Institute for Stem Cell Biology and Regenerative Medicine
Showing 21-30 of 37 Results
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Yusuke Nakauchi
Instructor, Institute for Stem Cell Biology and Regenerative Medicine
Current Research and Scholarly InterestsFrom 2005 to 2010, my work as a clinical hematology fellow allowed me to experience first-hand how scientific advances that started in a laboratory can transform patients' lives. While many of my patients were cured of their disease with allogeneic hematopoietic stem cell transplantation, underscoring the importance of anti-tumor immunotherapy in eradicating leukemia, I witnessed face-to-face their suffering from the long-term consequence of graft-versus-host disease (GVHD). This experience was ultimately what drove me to engage in research to discover novel therapies. For this reason, I embarked on a Ph.D. program in 2010 to design antibody therapy to (i) target GVHD and (ii) target hematological malignancies. Under the mentorship of Professor Hiromitsu Nakauchi at the University of Tokyo, an international leader in hematopoiesis, I developed allele-specific anti-human leukocyte antigen (HLA) monoclonal antibodies for severe GVHD caused by HLA-mismatched hematopoietic stem cell transplantation (Nakauchi et al., Exp Hematol, 2015). This study was the first to find that anti-HLA antibodies can be used therapeutically against GVHD. That success gave me the motivation and confidence to further my research beyond targeting GVHD to targeting leukemic stem cells through my postdoctoral fellowship in the laboratory of Professor Ravindra Majeti here at Stanford University.
Many people suffer from leukemia each year, but we still don't know how to cure it completely. Recent advances in sequencing technologies have tremendously improved our understanding of the underlying mutations that drive hematologic malignancies. However, the reality is that most of the mutations are not easily "druggable," and the discovery of these mutations has not yet significantly impacted patient outcomes. This is perhaps the most crucial challenge facing a translational cancer researcher like myself. My current research is a major step toward my long-term goal of making personalized medicine a reality for patients with acute myeloid leukemia (AML) and other hematologic malignancies.
Since joining the Majeti lab, I have been targeting the ten-eleven translocation methylcytosine dioxygenase-2 (TET2) mutation, which is aberrant in leukemia at a high rate and has been studied using human-derived cells. TET2 is known to be involved in the clonal expansion of cells, and people with this mutation are more likely to suffer from hematologic malignancies. It is also known to be involved in the development of coronary artery disease, a gene that has attracted much attention in recent studies. In my field, it is an essential gene involved in the abnormal proliferation of hematopoietic stem cells. Focusing on this gene, I mapped TET2-dependent 5hmC, epigenetic and transcriptional programs matched to competitive advantage, myeloid skewing, and reduced erythroid output in TET2-deficient hematopoietic stem and progenitor cells (HSPC). Vitamin C and azacitidine restore the 5hmC landscape and phenotypes in TET2-mutant HSPCs. These findings offer a comprehensive resource for TET-dependent transcriptional regulation of human hematopoiesis and shed light on the potential mechanisms by which TET deficiency contributes to clonal hematopoiesis and malignancies. Of course, these findings would also be of value in understanding the biology of normal hematopoietic stem cells (HSCs) and various other TET2-related cancers.
And from now on, I would like to use the single-cell transplantation techniques mastered in the Majeti lab to study the behavior of normal and aberrant human HSCs using various new methods, ultimately preventing the progression of AML.
In my clinical experience, I have lost many AML patients. With the regret and sadness of losing these patients in my heart, I hope to one day contribute to developing treatments that will fundamentally change how the world treats leukemia. -
Aaron Newman
Assistant Professor of Biomedical Data Science
Current Research and Scholarly InterestsOur group develops computational strategies to study the phenotypic diversity, differentiation hierarchies, and clinical significance of tumor cell subsets and their surrounding microenvironments. Key results are further explored experimentally, both in our lab and through collaboration, with the ultimate goal of translating promising findings into the clinic.
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Roeland Nusse
Virginia and Daniel K. Ludwig Professor of Cancer Research
Current Research and Scholarly InterestsOur laboratory studies Wnt signaling in development and disease. We found recently that Wnt proteins are unusual growth factors, because they are lipid-modified. We discovered that Wnt proteins promote the proliferation of stem cells of various origins. Current work is directed at understanding the function of the lipid on the Wnt, using Wnt proteins as factors the expand stem cells and on understanding Wnt signaling during repair and regeneration after tissue injury.
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Lucy Erin O'Brien
Associate Professor of Molecular and Cellular Physiology
Current Research and Scholarly InterestsMany adult organs tune their functional capacity to variable levels of physiologic demand. Adaptive organ resizing breaks the allometry of the body plan that was established during development, suggesting that it occurs through different mechanisms. Emerging evidence points to stem cells as key players in these mechanisms. We use the Drosophila midgut, a stem-cell based organ analogous to the vertebrate small intestine, as a simple model to uncover the rules that govern adaptive remodeling.
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Anthony Oro, MD, PhD
Eugene and Gloria Bauer Professor
Current Research and Scholarly InterestsOur lab uses the skin to answer questions about epithelial stem cell biology, differentiation and carcinogenesis using genomics, genetics, and cell biological techniques. We have studied how hedgehog signaling regulates regeneration and skin cancer, and how tumors evolve to develop resistance. We study the mechanisms of early human skin development using human embryonic stem cells. These fundamentals studies provide a greater understanding of epithelial biology and novel disease therapeutics.
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Theo Palmer
Professor of Neurosurgery, Emeritus
Current Research and Scholarly InterestsMembers of the Palmer Lab study the biology of neural stem cells in brain development and in the adult. Our primary goal is to understand how genes and environment synergize in influencing stem cell behavior during development and how mild genetic or environmental risk factors for disease may synergize in their detrimental effects on brain development or in the risk of neuronal loss in age-related degenerative disease.
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Matthew Porteus
Sutardja Chuk Professor of Definitive and Curative Medicine
BioDr. Porteus was raised in California and was a local graduate of Gunn High School before completing A.B. degree in “History and Science” at Harvard University where he graduated Magna Cum Laude and wrote an thesis entitled “Safe or Dangerous Chimeras: The recombinant DNA controversy as a conflict between differing socially constructed interpretations of recombinant DNA technology.” He then returned to the area and completed his combined MD, PhD at Stanford Medical School with his PhD focused on understanding the molecular basis of mammalian forebrain development with his PhD thesis entitled “Isolation and Characterization of TES-1/DLX-2: A Novel Homeobox Gene Expressed During Mammalian Forebrain Development.” After completion of his dual degree program, he was an intern and resident in Pediatrics at Boston Children’s Hospital and then completed his Pediatric Hematology/Oncology fellowship in the combined Boston Chidlren’s Hospital/Dana Farber Cancer Institute program. For his fellowship and post-doctoral research he worked with Dr. David Baltimore at MIT and CalTech where he began his studies in developing homologous recombination as a strategy to correct disease causing mutations in stem cells as definitive and curative therapy for children with genetic diseases of the blood, particularly sickle cell disease. Following his training with Dr. Baltimore, he took an independent faculty position at UT Southwestern in the Departments of Pediatrics and Biochemistry before again returning to Stanford in 2010 as an Associate Professor. During this time his work has been the first to demonstrate that gene correction could be achieved in human cells at frequencies that were high enough to potentially cure patients and is considered one of the pioneers and founders of the field of genome editing—a field that now encompasses thousands of labs and several new companies throughout the world. His research program continues to focus on developing genome editing by homologous recombination as curative therapy for children with genetic diseases but also has interests in the clonal dynamics of heterogeneous populations and the use of genome editing to better understand diseases that affect children including infant leukemias and genetic diseases that affect the muscle. Clinically, Dr. Porteus attends at the Lucille Packard Children’s Hospital where he takes care of pediatric patients undergoing hematopoietic stem cell transplantation.
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Kristy Red-Horse
Professor of Biology
Current Research and Scholarly InterestsCardiovascular developmental biology
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Maria Grazia Roncarolo
George D. Smith Professor of Stem Cell and Regenerative Medicine and Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)
Current Research and Scholarly InterestsResearch Interests
Immunetolerance: Mechanisms underlying T-cell tolerance, induction of T-cell anergy and regulatory T cells; Immunomodulation: mAbs, proteins and low molecular weight compounds which can modulate T-cell activation; Primary immunodeficiencies: Characterization of molecular and immunological defects; Gene therapy: Gene transduction of hematopoietic cells for gene therapy in primary immunodeficiencies and metabolic diseases; Hematopoiesis: Mechanisms underlying growth and differentiation of hematopoietic stem cells; Transplantation: Immune reconstitution and T-cell tolerance after allogenic stem cell transplantation; Cytokines/Cytokine receptors: Role in regulation of immune and inflammatory responses
Clinical Interests
Primary Immunodeficiencies
Monogenic Autoimmune Disorders
Allogenic Bone Marrow Transplantation
Gene Therapy Clinical Trials
Cell Therapy Clinical Trials
Clinical Trials in Autoimmune Diseases and Organ Transplantation
Clinical Trials in Hemoglobinopathies -
Vittorio Sebastiano
Associate Professor (Research) of Obstetrics and Gynecology (Reproductive and Stem Cell Biology)
Current Research and Scholarly InterestsThe thread of Ariadne that connects germ cells, preimplatation development and pluripotent stem cells is the focus of my research, with a specific interest in human development. My long-term goals are: 1. Understanding the biology of germ cells and and their ability to sustain early preimplantation development; 2. Understanding the mechanisms that regulate very early cell fate decisions in human embryos; 3. Understanding the biology of derivation and maintenance of Pluripotent Stem Cells