Stem Cell Biology and Technology
Chris Amemiya, PhD (Biology; Genetics Program at Benaroya Research Institute)
Dr. Amemiya is a developmental geneticist, who uses comparative genomics approaches to study evolutionary and developmental aspects of the vertebrate adaptive immune system and the development of morphological structures. The lab is actively utilizing and is involved in construction and utilization of bacterial artificial chromosome (BAC) reagents and developing ways in which to employ BACs for functional biology and for making inferences relevant to human medicine.
Norman Beauchamp (Chair of Radiology)
I am finalizing the recruit of a faculty from Hopkins that will bring skills in working with stem cells with the goal of them joining the SLU team. We have developed and are performing studies monitoring stem cell movement. We have recruited a scientist to develop smart contrast agents to enhance our ability to track stem cells. It is a big part of where I am taking the department in terms of molecular imaging and diagnostics.
Jim Bruce (Genome Sciences)
Our research interests include proteomics, mass spectrometry and advanced technology development, mapping protein interactions and topologies in biological systems and chemical biology. We are developing new mass spectrometry technology and chemical approaches that allow insight in protein interaction networks in vivo.
Michael T. Chin, MD, PhD (Medicine/Cardiology)
I am interested in several questions regarding regeneration of the heart. Specifically, I am interested in identifying and characterizing genes that promote the differentiation of stem cells into heart and vascular cells; identifying ways to promote the maturation of immature cardiac cells into mature and functional cardiac cells, and in identifying ways to convert existing fibroblasts into mature cardiac cells. Ultimately we hope to develop a personalized medicine approach where patient derived cells can be harvested and banked for future use in regenerating damaged hearts.
Mark Cooper (Biology)
During early embryogenesis, embryonic cell populations within vertebrate embryos exhibit extraordinary sequences to transient, stereotyped morphogenetic behaviors. The Cooper laboratory seeks to understand how these genetically encoded cell behaviors are organized spatiotemporally to generate embryonic tissues in living embryos through the use of computer-assisted imaging and visualization approaches.
Cole A. DeForest, PhD (Chemical Engineering)
While the potential for biomaterial-based strategies to improve and extend the quality of human health through tissue regeneration and the treatment of disease continues to grow, the majority of current strategies rely on outdated technology initially developed and optimized for starkly different applications. Therefore, the DeForest Group seeks to integrate the governing principles of rational design with fundamental concepts from material science, synthetic chemistry, and stem cell biology to conceptualize, create, and exploit next-generation materials to address a variety of health-related problems. We are currently interested in the development of new classes of user-programmable hydrogels whose biochemical and biophysical properties can be tuned in time and space over a variety of scales. Our work relies heavily on the utilization of cytocompatible bioorthogonal chemistries, several of which can be initiated with light and thereby confined to specific sub-volumes of a sample. By recapitulating the dynamic nature of the native tissue through 4D control of the material properties, these synthetic environments are utilized to probe and better understand basic cell function as well as to engineer complex heterogeneous tissue.
Zhijun Duan, PhD (Medicine/Hematology)
The focus of our research is on understanding the mechanisms underlying development and tumorigenesis through deciphering the structure-function relationship of mammalian genomes. We have developed a series of high throughput methods for mapping three-dimensional (3D) genome architecture globally or locally. Recently, in collaboration with the investigators in the University of Washington Center for Nuclear Organization and Function (UW-CNOF), we developed a single-cell Hi-C method for characterize the 3D genome architecture in thousands of single cells in a massively parallel fashion. We have used these tools to dissect the dynamics of 3D genome organization in the context of a variety of biological systems. One of our current focuses is to characterize the nuclear morphology-associated 3D genome rearrangement and epigenetic programming during blood cell maturation and the pathogenesis of hematologic disorders.
Benjamin Freedman, PhD (Nephrology)
Our laboratory has developed techniques to efficiently differentiate hPSCs into kidney organoids in a reproducible, multi-well format – a prototype ‘kidney-in-a-dish’. In addition, we have generated hPSC lines carrying naturally occurring or engineered mutations relevant to human kidney diseases, such as polycystic kidney disease and nephrotic syndrome. The goal of our research is to use these new tools to model human kidney disease and identify therapeutic approaches, including kidney regeneration.
Cecilia Giachelli (Bioengineering)
My lab is interested in applying stem cell and regenerative medicine strategies to the areas of ectopic calcification, tissue engineering, biomaterials development and biocompatibility.
Jay Heinecke (Medicine/Metabolism, Endocrinology & Nutrition)
The Heinecke laboratory provides state-of-the-art proteomic analyses to investigators with an interest in stem cell biology.
Marshall Horwitz (Pathology)
The Horwitz laboratory has a longstanding interest in genes and mechanisms leading to hematological malignancy. More recently, the lab has focused attention on using somatic mutations to infer cell lineage in order to better understand how stem cells contribute to development, tissue regeneration, and cancer.
Deok-Ho Kim (Bioengineering)
Through the use of multiscale fabrication and integration tools, Dr. Kim's research focuses on the development and applications of biomimetic cell culture models and functional tissue engineering constructs for high-throughput drug screening, stem cell-based therapies, disease diagnostics, and medical device development.
David L. Mack (Rehabilitation Medicine)
The Mack laboratory combines stem cell and gene therapies to develop new treatments for neuromuscular diseases. Induced pluripotent stem cell technology is used to generate patient-specific stem cells that can undergo directed-differentiation to multiple lineages in culture. Three-dimensional scaffolds are also being employed to further differentiate each cell type into their more mature form. This so called “disease-in-a-dish” approach will enable us to study disease mechanisms, and to create novel drug discovery platforms. Drugs identified in this way are likely to work in the patient since the patient’s own cells were used as the screening tool. Diseases being explored include Duchenne muscular dystrophy, X-linked myotubular myopathy and autistic syndrome disorder.
Dr. Mack is a classically trained geneticist with expertise in developmental and stem cell biology. During his postdoctoral fellowship at the National Cancer Institute, he studied how the stem cell microenvironment controls cell fate during mammary gland development. His recent contributions to the field of regenerative medicine center on the interplay between a cell’s genetic program and it microenvironment during lineage commitment.
Mark W. Majesky, PhD (Seattle Children's Hospital)
My laboratory studies the origins and differentiation of stem and progenitor cells in the developing heart and blood vessel wall. We employ a variety of genetic, cell and molecular biology approaches to dissect the molecular mechanisms that produce and maintain cardiac and vascular wall progenitor cells in the embryo. Our current work focuses on two projects: (1) the role of sonic hedgehog signaling in the proliferation and survival of a novel population of resident vascular progenitor cells in the adventitial layer of artery wall, and (2) the opposing roles of notch signaling and receptor tyrosine kinase-dependent pathways in control of coronary vessel formation from progenitor cells in the proepicardium. We are evaluating two potent transcriptional silencers that we believe play critical roles in the specification and maintenance of vascular progenitor cells, namely Klf4 (adventitial progenitors) and Tbx18 (proepicardial progenitors).
Daniel G. Miller, MD, PhD (Pediatrics)
Dr. Miller and members of his research group utilize induced pluripotent stem cells (IPSc) made from the skin cells of individuals with Facioscapulohumeral Muscular Dystrophy (FSHD) to understand the etiology of this debilitating condition. The hypothesis is that FSHD is caused by a defect in muscle development and/or maintenance so studying differences between control and patient embryonic cells as they differentiate to form muscle may reveal key mechanisms of disease pathology. Dr. Miller is also interested in treatment strategies for genetic conditions so members of his research group use vectors based on Adeno-Associated Virus (AAV) to perform gene targeting in primary human cells. This approach is currently being applied to keratinocytes from patients affected with a skin blistering condition called Epidermolysis Bullosa. The molecular consequence of disease-causing mutations can also be studied by creating the same mutations in primary human cells, or correcting mutations in cells from affected patients.
Dr. Miller also sees patients with genetic conditions in the pediatric medical genetics clinic at Children's Hospital.
Satoshi Minoshima (Radiology)
Dr. Minoshima has been developing magnetic resonance (MR) and positron emission tomography (PET) imaging of neuro-progenitor cells and gene / drug delivery vehicles. He has an extensive background in imaging sciences and research and clinical applications to animals and humans.
Ray Monnat, PhD (Pathology, Genome Sciences)
Our research focuses on human RecQ helicase deficiency syndromes such as Werner syndrome; high resolution analyses of DNA replication dynamics; and the engineering of homing endonucleases for targeted gene modification or repair in human and other animal cells.
Thalia Papayannopoulou, PhD (Medicine/Hematology)
Dr. Thalia Papayannopoulou's research program aims to understand the mechanisms whereby hematopoietic stem cells home to bone marrow following transplantation, and how they traffic between the marrow and the blood stream under normal and perturbed hematopoiesis. A particular focus is on the characterization of the hematopoietic stem cell niche. In addition, Papayannopoulou lab studies erythroid cell development during the embryonic, fetal and adult stages of development.
Drew L. Sellers, PhD (Bioengineering)
Despite possessing a resident pool of neural stem cells, the mammalian brain and spinal cord shows a limited ability to regenerate damaged tissue after traumatic injury. Instead, injury initiates a cascade of events that direct reactive gliosis to wall off an injury with a glial scar to mitigate damage and preserve function. My current research interests explore approaches to re-engineer the stem cell niche, to utilize gene-therapy and genome editing approaches to reprogram and engineer stem cells directly, and to enhance drug delivery into the central nervous system (CNS) to drive regenerative strategies that augment functional recovery in the diseased or traumatically injured CNS.
Nathan Sniadecki, PhD (Mechanical Engineering)
Our mission is to understand how mechanics affects human biology and disease at the cellular level. If we can formulate how cells are guided by mechanics, then we can direct cellular response in order to engineer cells and tissue for medical applications. We specialize in the design and development of micro- and nano-tools, which allows us to probe the role of cell mechanics at a length scale appropriate to the size of cells and their proteins.
Kelly R. Stevens, PhD (Bioengineering, Pathology)
Our research is focused on developing new technologies to assemble synthetic human tissues from stem cells, and to remotely control these tissues after implantation in a patient. To do this, we use diverse tools from stem cell biology, tissue engineering, synthetic biology, microfabrication, and bioprinting. We seek to translate our work into new regenerative therapies for patients with heart and liver disease.
Rong Tian (Anesthesiology & Pain Medicine, Bioengineering)
My lab is interested in the role of mitochondria and cell metabolism in cell differentiation and in particular, in the maturation of cardiac myocytes.
Keiko Torii (Biology)
Signals that specify terminal differentiation of stomatal stem cells.
Valera Vasioukhin (Fred Hutch)
Our laboratory studies the mechanisms and significance of cell polarity and cell adhesion in normal mammalian development and cancer.
Jakob von Moltke, PhD (Immunology)
We are generally interested in the initiation of immune responses by parasitic worms and allergens, and the tissue remodeling that is a hallmark of this “type 2” inflammation. We recently discovered that type 2 immune responses in the small intestine require a specialized epithelial lineage called tuft cells. Tuft cells are normally very rare, but during type 2 inflammation the cytokine IL-13 signals in epithelial stem cells to bias their lineage commitment towards tuft cells and the mucus-secreting goblet cells, leading to dramatic changes in the cellular composition of the intestinal lining. Using genetic mouse models combined with imaging, flow cytometry, and organoid tissue culture, we are investigating the stem cell differentiation pathways that give rise to tuft and goblet cells in the intestine, with the goal of understanding how IL-13 alters cellular fate decisions.
Yuliang Wang, PhD (Computer Science & Engineering)
Pluripotent stem cell differentiation and tissue development are often accompanied by significant metabolic shifts. It is increasingly recognized that metabolic states are not merely the byproduct of cellular signaling, but can actively influence cell fate decision. In particular, cellular epigenetic states (histone and DNA methylation, histone acetylation) and intermediary metabolism are interconnected by key metabolites such as S-Adenosyl methionine, α-ketoglutarate, acetyl-CoA. My research aims to integrate transcriptomics, epigenetics and network modeling to understand the how metabolic network state influences stem cell differentiation and tissue development via its effects on epigenetic modifications. This research can lead to efficient metabolic approaches (changing medium culture, inhibiting or activating a metabolic enzyme) to manipulate cell fates.
Carol Ware (Comparative Medicine)
Director of the Human Embryonic Stem Cell Core (hESC Core). Research includes studies of human embryonic stem cell self-renewal to maintain normal phenotype and genotype following extended in vitro culture. She is internationally known for developing successful methods for freezing and restarting stem cells and for comparative studies on existing hESC lines.
Thomas N. Wight, PhD (Benaroya Research Institute)
This investigator leads a research program focused on the role that the extracellular matrix molecules, proteoglycans and hyaluronan, play in regulating vascular cell type and the regulation of extracellular matrix assembly. These pathways are fundamental to understanding the growth of new blood vessels in different tissues of the body, and have potential for direct tissue regeneration applications through the use of proteoglycan genes to bioengineer vascular tissue.
Norm Wolf (Pathology)
Stem cell location and identity of the lens epithelium; The role of Sirt1 in lens metabolism and replication; The gene message expressions of the central zone of the lens and, separately, of the germinative zone that is lateral to it. The identity and changes with aging of the repair enzymes active in repair after oxidative damage to the lens epithelium.
Wenqing Xu (Biological Structure)
This lab works on the structural biology of Wnt pathway components that regulate stem cell proliferation and differentiation.
Alejandro Wolf-Yadlin (Genome Sciences)
The main focus of our lab is on the application of systems biology to the study of cancer. We develop proteomics tools to study cellular signaling dynamics and topology. We then apply these tools in conjunction with gene expression, epigenetic and phenotypic analyses of cellular systems to understand molecular and behavioral characteristics of cancer primary cells and cancer stem cells. The ultimate goal of our researcStemh is to identify molecular signatures of cancer progression that can illuminate potential drug targets as well as be utilized as diagnostic tools for early cancer detection.
Chun Yuan (Pathology)
Imaging, as already identified as a core of the institute, can play key roles in many different areas in stem cell research. One apparent area would be to monitor the therapeutic effects in tissue function as in the treatment of stroke, multiple sclerosis, spinal cord injuries, liver disease, and pancreatic islet cell transplantation. The most advanced area of research involves the use of stem cells to treat heart conditions, including the repair of myocardium after infarction. Most of the current works are in varies animal models but can be extended into human imaging. Stem cell tracking by invasive and non-invasive imaging is also being developed as part of the overall efforts in molecular imaging. This capability will be beneficial.
Ying Zheng, PhD (Bioengineering)
Dr. Zheng's research focuses on understanding and engineering the fundamental structure and functions in living tissue and organ systems from nanometer, micrometer to centimeter scale.