Ph.D., University of California, Irvine, Cell Differentiation, 1983.
The overall objective of the Core Center for Excellence in Hematology (CCEH) is to support investigators by providing access to unique sets of reagents, resources, technical expertise and equipment that are either unavailable or cost-prohibitive at the Center. Cell Processing Core B offers the ability to obtain large quantities of specific enriched cell populations, such cells are being used to help define the molecular and functional properties that make hematopoietic stem cells unique, and to elucidate the role of other blood cell populations in engraftment, disease control, and graft-versus-host complications. In my role as Scientific Director of the Center's Clinical Cell Therapy Laboratory and the cGMP Therapeutic Manufacturing Facility, a position I have held for over 10 years, I have a very strong appreciation for quality control, quality assurance, and compliance with regulations. I also direct several research based cores, ranging from specimen repositories to multi-parameter flow cytometry to large-scale cell processing. I have been using/developing various cell sorting techniques for over 25 years, starting as a graduate student at UC Irvine through post-doctoral training at Stanford with Irv Weissman to high-speed FACS at SyStemix to the first FDA-approved CD34 selection device at CellPro. Those previous experiences, along with my current research and clinical responsibilities, have emphasized the need for teamwork, collaboration, and cooperation to help advance scientific understanding. The CCEH model continues to build on those same values by providing high quality support services to the research community. Under my leadership as Core Director, the CCEH Cell Processing core has experienced tremendous growth, supported investigators from all over the country, and contributed to a very extensive number of publications. I look forward to continuing to provide such services and be able to assist researchers in their basic science, pre-clinical, and therapeutic studies.
1999-2015 Co-Principal Investigator, NIH P30 Grant (DK56465), Core Center of Excellence in Molecular Hematology, Fred Hutchinson Cancer Research Center, Seattle, WA.
2000-2011 Director, Sub-project Core D, NIH P50 Grant (HL54881), Biology of Hematopoietic Stem Cells, Fred Hutchinson Cancer Research Center, Seattle, WA.
2000-2012 Director, Sub-project Core E, NIH PO1 Grant (CA18029), Adult Leukemia Research Center, Fred Hutchinson Cancer Research Center, Seattle, WA.
2000-2015 Director,Sub-project Core B, NIH P30 Grant (CA15704), Cancer Center Support, Fred Hutchinson Cancer Research Center, Seattle, WA.
I have a broad range of research interests, with a particular focus on the development of improved therapeutic strategies using various human stem cell populations. My long-term goals for this area are to identify better markers for the characterization of stem and progenitor cells, to improve the isolation technologies for enriching these types of cells, and to develop ex-vivo manipulation strategies that can enhance the therapeutic potential of these cells.
Another primary research area will involve studying human dendritic cell populations. I am interested in exploring the differential mobilization of distinct dendritic precursor subsets in response to specific manipulations such as cytokine treatment, the identification of unique markers to enrich those types of cells, and the ex-vivo generation of dendritic cells from precursor populations. These dendritic cells will then be manipulated to either enhance specific immune responses (e.g. anti-tumor or anti-viral activity) or dampen down inappropriate reactions (e.g. GVHD, automimmune disease, tolerance induction).
All of these research goals have a therapeutic clinical focus, and will ultimately involve the 'engineering' of patient grafts to investigate the role of specific cell populations in transplantation outcomes. This ties in directly with the Center's Cellular Therapy Laboratory and the new cGMP facility, and the role these units will play in manipulating blood and bone marrow components for the treatment of patients. It has become clear that the FDA is becoming more involved in overseeing this area of graft engineering and intends to tightly regulate this field. Thus, another goal of mine is to become very proficient in GLP, GTP and GMP regulations, both to help the Center moveforward in the development of its therapeutic strategies, and to facilitate the interactions with the FDA in this rapidly evolving area.
(Reading, Writing, Speaking)
English: (Fluent, Fluent, Fluent)
American Association for the Advancement of Science
American Society for Blood and Bone Marrow Transplantation
American Society for Blood and Bone Marrow Transplantations
American Society for Hematology
American Society of Gene Therapy
International Society for Cellular Therapy
International Society for Experimental Hematology
International Society for Hematotherapy and Graft Engineering
International Society for Stem Cell Research
Honors and Awards
1986-1988, Postdoctoral Fellowship, Leukemia Society, Stanford University
2002-2009, Associate Member, Fred Hutchinson Cancer Research Center, Clinical Research Division
2002-2009, Scientific Director, Fred Hutchinson Cancer Research Center, Therapeutic Manufacturing
2002-2009, Staff Scientist and Director, Fred Hutchinson Cancer Research Center, Cellular Therapy Laboratory
1991-1998, Biological Research Director, CellPro, Inc., Research
1990-1991, Visiting Scientist, DNAX Research Institute, Department of Immunology
1988-1990, Co-Principal Investigator, SyStemix, Palo Alto, CA
Methods and Devises for Culturing Human Hematopoietic Cells and Their Precursors, Patent Number: 5635387, 1997, Self-owned, United States of America.
Apparatus and Method for Particle Separation in a Closed Field, Patent Number: 5672481, 1997, Self-owned, United States of America.
Homogeneous Mammalian Hematopoietic Stem Cell Composition, Patent Number: 5087570, 1992, Self-owned, United States of America.
Immunotherapy of non-Hodgkin's lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified T cells.. Science translational medicine. 8(355):355ra116.. 2016.
Semi-automated closed system manufacturing of lentivirus gene-modified haematopoietic stem cells for gene therapy.. Nature communications. 7:13173.. 2016.
A Distributed Network for Intensive Longitudinal Monitoring in Metastatic Triple-Negative Breast Cancer.. Journal of the National Comprehensive Cancer Network : JNCCN. 14(1):8-17.. 2016.
Outcomes of acute leukemia patients transplanted with naive T cell-depleted stem cell grafts.. The Journal of clinical investigation. 125(7):2677-89.. 2015.
Association of fludarabine pharmacokinetic/dynamic biomarkers with donor chimerism in nonmyeloablative HCT recipients.. Cancer chemotherapy and pharmacology. 76(1):85-96.. 2015.
MIR144 and MIR451 regulate human erythropoiesis via RAB14.. British journal of haematology. 168(4):583-97.. 2015.
Identification of Differentially Methylated Markers among Cytogenetic Risk Groups of Acute Myeloid Leukemia.. Epigenetics : official journal of the DNA Methylation Society. 10(6):526-35.. 2015.
Engineering Human Peripheral Blood Stem Cell Grafts That Are Depleted of Naïve T Cells and Retain Functional Pathogen-Specific Memory T cells.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 20(5):705-16.. 2014.
Tetramer guided, cell sorter assisted production of clinical grade autologous NY-ESO-1 specific CD8(+) T cells.. Journal for immunotherapy of cancer. 2(1):36.. 2014.
Correlation of Infused CD3(+)CD8(+) Cells with Single-Donor Dominance after Double-Unit Cord Blood Transplantation.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 19(1):156-60.. 2013.
Developmental fate and cellular maturity encoded in human regulatory DNA landscapes.. Cell. 154(4):888-903.. 2013.
Systematic localization of common disease-associated variation in regulatory DNA.. Science (New York, N.Y.). 337(6099):1190-5.. 2012.
A pilot pharmacologic biomarker study of busulfan and fludarabine in hematopoietic cell transplant recipients.. Cancer chemotherapy and pharmacology. 69(1):263-272.. 2012.
Limiting the Daily Total Nucleated Cell Dose of Cryopreserved Peripheral Blood Stem Cell Products for Autologous Transplantation Improves Infusion-Related Safety with No Adverse Impact on Hematopoietic Engraftment.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 18(2):220-228.. 2012.
Early CD3 Peripheral Blood Chimerism Predicts the Long-Term Engrafting Unit Following Myeloablative Double-Cord Blood Transplantation.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 18(8):1243-9.. 2012.
MiR-27a functions as a tumor suppressor in acute leukemia by regulating 14-3-3θ.. PloS one. 7(12):e50895.. 2012.
A dilution-filtration system for removing cryoprotective agents.. Journal of biomechanical engineering. 133(2):021007.. 2011.
Identification of radiation-induced expression changes in nonimmortalized human T cells.. Radiation research. 175(2):172-84.. 2011.
Heat transfer analysis for the design and application of the passive cooling rate controlled device—Box-in-box. International Journal of Heat and Mass Transfer. 54(9-10):2136-2143.. 2011.
A random method for theoretical estimation of RBC osmotic damage in removing CPAs from cryopreserved blood with hollow fiber modules: Closed-loop blood flow mode. Journal of Membrane Science. 360(1-2):17-25.. 2010.
Developments in clinical cell therapy.. Cytotherapy. 12(3):425-8.. 2010.