Karin Bornfeldt, PhD (Metabolism, Endocrinology and Nutrition and Pathology)
The goal of the Bornfeldt laboratory is to increase our understanding of the mechanisms causing cardiovascular complications of diabetes and the metabolic syndrome, and to find novel treatment strategies to combat these complications in patients. In relation to this overall goal, we are investigating the effects of diabetes and metabolic syndrome on hematopoietic stem cells in mechanistic mouse models. Another project in the lab, conducted in collaboration with Dr. Charles Murry, is focused on the effect of diabetes on myocardial infarction in mouse models and potential repair by stem cell-mediated approaches. Finally, Dr. Bornfeldt directs a Diabetes Research Center core facility (https://depts.washington.edu/diabetes/vtmc) together with Dr. Dan Miller. This core provides CRISPR services in stem cells in collaboration with ISCRM.
Jeff Chamberlain, PhD (Neurology, Biochemistry and Medicine/Medical Genetics)
Our Center is focused on developing a gene therapy-based treatment for the muscular dystrophies. Our investigators have published results showing the ability to halt muscular dystrophy and achieve a significant extension of lifespan in adult mice with dystrophy, the first group in the words to accomplish such a feat. Members of our Center have also recently received an NIH program project grant to develop stem cell based therapies for the muscular dystrophies, and have made pioneering studies of a new type of adult muscle stem cell.
Several unique features of the Seattle area have combined to enable the development of the world renowned excellence in muscular dystrophy research. As mentioned, we have an extremely large group of physicians and scientists working together on the disease. In addition, the Seattle area has one of the largest concentrations of scientists working on the development of gene therapy for many different diseases, and the expertise of those gene therapists has directly stimulated our own work on muscular dystrophy. Also, the UW has one of the few University operated Cell and Gene Therapy Laboratories, locate din our hospital to facilitate clinical trials of cell and gene therapies. Finally, the Seattle area is also well known for pioneering work in stem cell technologies, particularly in the hematopoietic stem cell fields, and the large number of labs working on stem cells has also greatly facilitated the newer work on muscle stem cells. Partly in recognition of the importance and depth of the cell and gene therapy work on muscular dystrophy in Seattle, Dr. Chamberlain, the director of the Seattle Muscular Dystrophy Research center has been named a member of the Food and Drug Administration’s Cellular, Tissue and Gene Therapies Advisory Committee for the Center for Biologics Evaluation and Research, is a member of the Scientific Advisory board of the National Gene Vector labs.
Finally, another feature of the Seattle area that facilitated the push for gene therapy trials of muscular dystrophy is that the American Society for Gene therapy (ASGT) was founded by the UW’s Dr. George Stamatoyannopoulos, and at least 5 faculty members at the UW and FHCRC have served on the board of directors of the ASGT.
Jennifer Davis, PhD (Pathology, Bioengineering)
The Davis lab studies how the heart heals and remodels in response to acquired and genetic diseases. Because of the heart’s limited regenerative capacity, an injury or chronic disease results in permanent fibrotic scarring, which in turn creates an environment hostile to regeneration and cellular therapies. Through the use of mouse genetics and a variety of interdisciplinary experimental approaches our research is focused on elucidating the cellular and molecular underpinnings of cardiac remodeling. Specifically, this research program is focused on 2 primary areas which include (1) identifying the signaling networks causal for cardiac fibroblast differentiation into the cell-type (myofibroblast) that is causal for fibrosis and (2) identifying the mechanical signaling that determines cardiac myocyte directional growth leading to a hypertrophic or dilated heart. This research agenda will significantly inform the field’s understanding of fibroblast and myocyte biology as well as cardiac remodeling, which could significantly impact both drug development and the current clinical paradigms for treating acquired and genetic heart disease.
David A. Dichek, MD (Medicine/Cardiology)
Our work focuses on defining the molecular mechanisms that drive aortic aneurysm formation and that precipitate atherosclerotic plaque rupture (the proximal cause of most heart attacks). We are also developing a gene therapy—delivered to the blood vessel wall—that prevents and reverses atherosclerosis. Experiments are performed in a mouse model of heritable thoracic aortic aneurysms, a mouse model of atherosclerotic plaque rupture, and with advanced human plaque tissue. Our gene therapy research uses helper-dependent adenoviral vectors to test therapies in rabbit models of carotid artery and vein graft atherosclerosis. We anticipate that insights from our work will lead to therapies that prevent or stabilize aortic aneurysms and that prevent and reverse atherosclerosis.
Hongxia Fu, PhD (Medicine/Hematology)
Our lab develops and applies single molecule biophysical methods to directly capture nanoscale events in biological processes such as protein folding/unfolding and biomolecular interactions, and explore the underlying molecular mechanisms in order to unveil the origin of disease. We also use human pluripotent stem cells to re-create key features of human vascular disease, such as thrombosis and bleeding disorders. Combining single-molecule manipulation tools, microfluidics, and stem cell biology, we are building a molecule-to-tissue scale model of human disease and aim to develop novel interventions, including both molecular and cellular therapies.
Ken Fujise, MD (Internal Medicine)
Our team has focused on fortilin, a 172-amino acid polypeptide with multiple biological functions. Fortilin binds p53, a tumor suppressor protein, and prevents it from transcriptionally activating its target pro-apoptotic genes, such as BAX and PUMA. In addition, fortilin negatively regulates IRE1α, an ER-stress handling molecule and protects cells against ER-stress induced apoptosis. Fortilin fortifies cells against oxidative stress by binding and keeping peroxiredoxin-1 (PRX1) from inactivated by phosphorylation. We are interested in the role of fortilin in stem cell preservation and differentiation. We hope to use fortilin, through gene transfer and other overexpression strategies, to preserve and maximally utilize various stem cells to treat chronic human diseases, such as heart failure, Alzheimer’s disease, and diabetes mellitus.
Cecilia Giachelli, PhD (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.
Stephen Hauschka, PhD (Biochemistry)
This lab studies developmental mechanisms responsible for directing mesodermal cells toward the skeletal and cardiac muscle cell lineages, and they work with the natural stem cells (satellite cells) of adult skeletal muscle that are responsible for muscle repair.
Shin Lin, MD, PhD, MHS (Medicine/Cardiology)
The Lin Lab is interested in understanding the epigenomic changes which occur in cardiovascular disease states. The lab employs the latest in second generation sequencing methods to identify various regulatory elements on a global scale on human samples collected from the operating room. Generated data are subsequently analyzed in the context of other big data from public repositories on a computer cluster. High throughput methods involving stem cell differentiated cardiomyocytes are employed for subsequent in vitro validation. Murine models are also utilized to study key genes within a physiological framework. The research of the lab thus involves procurement of samples in the clinical setting, computational biology, statistics, molecular biology, stem cell culturing, and mouse work. By exploring the epigenomic changes of cardiovascular disease states, the hope is that new avenues for therapies will be discovered.
David L. Mack, PhD (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.
William M. Mahoney, Jr., PhD (Pathology)
Dr. Mahoney is a researcher in the Center of Cardiovascular Biology and Regenerative Medicine at the UW South Lake Union campus. Research in the Mahoney laboratory is centered on understanding the basic mechanism controlling cell differentiation. Areas of focus include: (1) the characterization of specific molecular signatures defining different vascular beds; (2) determination of the mechanism by which Regulator of G-protein Signaling (RGS) proteins mediate smooth muscle cell physiology during development and in response to disease; and (3) the signaling events controlling vasculogenesis, and ultimately arteriogenesis, of stem-cell grafts implanted into injured myocardium.
Elina Minami, MD (Medicine/Cardiology)
My work is linked closely with the mission of the Murry lab. Initially, my focus has been in the role of circulating progenitor cells in transplant arteriopathy, but it has now shifted in the area of small and large animal cardiovascular physiology.
Farid Moussavi-Harami (Medicine/Cardiology)
Our lab is interested in studying mechanisms of cardiomyopathies (disease of the heart muscle) using molecular and biomechanical approaches. In collaborations with other labs at UW, we are using gene therapy approaches to manipulate the force generation capacity of heart muscle to improve cardiac function. Overall goal of our research program is to have more targeted treatment for patients with cardiomyopathies.
Charles Murry, MD, PhD (Director, ISCRM; Pathology; Bioengineering; Medicine/Cardiology)
Developing cell-based therapies for cardiovascular disease, utilizing adult and human embryonic stem cells differentiated in vitro into cardiomyocytes, endothelial cells or their progenitors prior to delivery to diseased cardiac tissue.
Anna Naumova, PhD (Radiology)
I have a long-standing interest to scientific research, biomedical imaging and data analytics. The main focus of my research is advancing pre-clinical and clinical cardiovascular studies at the University of Washington by implementation of the state-of-the-art non-invasive imaging technology for assessment of heart physiology, pathophysiology, myocardial perfusion and tissue composition. Specifically, I am interested in heart regeneration with human cardiomyocytes and non-invasive imaging of transplanted cells. We are developing quantitative non-contrast MRI techniques for characterization of myocardial tissue composition. This would allow identification of the fibrotic areas and myocardial graft without need of the MRI contrast agents. Our imaging approach is suitable to clinical studies on patients.
Roberto Nicosia, MD, PhD (Pathology)
Angiogenesis plays an important role in the progression of cancer but also contributes to the revascularization of ischemic organs and tissue regeneration. Vascular stem cells actively participate in the formation of new blood vessels during embryonal development and in adults. The molecular mechanisms by which these cells promote angiogenesis have not been fully characterized. Using in vitro and in vivo models pioneered in our laboratory we are studying cellular and molecular mechanisms by which blood vessels regulate angiogenesis. Our studies indicate that vascular stem cells actively participate in this process and play an important role in the formation of the vessel wall. Our long term goal is to identify key mechanisms that turn angiogenesis “on” and “off”, and define the role of vascular stem cells in these processes.
Michael Portman, MD (Pediatrics)
My laboratory studies modulation of cardiac metabolism in order to improve cell viability and recovery after injury. We are hoping to expand our research to include the paracrine influence of stem cells on metabolism of regenerating heart tissue.
Bensheng Qiu, PhD (Radiology)
Dr. Qiu is focusing on developing various molecular MRI techniques for stem cell-gene therapy, such as molecular MRI of neural stem cell-based gene therapy for brain tumors, MRI of vascular gene therapy and interventional MRI, and translating these new techniques to clinical applications.
Buddy Ratner, PhD (Bioengineering)
Stem cells proliferate and differentiate in response to micromechanical cues, surface biological signals, orientational directives and chemical gradients. To control stem cell proliferation and differentiation, the Ratner lab brings 30 years experience in surface control of biology, polymer scaffold fabrication and controlled release of bioactive agents to address the challenges of directing stem cell differentiation and subsequent tissue formation.
Michael Regnier, PhD (Bioengineering)
The Regnier lab works in a highly collaborative environment to develop both cell replacement and gene therapies approaches to treat diseased and failing hearts and skeletal muscle. Cell replacement strategies include development and testing of tissue engineered constructs. Gene therapies are target and improve myofilament contractile protein function.
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.
Michael Sobel, MD (Surgery)
The Vascular Research Laboratories of the Department of Surgery at the VA Puget Sound HCS are led by Michael Sobel, Professor and Vice Chair, and Dr. Errol Wijelath, Research Asst. Professor. This group has been a leader in research on adult stem cells and endothelial progenitor cells, since Dr. Wijelath’s seminal publication proving that prosthetic vascular surfaces can become endothelialized from the hematogenous deposition of circulating adult stem cells. Currently the group has an NIH award supporting their work on developing novel molecules to enhance angiogenesis within vascular prostheses, and to promote differentiation of adult stem cells to the endothelial line.
April Stempien-Otero, MD (Medicine/Cardiology)
We are interested in the role of bone marrow derived cells in cardiac repair and regeneration. Our specific research lies in how bone marrow derived cells direct the accumulation of excess collagen (fibrosis) in the heart and how that process can be reversed to allow optimal endogenous or exogenous cardiac regeneration. Using a human model we are testing the hypothesis that direct injection of these bone marrow derived cells can alter fibrosis and improve blood vessel formation in hearts with end stage ischemic heart disease.
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.
Gale Tang, MD (Surgery)
The Tang lab focuses on peripheral vascular disease and new therapies for patients facing limb loss from arterial ischemia. I am interested in discovering cellular and molecular mechanisms of collateral artery development, or arteriogenesis. I hope to gain some understanding of the role of mesenchymal stem cells in this process, and how these cells can be modified to enhance collateral artery development to prevent limb loss.
Rong Tian, PhD (Anesthesiology & Pain Medicine, and 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.
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.
Zipora Yablanka-Reuveni, PhD (Biological Structure)
Skeletal muscle growth and regeneration depends mainly on myogenic stem cells that reside on the myofiber surface (i.e., satellite cells). Recent studies have suggested that uncharacterized stem cells residing in the vessel wall might be able to contribute myofiber nuclei as well. We investigate the function of both type of progenitors throughout the lifespan. Our research has the potential of contributing to the enhancement of the performance of resident (endogenous) myogenic stem cells in the aging muscle as well as for the development of cell-based therapies that can become useful to combat muscle lose following major muscle trauma and in myopathies.
Daniel Yang, MD (Medicine/Cardiology)
The Yang lab is interested in modeling genetic and acquired cardiomyopathies (disease of the heart muscle) with patient-specific and/or gene-edited human induced pluripotent stem cells. By studying the mechanisms that lead to heart disease in a human model, we hope to develop novel therapies that will better translate clinically for patients with heart disease. Ongoing projects are focused on cardiomyopathies due to inflammation, diabetes, and MYH7 mutations.
Xiaoming Yang, MD, PhD (Radiology)
Dr. Xiaoming Yang’s research team is focusing on fully applying the advances of modern imaging modalities to medicine, primarily developing new image-guided interventional techniques to monitor and guide stem cell and gene therapies, as well as immunotherapy of life-threatening diseases, such as atherosclerotic cardiovascular disease and different cancers.
Chun Yuan, PhD (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.