Alessandro Bertero, PhD (Pathology)
Our mission is dual: (1) to elucidate the gene regulatory mechanisms underpinning cardiac development and disease; and (2) to leverage this knowledge to develop gene, cell, and tissue engineering strategies for cardiac therapeutics. The current focus of genomic studies is the role of three-dimensional chromatin organization in dilated cardiomyopathy and congenital heart disease. Engineering efforts are now concentrated on the generation of genetically modified human pluripotent stem cell-derived cardiomyocytes to improve to improve production scalability, safety, and efficacy for cardiac regenerative medicine applications.
Christine Disteche, PhD (Pathology)
Research in my lab focuses on the regulation of the mammalian X chromosome.
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.
Marshall Horwitz, MD, PhD (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.
David Kimelman, PhD (Biochemistry)
This lab dissects the formation of mesodermal progenitor cells in zebrafish as a model organism, focusing on how these cells form the trunk and tail.
Ronald Kwon (Orthopaedics and Sports Medicine)
Our lab is focused on skeletal disease and regeneration. We are understanding the genetic basis of osteoporosis, and identifying new therapeutic targets to combat this massive health burden. We are also understanding why certain organisms such as fish are able to regenerate bony appendages following amputation, and how to mount this response in the digits and limbs of mammals.
The Musculoskeletal Systems Biology Lab comprises engineers, basic scientists, and clinicians. Our focus is on taking bold, innovative approaches to reverse aging-induced bone fragility, and to help realize human regenerative potential.”
Paul Lampe (Fred Hutch)
Our interests in stem cell biology and regenerative medicine mainly revolve around the protein I have spent the last 25-plus years studying, connexin43 (Cx43). Cx43 is the primary protein in gap junctions, a subcellular structure that couples intercellular communication to a cytoplasmic scaffold that coordinates cellular responses to different stimuli including epidermal wounding cardiovascular ischemia and tumorigenesis. Gap junctions are critical at many developmental stages and in response to injury. Specifically, we are interested in understanding the role that Cx43 regulation plays in stem cells and tissue reorganization during epidermal wound repair. Cx43 plays a key role in the initiation of migration and up regulation of proliferation needed to fill in the wound bed – so called re-epithelialization. We study this process using a transgenic mice and human studies. Gap junctions play a key role in regulating sodium and potassium flux between cardiomyocytes and are downregulated during cardiac disease; we have a long-standing collaboration with Mike Laflamme to determine whether modulation of gap junctions can achieve better engraftment of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) post myocardial infarction. We have also studied the role of Cx43 in differentiation of stem cells into definitive endoderm during pancreas development in collaboration in Vincenzino Cirulli. We encouraged and assisted the Allen Institute in the creation of hiPSCs that express one copy of Cx43-GFP that we hope will be useful in further studying the role of Cx43 in stem cell differentiation and cell fate.
Ghayda Mirzaa, MD (Pediatrics)
The broad goal of our research is to understand the causes, mechanisms and outcomes of human developmental brain disorders, including brain growth abnormalities (megalencephaly, microcephaly), malformations of cortical development and associated co-morbidities including autism, epilepsy and intellectual disability. Our work has led to gene discovery for several disorders associated with brain growth dysregulation including megalencephaly (e.g. PIK3CA, PIK3R2, AKT3, MTOR, CCND2) and microcephaly (e.g. STAMBP, CENPE, KIF11, CDC42), among several others (Mirzaa et al., Neuropediatrics 2004; Mirzaa et al., AJMG 2012; McDonnell et al., Nature Genetics 2013; Mirzaa et al., Pediatric Neurology 2013; Mirzaa et al., Human Genetics 2014; Martinelli et al., American Journal of Human Genetics 2018). Our work on the PI3K-AKT-MTOR related brain overgrowth disorders has led to the identification of several genes within this pathway that cause brain growth dysregulation and focal cortical dysplasia, with important therapeutic implications using PI3K-AKT-MTOR pathway inhibitors (Rivière et al., Nature Genetics 2012; Mirzaa et al., Nature Genetics 2014; Jansen et al., Brain 2015; Mirzaa et al., Lancet Neurology, 2015; Mirzaa et al., JAMA Neurology, 2016).
Our lab is focused on identifying the molecular and cellular mechanisms of developmental brain disorders and translating these genomic discoveries to molecularly-guided therapies using high throughput genomic, transcriptomic, and proteomic methods in relevant human tissues, combined with functional validation of genetic variants using human reprogramming and genome editing via CRISPR-Cas9 methods. Our lab houses the first human stem cell tissue culture facility at the Seattle Children’s Research Institute (SCRI) solely dedicated to generating human induced Pluripotent Stem Cells (iPSCs), Neural Progenitor cells (NPCs), cortical neurons and cerebral organoids to model genetic variants that are of high relevance to neurodevelopmental disorders, and to be used as a platform for future pre-clinical high throughput drug screening.
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.
Jason G. Smith, PhD (Microbiology)
Our laboratory cultures enteroid “mini guts” from adult intestinal epithelial stem cells to study the genetics of inflammatory bowel disease (IBD), Paneth cell development and function, and host pathogen interactions in the gut.
Valeri Vasioukhin (Fred Hutch)
Our laboratory studies the mechanisms and significance of cell polarity and cell adhesion in normal mammalian development and cancer.
Li Xin (Urology)
We are interested in using the prostate as a tissue model to study the molecular and cellular mechanisms that regulate development, tissue homeostasis and carcinogenesis. Currently, there are two major research focuses in the lab. The first research focus is to characterize the prostate epithelial lineage hierarchy. We seek to investigate how individual prostate epithelial lineages are maintained in adults by prostate stem cells or progenitors, and to identify master regulators that control adult prostate homeostasis. Cells of origin for tumor can dictate the clinical behaviors of the resulting diseases. Investigating the normal prostate lineage hierarchy serves as a prerequisite to understanding the cells of origin for prostate cancer, which will ultimately help understand the cellular basis for the aggressive prostate cancer. The second focus of the lab is to investigate the molecular mechanisms underlying the initiation and progression of the prostate related diseases including prostate cancer and benign prostatic hyperplasia. We are interested in determining the function of genetic changes or altered signaling that are associated with these diseases using genetically engineered mouse models. This work will inspire novel prognostic markers and therapeutic targets for these diseases.