Institute for Stem Cell & Regenerative Medicine

at the University of Washington

Regeneration

Christopher Allan, MD (Orthopaedics and Sports Medicine)
Digit regeneration in humans. Children regrow amputated digit tips, a unique instance of complex tissue regeneration in humans. The process is not well-understood at the cellular or molecular level. Our lab has developed and reported the first human fetal digit model of response to digit tip amputation. We have also provided the first evidence in humans that the regeneration-associated transcription repressor Msx-1 may be involved in this process. Insights like this may form the basis for future cellular, tissue-engineered, or gene therapies to stimulate regeneration after extremity injury or amputation.

Charlie Alpers, MD (Pathology)
Our research involves studies of kidney disease consequent to immune responses to foreign pathogens and as a consequence of diabetes.

Olivia Bermingham-McDonogh, PhD (Biological Structure; Adjunct Professor, Otolaryngology; Virginia Merrill Bloedel Hearing Research Center)
Her research involves development and regeneration of the mammalian cochlea. With 10% of the population experiencing significant hearing loss figuring out how to regenerate the hair cells is an important goal. It is not clear if the most promising approach will be to use exogenous stem cells or to attempt to stimulate inherent cells to divide and differentiate. This group is looking at all avenues.

Peter Chen, MD (Medicine)
My lab studies the mechanisms that govern airway repair after injury and how inappropriate repair proceeds to airway fibrosis.

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through tissue regeneration and the treatment of disease continues to grow, the majority of current strategies rely on outdated technology initially developed and optimized for starkly different applications.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.

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.

Clifford R. Hume, MD, PhD (Otolaryngology-HNS, Virginia Merrill Bloedel Hearing Research Center, UWMC)
The long-term goal of our research is to identify the molecular signals that regulate the formation of hair cells and their neuronal connections during development and use these signals to develop new strategies to treat human hearing loss. Major research projects focus on using transcription factor (bHLH, LIM-HD, HB) manipulation to regenerate damaged or missing cell types in the inner ear and repair of auditory neuron innervation through targeted growth factor expression. To extend these efforts in vivo, we devote a significant effort to optimizing gene delivery tools for use in the inner ear.

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.

Akio Kobayashi, PhD (Nephrology)
The primary interest of the Kobayashi laboratory is to understand the cellular and molecular regulatory mechanisms leading to the establishment of the mammalian kidney using the mouse as a model system. The laboratory also focuses on understanding the genes that are involved in reprogramming kidney cell types so that it can be ultimately possible to restore kidney function in patients with kidney disease, ultimately eliminating the need for dialysis or renal transplantation.

John K. McGuire, MD (Pediatrics)
My laboratory work is directed at understanding how epithelial responses to acute injury and infection regulate lung repair and resolution of inflammation. Our work has specifically focused on understanding the role of matrix metalloproteinases in controlling lung epithelial regeneration and lung epithelial cell interactions with inflammatory cells.

Randall T. Moon, PhD (Director, ISCRM; Howard Hughes Medical Institute, Pharmacology)
This lab works on controlling regeneration, and endogenous and transplanted stem and progenitor cells in vitro, by manipulating signal transduction pathways with small molecules. One example is increasing the success of hematopoietic stem cell transplant by activating the ß-catenin pathway, which is an approach moving into clinical trials. Another example is that the group has shown that enhancing the same pathway promotes regeneration of entire structures such as limbs in lower vertebrates. The laboratory is recognized as a world leader in signal transduction pathways involved in development and disease.

Elizabeth Oesterle (Otolaryngology-HNS, Virginia Merrill Bloedel Hearing Research Center, UWMC)
Our group works to restore hearing and balance problems by stimulating the regeneration of hair cells in adult inner ear tissues. We work to control the proliferation of endogenous stem/progenitor cells in inner ear sensory tissue by the addition of small molecules or by manipulating signaling pathways. One example is by adding members of the epidermal growth factor family, that we have discovered can stimulate limited production of new cells in mature inner ear tissues involved with balance (vestibular sensory epithelia).

David Parichy (Biology)
Our research program uses the zebrafish and related species to answer a variety of biological questions having both basic and translational relevance.

David W. Raible, PhD (Biological Structure)
We are interested in the development of the peripheral nervous system using zebrafish as a model. Current research focuses on two areas: sensory neurons derived from neural crest and the mechanosensory lateral line system.

Buddy Ratner (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 (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.

Jennifer Stone, PhD (Bloedel Hearing Research Center, UWMC)
This laboratory examines cellular and molecular mechanisms of hair cell regeneration in an avian model. The goal is to identify properties and regulation of sensory epithelial-derived stem cells/progenitors cells in birds, which undergo robust spontaneous hair cell regeneration. Ultimately, information gleaned from these studies will be used to determine why mammalian species fail to spontaneously regenerate hair cells and to develop regenerative therapies that can eventually be applied to treat deafness in humans.

Billie Swalla (Biology)
We are studying regeneration in marine invertebrates that are closely related to vertebrates. We have one research program on the regeneration of the central nervous system in hemichordates, a group of animals closely related to echinoderms. Some species of hemichordates can be completely cut in half, but then regenerate their heart, kidney and central nervous system (Rychel & Swalla, 2008, Develop. Dyn. 237: 3222-3232). The central nervous system rolls up from the ectoderm during regeneration, very similar to the way that it develops in chordates. We are investigating the origin and identity of the stem cells involved in regeneration in hemichordates. We have also shown that colonial ascidians undergo extensive regeneration, thorough activation of a piwi-positive stem cell population (Brown et al. 2009; JEZ:MDE 312B: 885-900). This is a process called Whole Body Regeneration (WBR) and is accomplished by the induction of vascular budding in the colony, after all of the individual adults have been removed. The budding is an interaction between the vascular epithelium and piwi-positive stem cells. We are studying these invertebrate model systems in an effort to better understand the cellular and molecular control of regeneration in vertebrates.

Stephen Tapscott (FHCRC)
We have two research programs in stem cell biology. We are studying the molecular mechanisms of specifying myogenic and neurogenic lineages with the long-term goal of generating myogenic and neurogenic stem cells. We are also studying muscle stem cell transplantation with the goal of reconstituting skeletal muscle in the recipient.

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.

 

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