigators who are focused on the biological events ongoing in stem and progenitor cells, and we seek to harness this knowledge for use in regenerative medicine.

33. Fu-Tong Liu, MD, Ph.D. Our research is focused on the studies of a family of animal lectins, galectins, which are beta-galactoside-binding proteins. These proteins have been implicated in a variety of physiological and pathological processes. We are focusing on the role of some of the members in the inflammatory response and host innate immunity. We are also studying their roles in tissue regeneration, specifically skin wound repair, through their functions in regulation of cell growth, apoptosis, and migration, as well as their contributions to the inflammatory response. Future research includes i) the roles of various galectins in the proliferation, differentiation, and biological functions of stem cells; ii) the effect of inflammation on tissue regeneration; and iii) interactions between stem cells and inflammatory cells.

34. K.C. Kent Lloyd, Ph.D. Since coming to UC Davis in 1996, I have maintained an active, competitive, extramurally- funded, and growing research program which is based on the development and study of animal models of human and animal disease, development, and behavior. Today, my research has become more integrative by employing cellular and molecular approaches, thus necessitating the use of smaller and specialized animal models (wildtype and genetically-altered mice). These latter studies have required me to become proficient in transgenesis and comparative functional genomics. As a result, the major focus of my primary and collaborative research efforts over the last 3 years has been in mutagenesis, embryonic stem cell biology, and germplasm manipulation, such as preservation, nuclear reprogramming ("cloning"), in vitro fertilization, and intracytoplasmic sperm injection. A few highlights of my research activity over the last 3 years are worth mentioning. For example, my laboratory successfully derived embryonic stem (ES) cells from C57BL/6 mouse embryos that remain viable and pluripotent after multiple passages in culture, thus making them amenable for high-throughput mutagenesis. We have also demonstrated that not only are mitogenic growth factors, such as EGF and TGF , essential for normal pre-implantation embryo development, but that nuclear reprogramming and clonally-derived mouse embryos can be enhanced by supplementation of these growth factors. We have also developed techniques for controlled dessication of sperm cells that can be stored indefinitely at low temperature and upon rehydration be viable for assisted fertilization, such as by intracytoplasmic sperm injection.

35. Reginald Low, M.D. Development of percutaneous aortic valve replacement and percutaneous mitral repair. Developing Stem Cell Trials to reverse cardiac ischemia in collaboration with the Stem Cell Program and a corporate sponsor. Doug Boyd MD and Ming Si MD have just joined the cardiac surgical team and collaborate closely with the Nolta lab in the stem cell program.

36. Laura Marcu Ph.D. L. Marcu’s research is in the general area of biophotonics and includes studies of molecular changes in tissues by means of optical spectroscopy and imaging, and the application of the knowledge gained to engineer biophotonic devices for early diagnostic, treatment and prevention of diseases. Her work is related to bioengineering for the solution of societal problems in disease and health: atherosclerotic cardiovascular disease and cancer which are the most critical of human diseases. The optical techniques developed in her lab have significant potential to contribute to stem cell research by providing non-intrusive, non- destructive methods for characterization of bioengineered tissue. For example, L. Marcu’s group applied for the first time an optical spectroscopy technique to characterization of bioengineered tissue.

37. Dennis L. Matthews, Ph.D. Dr. Matthews is the CBST Director, holds a joint Appointment at UC Davis College of Engineering, School of Medicine and is the Program Leader of the Medical Technology Program at Lawrence Livermore National Laboratory. He is also an Associate Director of the UC Davis Integrated Cancer Program. He is responsible for the development of industrial and medical applications of Lawrence Livermore National Lab Technology, especially for the prevention, screening, diagnosis and treatment of diseases such as diabetes, stroke, brain trauma, chronic pain and cardiovascular disease. Current projects and those already successfully transferred to industry include: an opto-acoustic recanalization device for treating ischemic stroke; a miniature x-ray source which is mounted on a microcatheter and used to treat coronary artery restenosis; micropower impulse radar for numerous medical diagnostics including differentiating hemorrhagic vs. ischemic stroke; an implantable, continuous glucose monitor and ultra-short-pulse laser microsurgery devices.

38. Frederick J. Meyers MD Dr. Meyers directs the CIRM-funded stem cell training grant at UC Davis. He is ideally suited to lead this proposal because of the breadth of his cancer research experience (basic and translational research including molecular biology, clinical trials, health services research). In addition Dr. Meyers directs the UC Davis Clinical and Translational Science Center (CTSC) Research Training and Education Program and is the PI of the K30/Mentored Clinical Research Training Program within the CTSC. In addition to his training grant funding he is completing an NIH grant on ethics and palliative care in cancer investigational trials, bringing to the stem cell program another dimension. Dr. Meyers also serves as a national leader in academic Internal Medicine and has led the discussion on residency training, many concepts and issues that are now being utilized in the stem cell program including competency based training and professionalism.

39. Wiliam Murphy Ph.D. Bill is a new recruit to the stem cell program who is an internationally well- respected expert in natural killer cell biology and immunotherapy. His lab is collaborating closely with the Nolta lab and throughout the stem cell program to use cellular therapies to kill cancer stem cells. Drs. Murphy and Nolta have a jointly funded CIRM project to study the immunology of embryonic stem cell transplantation. 40. Liping Nie, Ph.D. Our long-term goals are to stimulate hair cell (HC) regeneration in human inner ears, in a controlled fashion, and to enable the functional innervation of the regenerated HCs by spiral ganglion neurons (SGNs). HCs are terminally differentiated cells. The terminal mitosis of HC progenitors completes before birth. Once HCs are lost due to noise, ototoxic drugs or aging, there is no effective way to stimulate HC regeneration. However, recent studies from our group and others have demonstrated very encouraging results: new HCs can be successfully induced in the cochlea after birth suggesting that mammalian inner ears maintain the capacity to produce limited new HCs even after birth. Moreover we have identified human somatic and embryonic stem cells (hESCs) that have the competence to differentiate into HC-like units and neurons. Currently, we are conducting experiments to identify the candidate proteins and their mechanisms of interaction that are required to induce HC and SGN differentiation from hESCs. The project will determine the hESC-types that have the competence to transform into HCs. We will assess whether a hair cell assembles its entire transduction apparatus and ionic conductances simultaneously, or whether the assembly of the final apparatus entails multiple steps. Moreover, these studies should reveal how HCs and SGNs coordinate and regulate the mechano-electrical apparatus, information that might be exploited to induce HC and SGN regeneration after damage. Of particular clinical importance to auditory and vestibular science is the possibility that a rational design of a cocktail of factors may be assembled to induce HC and SGN differentiation in matured inner ear. Moreover, these studies transcend HC-specific functions. Since the mechanisms used by HCs may be expressed in different forms by other signal transduction systems, these studies may provide novel insights into hESC differentiation and signaling.

41. Jan A. Nolta, Ph.D. My lab studies human embryonic vs. adult stem cells to improve their recruitment to areas of tissue damage in immune deficient mice. Our research is focused on developing improved stem cell therapies for treating patients with neurodegenerative disorders including Huntington’s disease, liver disease, cardiac infarction, peripheral vascular disease, and other disorders. Our main area of interest is to determine how stem cells are attracted from the bloodstream into areas of ischemic damage, and to make this recruitment more robust. My group focuses on “bench to the bedside” research, conducted at the level of good laboratory practice.

I am the Director of the Stem Cell Program at UC Davis School of Medicine, and I direct the new Institute for Regenerative Cures. The UC Davis stem cell program has over 145 faculty members collaborating to work toward stem cell-related cures for a spectrum of diseases and injuries. The current research in our own laboratory is focused on “bench to the bedside” translational studies, and I have been involved in numerous clinical trials of gene and cell therapy. In 1994 I developed my passion for cellular therapy by helping to perform the first cord blood stem cell gene therapy trials for newborns with “bubble baby disease”, with my Ph.D. mentor Donald Kohn at the University of Southern California. A scientist with more than 20 years’ experience with human stem cells, I have published over 100 manuscripts in the stem cell field and have authored 15 book chapters. I have served on over 60 review panels for the National Institutes of Health, am Associate Editor for the Journal “Stem Cells” and was editor of the Book "Genetic Engineering of Mesenchymal Stem Cells". As Director of the Stem Cell Program at UC Davis, I am involved in animal modeling for the majority of our Disease Teams and am helping basic and translational investigators move their therapies into clinical trials, to be done in our new CIRM-funded GMP facility. 42. Tina L. Palmieri, MD Stem cell research has enormous potential in my area of research interest: burn injury. Current therapeutic modalities for burn injury involve removal of the burn and placement of skin grafts obtained from unburned areas on the patient. Although advances have been made in the treatment of burn wounds, such as cultured epidermal autograft and “artificial skin”, neither provides for adequate wound coverage. Engineering stem cells to regenerate skin and other injured organs would revolutionize burn care. We have a basic science laboratory which investigates the role of glucocorticoid receptors and human endogenous retroviruses in burns. In addition, our translational research program, which is investigating the hypothalamic-pituitary-adrenal response (including glucocorticoid receptors) and the role of endogenous retroviruses in blood transfusion, can translate the advances generated by stem cell research into the clinical realm. We will continue working closely with the Stem Cell Program to make this a reality.

43. Chong-Xian Pan, MD PhD The long-term goal of the proposed research project is to develop ligands specifically targeting cancer stem cells using combinatorial chemistry approaches. In most malignancies, a small group of cells named cancer stem cells (CSCs) can regenerate themselves and differentiate into progeny cancer cells. CSCs are relatively resistant to current treatments that target differentiated cancer cells. CSCs and normal stem cells have different cell surface molecules. It has been shown in vitro that targeting cell surface molecules specifically expressed on CSCs can kill CSCs while sparing their normal counterpart cells. In the project, I will use the UC Davis stem cell facilities to isolate CSCs, then take combinatorial chemistry approaches to develop ligands that specifically target CSCs while sparing normal differentiated and stem cells. I will also identify the cell surface target molecules that are specifically expressed on CSCs and elucidate their functions. We are working closely with Stem Cell Program members on these projects, will have a designated room in the new facility, and will translate promising research into clinical trials through the CTSC and stem cell program.

44. Susanna S Park, MD PhD We are performing preclinical studies to study the effect of intravitreally administered bone marrow stem cells in treating retinal vascular disease. We have just completed FDA- mandated 6 month biosafety testing to start a pilot clinical trial investigating the use of autologous bone marrow stem cells administered intravitreally in treating patients with acute vision loss from retinal vascular occlusion. These studies are being conducted through the immunodeficient mouse core of the stem Cell Program, GP studies in Dr. Nolta’s lab, and scale-up is done by the GMP facility staff.

45. Kent Pinkerton, Ph.D. My research focuses on the respiratory system and health. General themes addressed: (1) mechanisms of particulate toxicity, (2) effects of oxidant gases on lung injury and repair, (3) effects of environmental pollutants on lung development and immune responses during perinatal life, (4) mechanisms of tobacco smoke-induced lung inflammation and (5) diet, chemotherapeutic agents and inhibitors of inflammation to reduce tumor risk in an animal model of tobacco-induced lung disease. We are a part of the Lung Disease Team and are interested in stem cell therapies for lung damage and acute inflammation.

46. David Pleasure MD My focus is on development and regeneration of the central nervous system, specifically on the role of neural stem cells in the generation of oligodendroglia. I am an associate director of the UC Davis Stem Cell Program and we are interacting on many levels.

47. Richard Pollard MD My interest in stem cell research derives from my long standing interest in viral infections particularly in patients infected with HIV. There have been historical attempts to utilize various cell populations to influence the course of patients with advanced HIV infections which have had moderate success at best. With current methods of stem cell preparation and expansion the possibility of utilizing stem cells in the future seems much more likely. Recent efforts have focused on techniques of transferring small RNA molecules or other structures which would make cells unable to support HIV infection. It seems likely that these techniques could be utilized in autologous cells which could be ex vivo exposed to these molecules, the cells expanded and then returned to the host. As such, they would have a selective advantage over the individual’s own cells which remain susceptible to HIV infection. The expanded cells will repopulate the patient’s immune system. Our GMP facility Director, Dr. Bauer, has conducted many similar clinical gene therapy trials. Improved and hESC-based techniques could focus on patients who have later stage HIV infection or in patients who have had virological responses to antiretroviral therapy but, who have not responded with return of their immune system. This group of patients makes up 10-15% of patients treated with antiretrovirals and could benefit greatly from these efforts. I am a part of the HIV Disease Team in the stem cell program at UC Davis Medical Center where collaborative scale-up studies are ongoing.

48. Suzanne Pontow, Ph.D. For the past decade, my research focus has been the cellular determinants of viral infections, using lentiviral and pox viruses as model infectious agents. A common theme in the life cycles of these diverse viral types is the opportunistic manipulation of intracellular factors and signal pathways, through ligation of cell-surface receptors, to promote or facilitate productive infection. My interests have recently turned to stem cells, and the ways in which scientists may be able to influence their behavior to promote tissue regeneration or repair. Presently, my studies are centered on the chemokine receptor and HIV co-receptor, CXCR4, as it is utilized by human stem cells to migrate to and repopulate injured or diseased tissue. I have joined Dr. Nolta’s group at UC Davis Medical Center to study the function and signaling activities of CXCR4 in human embryonic stem cell lines, for comparison with adult hematopoietic or mesenchymal stem cells. Through these studies, we hope to define critical factors essential to the processes of stem cell homing and tissue retention in transplanted mouse models. In the future, these critical factors will be experimentally manipulated to optimize stem cell migration and implantation, with the goal of producing clinically usable reagents and protocols for regenerative medicine and stem cell- based therapies. I am also very much involved in directing students in the CIRM-funded Bridges training program.

49. Hari Reddi Ph.D. Dr. Reddi is an endowed chair and is the Director of the Center for Tissue Regeneration and Repair at UC Davis. He is one of the pioneers in identifying BMPs and their application in cartilage and bone tissue engineering. He has been focused on articular cartilage tissue engineering using mesenchymal stem cells during the last ten years.

50. Alexander Revzin Ph.D. I am a part of the liver disease team and I study the effects of micropatterning ECM molecules and growth factors on the development of hepatocytes from hESC.

51. Carol M. Richman, M.D. As Medical Director of the Clinical Progenitor Lab and the new UC Davis Good Manufacturing Practice facility, I will assist investigators in planning and executing stem cell therapy in patients. The daily activities of our Clinical Lab and the Clinical Stem Cell Transplant Program focus on harvesting, freezing, thawing and reinfusing cells to restore hematopoiesis. The progenitor lab will be moved into the GMP facility upon its completion, so that all stem cell manipulations can be done ensuring Good Tissue Practice. We have experience with umbilical cord blood transplants, harvesting marrow cells for orthopedic regeneration, and standard clinical stem cell transplant therapy for malignancy. This expertise will be needed to translate findings of laboratory research into the treatment of patients with malignancies and other disorders that can benefit from the regenerative/modulating properties of stem cells. We have already initiated collaborations and scale-up for clinical cellular therapy trials with investigators in orthopedics, ophthalmology, gastroenterology, and rheumatology in addition to the Stem Cell Program. All cell manipulations for these cellular therapy trials will be performed in the GMP facility of the new Stem Cell Institute.

52. Michael A. Rogawski, MD, Ph.D. Evaluation of stem cell-based therapeutic approaches for epilepsy in diverse animal epilepsy models. Controlled delivery of stem cells to the central nervous system in experimental models of neurological disease using convection-enhanced delivery. Developing novel models to apply this technology to human stem cells in immune deficient mice, which will be done in the vivarium of the new IRC Facility. Our novel therapeutics will be manufactured in the UC Davis GMP facility.

53. Pablo Ross, Ph.D. Pablo is a new recruit to UC Davis who is a well known expert in induced pluripotent stem cell biology. He is collaborating already with the HIV team and others throughout the stem cell program.

54. John C. Rutledge, MD We have a Cell and Molecular Imaging Grant from the NIH to determine the interactions between triglyceride-rich lipoproteins (TGRL) with lipid rafts present on endothelial progenitor cells (EPC), and to determine the effect of TGRL on endothelial progenitor cell function. Lipid rafts on EPCs and monocytes will be fluorescently labeled, and Individual cells will be isolated using laser tweezers and analyzed for changes within the rafts by fluorescent microscopy and Raman spectroscopy. The Raman will be done in collaboration with the Biophotonics group. Other researchers in the Stem Cell Program are also working on lipid raft biology and this technology will be applicable to different stem cell types such as hESC.

55. Noriko Satake, MD I am a pediatric BMT clinician who is working in the Nolta lab to study leukemic stem cell growth in immune deficient mice, and to develop, with Drs Lam, Pan, and Nolta, novel methods to kill leukemic stem cells in the most aggressive pediatric diseases that affect my patients. I am funded by the Hyundai Foundation.

56. Scott Simon Ph.D. We are interested in the use of human embryonic stem cells (hESC) as a basis for differentiation into endothelial progenitor cells. Repopulation of blood vessels requires a detailed knowledge of the response of highly proliferative endothelium to inflammatory mediators. In the Simon laboratory, we are investigating the relation between inflammation and stem cell differentiation and endothelial phenotype. Our Areas of expertise are Inflammation, Atherosclerosis, Vascular and Leukocyte Adhesion Molecules, Mechano- biology and Signal Transduction. Technologies developed are based on fluorescence microscopy, flow cytometry, microfluidics to image leukocyte function on vascular mimetic models of vascular diseases.

57. Jeffrey Allen Southard, MD I am performing clinical trials in the Vascular Center and am collaborating with the Stem Cell Program to develop novel methods to deliver Human Stem Cells into regions of ischemic tissue damage in the cardiovascular trials. We will be using catheter technology patented at UC Davis. We are currently accruing patients to a cardiovascular trial of stem cell therapy.

58. Julie Sutcliffe, Ph.D. Dr. Sutcliffe’s research involves the design, synthesis and in vivo evaluation of targeted molecular imaging agents with a focus on PET. Her group has developed rapid radiolabeling technologies using both solid-phase and solution-phase chemistries to incorporate the short half-life PET radionuclide 18F into peptides. Peptide based radiopharmaceuticals are gaining extensive attention as targeted molecular imaging agents. It is therefore important that technologies are developed that allow these agents to be synthesized rapidly and screened both in vitro and in vivo to assess their efficacy. Her group applies radiolabeled peptides to target cell surface receptors in vivo using small animal imaging. Major cell surface receptors of interest include the integrin receptors avb3 and avb6. Integrins are cell surface glycoproteins involved in cell-cell and cell- extracellular matrix interactions. Their over expression has been associated with many diseases including cancer. In particular avb6 is expressed at low or undetectable levels on normal tissue and is upregulated on many cancers including oral squamous cell carcinoma, breast cancer, pancreatic cancer and has recently been identified as a marker of prognosis in colon and lung cancer. In vivo imaging of this receptor could therefore have a significant impact on patient diagnosis, care and management. Dr Sutcliffe’s group use two approaches to develop targeted molecular imaging agents to image cell surface receptors A “rational approach” based on known binding structures and a “random approach” using the one-bead-one-compound molecular library methodology. It is anticipated that these methodologies will have applications for stem cell trafficking in vivo using PET. These technologies are also amenable to other imaging modalities including optical and MRI.

59. Colleen Sweeney, Ph.D. My laboratory focuses on the contribution of receptor tyrosine kinases to breast tumor initiation and progression using a variety of cell culture and animal models. We are also interested in mechanisms of therapeutic resistance to targeted agents. We are affiliated with the Stem Cell Program through the Cancer Stem Cell group and will share cores in the new facility.

60. Fern Tablin, Ph.D. My laboratory has a long history both in hematopoiesis as well as development of methods to improve storage of both platelets and eukaryotic cells in the dry state (please see relevant patents). In addition, my laboratory has expertise in platelet production and platelet physiology. I am working with the Stem Cell Program and the Blood Disorders Team to improve cryopreservation techniques for hematopoietic stem cells and their derivatives.

61. Alice Tarantal Ph.D. Dr. Tarantal is Professor in the Departments of Pediatrics and Cell Biology and Human Anatomy in the School of Medicine, and Staff Scientist and Reproductive Sciences Unit Leader at the Primate Center. The activities in Dr. Tarantal's research program covers the following areas of nonhuman primate translational research: (1) stem cells/cell-based therapies, (2) gene therapy, (3) monkey models of human disease, (4) fetal:maternal microchimerism, and (5) the use of in vivo imaging applications. Dr. Tarantal has NIH- and CIRM-supported projects that focus on human hematopoietic, mesenchymal, endothelial, and embryonic stem cells (ESC). She compares and contrasts adult and hESC populations for tissue regeneration and repair and transplant purposes. Other goals include identifying methods to effectively differentiate hESC towards defined renal, endothelial, and hematopoietic lineages and in sufficient quantity for tranplant purposes, and developing in vivo imaging techniques using microPET and optical imaging combined with ultrasound for tracking and monitoring cells post-transplant. Studies on maternal:fetal microchimerism focus on the source and function(s) of the cells in the maternal compartment, and the role of these cells in health and disease. Dr. Tarantal has a long-standing commitment to providing research opportunities to investigators, and fostering multidisciplinary, translational collaborations. Through two NIH-supported Centers, many services and opportunities for translational research specific to stem/progenitor cells and gene therapy are provided to the greater research community. The Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases conducts research on crucial questions in gene therapy in nonhuman primates (all age groups), and provides extensive outreach and services to NHLBI-funded investigators. Similarly, the Center of Excellence in Translational Human Stem Cell Research consists of research projects that encompass central themes of cell expansion and reconstitution, transplantation and cell fate, pediatric nonhuman primate models, and in vivo imaging. The Pilot and Feasibility Program also supports studies with investigators nationally.

62. David G. Telander, MD Our goal is to speed the development of stem cell therapies for the many blinding diseases of the retina, such as age-related macular degeneration (AMD) and retinitis pigmentosa. We will conduct our studies in ways that will facilitate currently planned and future human clinical trials. Our studies will use human stem cells (adult bone marrow and embryonic) to help clarify their consistent efficacy, reliability and safety. We will use methods that meet the standards mandated by the Food and Drug Administration for use in human therapy. This will give us essential safety data that is needed for cellular therapy trials. In addition, our studies will directly compare adult vs. embryonic stem cells, to determine advantages and disadvantages of each. Two specific issues in the successful use of stem cells in treatment for debilitating retinal diseases will be addressed: 1) successful migration of the stem cells and 2) long-term survival of integrated donor cells. The first hurdle is to gain a better understanding of both adult and embryonic stem cell migration and to determine how administration to the eye alters their homing. This information will be critical in the progress toward clinical therapies. Collaborative studies are ongoing at Tupper Hall and in Temporary space at Shriners Hospital, and future research will be done in the Stem Cell Institute, when the retinal group has a common shared area there. A clinical trial of retinal repair/revascularization is pending additional safety data, as requested by the FDA, and the validation experiments are currently being conducted in the Stem Cell Program’s Immune deficient Mouse Core. 63. Martin Vidal, Ph.D., DVM The emphasis of my research thus far has been the comparison and characterization of cell frequency, growth and the multipotential differentiation capacity (adipogenic, osteogenic and chondrogenic) of equine mesenchymal stromal cells derived from bone marrow and adipose tissue. This work entailed histochemical analysis of mesenchymal cell differentiation as well compositional and mRNA level quantification of pellet cultures grown under chondrogenic differentiation conditions. Furthermore we have investigated cell culture and tissue growth characteristics of marrow derived stem cells in low shear microgravity culture systems with the aim to apply these insights toward regenerative tissue repair in equine tendon/ligaments and bone. I am working in the UC Davis Equine group, which is closely collaborating with the Stem Cell Program. My research will be done primarily in our new, state of the art Veterinary Medicine facilities but will use the cores in the new Stem Cell Institute and will share space there with the bone group, to test applications where equine cells can initially be tested in immune deficient mice, before proceeding to horses and then humans.

64. Jian Wu, MD, PhD As a co-investigator of Dr. Mark A. Zern’s stem cell research team, I have engaged in all research activities of mouse, primate and human embryonic stem cells, as well as CD34+ bone marrow stem cells. My personal interest in stem cell biology will mainly focus on hepatic oval cells in regenerative liver, such as remaining liver after partial hepatectomy, small size graft in recipients of living donor liver transplantation, etc. In addition, for moving my current research project: “Antioxidative gene therapy for liver transplantation” to a clinical trial stage, we will use the Stem Cell Program’s Vector Core and the GMP facility for generating gene therapy constructs and reagents at the necessary GMP standard.

65. Reen Wu, Ph.D. Our research programs relevant to the Stem Cell Program are related to the use of embryonic stem cells (ESC) for lung regenerative medicine. We have defined the culture conditions that are required to direct mouse and human ESC toward the differentiation of lung and airway epithelial cell phenotypes. We will sort out lung-specific progenitor cell types derived from ESC cultures and repopulate them in transplanted tracheal grafts in rats and immune deficient mice. Using this approach, we will address if cystic fibrosis epithelium or chemically damaged airway epithelium can be regenerated by these selected ESC-derived lung progenitor cells.

66. Mark Zern, Ph.D. Because there is still considerable morbidity and mortality associated with the process of transplantation, and because more than a thousand people die each year while on the liver transplantation list, it is evident that improved and safer liver transplantation would be valuable, as would approaches that provide for an increased number of transplantations in a timely manner. A technology that might address these issues is the development of a proliferative human hepatocyte-like line that can be employed in liver cell transplantation or in a bioartificial assist device. Developing such a cell line from human embryonic stem cells (hESC), human fetal hepatocytes (FH) that have been immortalized with telomerase reconstitution (hTERT), or from Omnicytes (an adherent population of human CD34+ cells) would provide a valuable tool for pharmacology and toxicology studies, as well as for use in cell-based therapeutics. Developing methodologies to non-invasively monitor the fate of these immortalized cells on a longitudinal basis when they are transplanted in vivo will provide invaluable information about their potential therapeutic use, as will employing them in cell transplantation studies in nonhuman primates. If stem cell research is ever to meet the very high expectations placed on it to develop therapeutic applications, hard questions should be asked and answered in an objective manner. We will attempt to critically compare and contrast these three very different stem cell populations to determine which will be the most effective hepatocyte-like cells in in vitro and in vivo studies.

67. Min Zhao, Ph.D. Research in my laboratory focuses on spatially regulated cell and tissue growth in wound healing and regeneration. Proliferation, migration and differentiation of repairing cells in a spatially controlled manner are critical to regenerate proper tissues. We have been working on signals that give cells a sense of direction. In the recent years, my laboratory is specifically interested in studying naturally occurring electric signals at wounds and regenerative sites in our bodies in guiding cells to migrate to heal wounds and regenerate. Our discovery that the physiological electric fields play a predominant role in guiding epithelial wound healing was published in Nature and other journals and has been commented in New England Journal of Medicine.

One of our specific interests is to control stem cells to migrate and differentiate in a spatially organized manner. We have started our work on intrinsic control of stem cell migration and the effects of differentiation. We are also studying using electric signals to guide migration and differentiation of stem cell and progenitor cells. Those are integral to the stem cell research at UC Davis. The facilities will be a great base for our research. I am collaborating with the Skin Disease Team in the Stem Cell Program and the practical outcome fo our group research will be to more rapidly heal burns and skin ulcers