Principal Investigators

Quicklinks Gene, Immune & Stem Cell Therapy Developmental Biology Cardiovascular / Tissue Engineering Cancer

Gene, Immune and Stem Cell Therapy (GISCT)

Gay Crooks, MD,  is the director of the Childrens Hospital Los Angeles Stem Cell Project.  Dr. Crooks has been studying human stem cells in the bone marrow and umbilical cord blood for 14 years. In 2004, she was made a Stohlman Scholar of the Leukemia Lymphoma Society for her work with human hematopoietic (blood-forming) stem and progenitor cells. Her research team’s achievements include:

• Characterization of stem cells in human bone marrow and cord blood
• The first isolation of the primitive cells in cord blood responsible for producing the immune system (Common Lymphoid Progenitors)
• Early demonstration of the use of lentiviral vectors to transfer genes into human hematopoietic stem cells
• Development of a technique to image and track human hematopoietic stem cells after transplantation
• Demonstration that transplanted bone marrow cells can generate cells of pancreas during the neonatal period

Dr. Crooks also is one of the physicians on the Hematopoietic Stem Cell Transplant team at Childrens Hospital Los Angeles.

Donald B. Kohn, MD,  is the leader of the Gene, Immunology and Stem Cell Therapy Program  (GISCT) and heads its Gene Therapy component. He has been an innovator in the field of gene therapy using stem cells for the past 15 years and is an expert in the design and development of gene delivery vectors.  Dr. Kohn led the group that performed the first clinical trial of gene therapy for newborn infants with severe combined immune deficiency ("bubble-baby disease"). His laboratory studies how gene transfer to stem cells can be used to influence how adult and embryonic stem cells grow, differentiate and generate organ-specific tissues, with a particular focus on pancreatic beta cells. 

Dr. Kohn has been the recipient of the Elizabeth Glaser Scientist Award from the Pediatric AIDS Foundation (1995-2000) and a Distinguished Clinical Scientist Award from the Doris Duke Charitable Foundation (2000-2005). He is past president and an advisory board member of the American Society of Gene Therapy.

Carolyn Lutzko, PhD, leads a research team that has been growing human embryonic stem cells (hESC) in the laboratory for more than three years. Her research interests are to further develop an understanding of the basic biology of hESC, to explore the differences between various cell lines and to develop the means to generate blood cells from hESC.  For stem cells to be used in therapy it is essential to understand how the immune system can be generated from hematopoietic stem cells and how it can be manipulated to prevent rejection of transplanted stem cells.

Neena Kapoor, MD, is head of the clinical Hematopoietic Stem Cell Transplant Program at Childrens Hospital Los Angeles. Dr Kapoor has more than 30 years experience in pediatric Bone Marrow Transplantation and, with Ami Shah, MD, oversees the clinical trials in bone marrow transplantation. Translational and clinical research interests of the bone marrow transplant physicians include:

• Purification of stem cells from parents and unrelated donors to remove T cells that can cause Graft versus Host Disease
• Purification of stem cells from bone marrow of children with leukemia to remove contaminating leukemia cells
• Development of less toxic methods to transplant children with genetic diseases

Paula Cannon, PhD,  a virologist, joined the Gene, Immune and Stem Cell Therapy Program in 2003.  Dr. Cannon trained in Oxford, at Harvard University and at the University of Southern California.  Her laboratory works on developing new gene delivery vectors for stem cell modification, as well as more basic aspects of how viruses enter cells.

Punam Malik, MD, is a pediatric hematologist at Childrens Hospital Los Angeles. Her laboratory studies the basic processes by which red blood cells are made from hematopoietic stem cells and how this process goes wrong in sickle cell disease and thalassemia. She has developed novel vectors for gene therapy of these red blood cell diseases and will be initiating clinical trials in the next few years.

Developmental Biology

David Warburton DSc, MD, head of the Developmental Biology Program, has been studying human organ development with more than 25 years of continuous support from the National Institutes of Health (NIH). Dr. Warburton is a boarded specialist in newborn medicine, and so, has a first-hand appreciation of the formation of major organs and organ systems during embryonic development. Dr. Warburton leads a Research Center project on the Molecular Basis of Lung Injury and Repair for the NIH’s National, Heart, Lung and Blood Institute. His research team’s major achievements include the following discoveries:

• Lung organogenesis is driven by finely balanced signaling between families of peptide growth factors and cognate receptors
• Bronchopulmonary dysplasia in human prematures is mediated by excessive signaling by the TGFb class of peptide growth factors
• Discovery and isolation of stem/progenitor cells from lung tissue

Saverio Bellusci, PhD, is an international expert on organogenesis and growth factor signaling. He leads research on lung, gut and breast morphogenesis, the process of differentiation of cells into different tissues or structures. His research team’s major discoveries include the finding that FGF peptide and receptor signaling play a necessary role in lung and gut morphogenesis.

Roger De Filippo, MD, a pediatric urologist, received advanced training in genitourinary tissue engineering in the laboratory of Dr. Anthony Atala at Harvard University. Dr. De Filippo is an expert on bladder, vagina and ureteric engineering using biomatrix as a niche substrate for stem cell engraftment. His laboratory also studies the stem cell potential of cells in amniotic fluid.

Barbara Driscoll, PhD, brings an extensive background in cancer cell cycle research to the team. Over the past five years, she has become well established in the field of lung stem/progenitor cell biology. Her major discoveries include the isolation and characterization of alveolar epithelial stem/progeitor cells from rats using telomerase, cadherins and other markers. She is currently evaluating the role and feasibility of translational research in lung repair and regeneration.

Vesa Kaartinen, PhD,  is an expert mouse geneticist who works on cleft palate and cardiac morphogenesis. His major recent discoveries have involved genetic modification of TGFb signaling in the neural crest lineage to derive mice with Truncus arteriosus and discoveries on the molecular and genetic basis of palatal fusion. His studies have identified a signaling pathway that is required for normal cardiac development and, therefore, is one of the many candidate pathways to be impaired in human subjects suffering from this type of cardiac defects.

J. Denise Tefft, PhD, has advanced expertise on downstream growth factor signaling in organ morphogenesis. Her major achievements have included discovery of the Sprouty gene family as a highly conserved group of inducible negative regulators of growth factor tyrosine kinase signaling, which are key to regulating correct activation of stem/progenitor cells.

Wei Shi, MD, PhD,  is an expert on TGFb family peptide-Smad signaling, BMP inhibitors and membrane sheddases in lung and cardiac morphogenesis and tissue injury and repair. His major recent discoveries have included BMP-Gremlin as key regulators of lung morphogenesis and tissue injury response, and TACE (ADAM12) membrane sheddase and its roles in lung morphogenesis as well as myocardial compaction.

Tai-Lan Tuan, PhD,  is an internationally recognized authority on keloids, a severe form of hypertrophic skin wound healing. She is an expert on the wound protease environment that forms the niche that determines the switch between perfect wound healing in the fetus versus keloids. Her recent discoveries include identifying PAI-1 as a key mediator of the wound niche environment. This may have important implications for the translational application of stem cells to tissue repair.

Victoria Camerini, M.D., is a mucosal immunologist and neonatologist whose research focuses on the development and function of T cells dispersed throughout the intestine called intestinal intraepithelial lymphocytes (IEL).  IEL play key roles in mucosal defense, the regulation of oral tolerance and in epithelial cell growth and repair.  Understanding the life cycle of IEL therefore, has important implications for homeostasis in the gut as well as in the establishment of the mucosal immune system after birth.  In particular, Dr. Camerini’s group is identifying and characterizing T cell progenitors of IEL in the thymus, intestine and in more recent studies, umbilical cord blood.  Her laboratory studies how MHC molecules influence the development and differentiation of T cell progenitors in the establishment of IEL and the mucosal immune system.

Cardiovascular/Tissue Engineering

Ivan Vesely, PhD, is the director of the Cardiovascular Research Program at The Saban Research Institute. His area of expertise is soft tissue biomechanics, particularly in the cardiac valves, with research focusing on experimental and computational mechanics of heart valves and cardiovascular tissue engineering.  Dr. Vesely’s novel approach to tissue engineering is to use mammalian cells as factories for extracellular matrix, whose synthesis and remodeling can be controlled by manipulating the cells and the matrix by external means.  His laboratory has used mesenchymal stem cells, and is exploring the use of human embryonic stem cells, for the production of elastin sheets for vascular tissue reconstruction.

Mary Kearns-Jonker, PhD, studies the immunology of xenograft rejection and the application of gene therapy to induce transplantation tolerance.  Her work included the analysis of immunoglobulin genes used to target transplanted tissues, analysis of the molecular structure of xenoantibody-antigen binding, and the development of small molecules and the use of gene therapy to induce transplant tolerance.  Any residual antigenicity that exists in human embryonic stem cell-derived tissues can thus be addressed with the above approaches.

Cancer

Elizabeth Lawlor, MD, PhD,  is a pediatric oncologist whose research focuses on understanding how cancer-causing genes called oncogenes turn normal cells into malignant cells.  In particular, Dr. Lawlor’s group is interested in the biology of Ewing’s sarcoma and in the isolation and identification of cancer stem cells.  By evaluating how oncogenes disrupt the differentiation and development of normal stem cells she hopes to gain insights into both the origins of pediatric sarcomas and the biology of sarcoma stem cells.  These insights will be critical to the development of cancer stem-cell targeted therapies.