Leadership

Irving L. Weissman, MD, has directed the Institute since its founding, providing vision and leadership to build one of the nation’s top stem cell programs. In 1988, Dr. Weissman became the first to isolate in pure form any stem cell in any species when he isolated the hematopoietic or blood-forming stem cell in mice. He subsequently isolated the human hematopoietic stem cell, the human neuronal stem cell, and the human leukemia stem cell. His work has opened up an entirely new area of scientific research with enormous potential for life-saving therapies.

Dr. Weissman recently made an exciting step toward the goal of transplanting adult stem cells to create a new immune system for people with autoimmune or genetic blood diseases. As published in the November 2007 issue of Science, his lab found a novel way to transplant new blood-forming stem cells into the bone marrow of mice without the tissue-damaging radiation or chemotherapy usually required, thereby effectively replacing their immune systems. Many aspects of this technique will need to be adapted before it can be tested in humans, but when those barriers are surmounted, the benefits could be significant. An immune system transplant, much like a liver or heart transplant, would give a person with an autoimmune disease, such as multiple sclerosis, hope for a healthy future.

Dr. Weissman received his medical degree from Stanford in 1965 and, after carrying out research in laboratories provided by the late Henry S. Kaplan, MD, joined the faculty four years later. In addition to being the Virginia and D. K. Ludwig Professor for Clinical Investigation in Cancer Research, he is a professor of pathology and developmental biology, and, by courtesy, professor of neurosurgery and of biological sciences.

Dr. Michael T. Longaker has broad experience in pediatric plastic surgery, developmental biology, epithelial biology, tissue repair and tissue engineering. He has extensive research experience in the cellular and molecular biology of extracellular matrix, with specific applications to the differences between fetal and post-natal wound healing, the biology of keloids and hypertrophic scars and the cellular and molecular events that surround distraction osteogenesis with respect to craniofacial development. Most recently, his research has focused on multipotent mesenchymal cells derived from adipose tissue and their applications for tissue repair, replacement and regeneration. He brings to Stanford his unique understanding of wound healing, fetal wound healing research, developmental biology and tissue engineering.

Dr. Longaker earned his undergraduate degree at Michigan State University, (where he played varsity basketball and was a member of the 1979 NCAA Men’s Basketball Championship Team) and his medical degree at Harvard Medical School. He completed his surgical residency at the University of California, San Francisco, a residency in Plastic Surgery at NYU and a craniofacial fellowship at UCLA. The majority of his research training took place while he was a Post Doctoral Research Fellow in the Fetal Treatment Program under Dr. Michael Harrison and in the laboratory of Dr. Michael Banda in Radiobiology, both at UCSF. In December 2003, Dr. Longaker earned his MBA from University of California – Berkeley and Columbia University, in the inaugural class of their combined program. He was elected into Beta Gamma Sigma at Columbia Business School.

Dr. Maria Grazia Roncarolo is a pioneer in cell and gene therapy for genetic diseases and a world-renowned expert in immune regulation. Her breakthrough translational research intersects two distinct but interrelated areas: inducing immune tolerance following hematopoietic stem cell and progenitor cell transplantation (HSPCT) and designing novel gene and cell therapy approaches for patients with inborn errors of immunity and hematological malignancies.

Dr. Roncarolo discovered a subset of inducible regulatory T cells called type 1 regulatory T (Tr1) cells, which she brought into the clinic to support hematopoietic stem and progenitor cell (HSPC) engraftment and prevent graft-versus-host disease (GvHD), a major complication of otherwise life-saving allogeneic HSCT. She was the principal investigator for the first clinical trial using in vitro generated donor-derived Tr1 cells in adult leukemia patients undergoing haploidentical HSCT. Dr. Roncarolo is now the Sponsor of a new clinical trial (NTC03198234), in which patient alloantigen-specific Tr1 cells, called T-allo10, are infused to prevent GvHD in patients with hematological malignancies receiving allogeneic HSPCT. During this time, Dr. Roncarolo is also conducting pre-clinical studies on a 2^ndgeneration of Tr1 cells, made by lentiviral insertion of the IL10 gene into human CD4⁺ T cells. Along with immunosuppressive properties, these engineered Tr1 cells are active against malignant myeloid cells, and are being explored as a potential novel cell therapy for acute myeloid leukemia (AML).

In addition, Dr. Roncarolo successfully led the first stem cell-based gene therapy trial for severe combined immunodeficiency (SCID) patients lacking adenosine deaminase (ADA-SCID; “bubble boy disease”), a life-threatening inborn error of immunity. The treatment, combining gene-corrected blood stem cells with low-dose chemotherapy, obtained orphan drug status from the FDA and EMEA. It was subsequently licensed to GlaxoSmithKline (GSK) as Strimvelis. This milestone in gene therapy was integral in the implementation of stem cell and gene therapies for other severe inherited diseases, including Wiskott-Aldrich syndrome (WAS) and metachromatic leukodystrophy (MLD). Currently, Dr. Roncarolo is designing a gene therapy strategy to correct mutations in IL-10 and IL-10 receptor genes, which cause devastating very early onset inflammatory bowel disease (VEO-IBD), by CRISPR-based gene correction of patient HSPCs.

At Stanford University School of Medicine, Dr. Roncarolo is a faculty member in the Pediatric Division of Stem Cell Transplantation and Regenerative Medicine, Co-Director of the Institute for Stem Cell Biology and Regenerative Medicine (ISCBRM), and Director of the Center for Definitive and Curative Medicine (CDCM).  As the founder of the CDCM, Dr. Roncarolo continues to lead clinical translation of cell and gene therapy approaches aimed at curing patients with incurable diseases. Dr. Roncarolo has more than 300 peer-reviewed publications and has received numerous honors  (see CAP profile), while also successfully mentoring over 20 students and postdoctoral scholars and has received numerous honors. Dr. Roncarolo is currently leading a small but vibrant lab comprised of three post-doctoral fellows, one graduate student in the Stem Cell Biology program, two life-science research professionals, one CIRM scholar and one Instructor of Pediatrics.

Center for Definitive and Curative Medicine

Roncarolo Lab Website

In addition to his clinical duties in the division of Oncology, Michael F. Clarke, MD, maintains a laboratory focused on stem cells and the role they play in cancer. Dr. Clarke’s research is aimed at the identifications and characterization of cancer stem cells, and at increasing our knowledge of the factors that control self-renewal in normal stem cells and their malignant counterparts. A central issue in stem cell biology is increasing our understanding the mechanisms that regulate self-renewal of hematopoietic stem cells, which are required for the renewal of the blood supply over a lifetime. Dr. Clarke’s laboratory found a key gene that regulates this process, and is now investigating how the regulatory gene itself is regulated. Dr. Clarke was the first researcher to find cancer stem cells in a solid tumor (a breast cancer) and discovered that the inhibition of programmed cell death is essential for the growth of breast cancers. He also has found certain gene activity signatures that predict whether breast cancer will recur after treatment. Dr Clarke’s research has important implications for the detection, characterization and treatment of human cancers.

After receiving his MD degree from Indiana University, Dr. Clarke was an Oncology Fellow at the National Cancer Institute. In 1986, he joined the faculty at the University of Michigan where he was a Professor of Internal Medicine and a Professor of Cell and Developmental Biology. In the fall of 2005 Dr. Clarke will move to Stanford University where he will direct the solid tumor cancer stem cell program and serve as Deputy Director of the Institute for Stem Cell Biology and Regenerative Medicine.