Majesky Lab
In the Majesky Lab, we use molecular, biological and developmental genetic approaches to address fundamental questions in the development and differentiation of blood vessels. The vascular system consists of networks of blood and lymphatic vessels that interact with their target tissues in intricate and often surprising ways. One major research focus is on vascular stem and progenitor cells that reside in the adventitial layer of artery walls. Another major interest concerns molecular mechanisms that control formation and differentiation of coronary vessels.
Molecular mechanisms that control formation and differentiation of coronary vessels during heart development
Developmental fate mapping studies show that progenitor cells in the proepicardium (PE) give rise to coronary vessels. Formation of coronary vessels occurs by an epithelial to mesenchymal transition (EMT) of epicardial cells followed by vasculogenesis in the subepicardial space, assembly and remodeling of a primitive coronary plexus, and investment by pericytes and coronary smooth muscle cells (CoSMCs).
While these basic steps in coronary development are well established, the molecular mechanisms that control specification of PE cells to vascular progenitors, and the signaling pathways that couple epicardial cell EMT to transcriptional activation of CoSMC differentiation marker genes are still largely unknown. We are using transgenic and gene knockout approaches to examine the role of hedgehog and notch signaling pathways in coronary vessel development. Specifically, we are studying the molecular mechanisms by which epicardial cell-cell adhesion maintains epicardial-specific gene expression and represses CoSMC-specific gene transcription.
Vascular stem and progenitor cells that reside in the adventitial layer of artery wall
Our initial studies identified a novel sonic hedgehog (Shh) signaling domain restricted solely to the adventitia. Within this Shh signaling domain we found a population of stem cell antigen-1-positive (Sca1+) progenitor cells capable of differentiating to SMCs, pericytes, adipocytes, and osteogenic cells.
These current studies aim to understand the molecular genetic pathways that maintain these cells as self-renewing and undifferentiated progenitors within the arterial adventitia. We are also evaluating the role played by adventitial Sca1+ progenitor cells in angiogenesis of the vasa vasorum and in repair, remodeling and disease of the artery wall.
Partnership Opportunities
Mark W Majesky, PhD
Dr. Majesky is a professor of pediatrics at the University of Washington and director of the Myocardial Regeneration Initiative at Seattle Children's Research Institute. The goal of this groundbreaking initiative is to understand the molecular mechanisms involved in the embryonic development of the heart and vascular system in order to discover and develop applications for stem and progenitor cell-based therapies. Eventually, Majesky hopes to lead a multidisciplinary team of experts in genetics, bioengineering, developmental biology, pathology and clinical pediatrics in translating discoveries made in the laboratory into therapeutic opportunities in the areas of congenital heart defects and other cardiac abnormalities. Additionally, he leads the stem cell research efforts for Seattle Children's Heart Center, where his work will benefit the heart failure program.
An internationally recognized expert in the field of stem cell biology, Majesky began his research career at the University of Washington and has held faculty positions at both Baylor College of Medicine in Houston and the University of North Carolina at Chapel Hill. He served as president of the North American Vascular Biology Association from 2008 to 2009 and in 2009 received the American Heart Association Special Recognition Award in Vascular Biology.
-
Geoffrey Traeger
-
Abigail Tsai
David Bernard
Status in the lab: KO8 trainee
Current position: Medical Director of Clinical Pathology, Houston Methodist Hospital, Houston, TX
Chris Brewer
Status in the lab: Post-doc
Current position: Research Scientist, Sony Biotechnology, Bothell, WA
David Chang
Status in the lab: Grad student
Current position: Post-doc, California Institute of Technology, Pasadena, CA
Mikayla Chang
Status in the lab: Undergrad
Current position: Physician’s Assistant Program, Chatham University, Pittsburgh, PA
Matt DeAugustinis
Status in the lab: Undergrad
Current position: Physician, Mercy Medical Center, Redding, CA
Xiu Rong Dong, MD
Colin Enderlein
Status in the lab: Undergrad
Current position: Project Leader, DeciBio Consulting LLC, Los Angeles, CA
Benjamin Eng
Status in the lab: Undergrad
Current position: Electrical Engineering, University of Washington, Seattle, WA
Stephen Foster
Status in the lab: Post-doc
Current position: Clinical Pathologist, Lab Physicians Associates, Dallas, TX
Gavin Ford
Status in the lab: Undergrad
Current position: Physician, Walter Reed National Military Center, Bethesda, MD
Ginny (Hoglund) Schultz
Status in the lab: Grad student
Current position: Histotechnologist, Ben Towne Cancer Center, Seattle Children’s Research Institute, Seattle, WA
Robert Kao
Status in the lab: Post-doc
Current position: Associate Professor, Natural Science, Heritage University, Toppenish, WA
Po-Tsan Ku
Status in the lab: Post-doc
Current position: Career Development Specialist, University of Texas, Austin, TX
Tom Landerholm
Status in the lab: Grad student
Current position: Professor, Biological Sciences, California State University, Sacramento
Augustine Lee
Status in the lab: Undergrad
Current position: Colorectal Surgeon, Medical City Healthcare, Ft. Worth, TX
Mira Levensen
Status in the lab: Undergrad
Current position: Medical School, Trinity College, Dublin, Ireland
Jun Lu
Status in the lab: Grad student
Current position: Booth School of Business, MBA Program, University of Chicago
Colin Maguire
Status in the lab: Grad student
Current position: Director, Cellular Translational Research Core, University of Utah
Kenichi Nomoto
Status in the lab: Post-doc
Current position: President, Oncology Product Creation Unit, Eisai Inc., Cambridge, MA
Jana Pindur
Status in the lab: Post-doc
Current position: Physician-Pathologist, Kaiser Permanente, Anaheim, CA
Britta (Perkins) Braaten
Status in the lab: Undergrad
Current position: Science & Math Teacher, North Carolina
Jenna (Passman) Regan
Status in the lab: Grad student
Current position: Assistant Professor, Health Science Education (Genetics), University of Illinois-Peoria
Laurel Rodgers, PhD
Status in the lab: Post-doc
Current position: Associate Professor, Biology, Shenandoah University, Winchester, VA
Shivraj Sohur
Status in the lab: Undergrad
Current position: Physician, Neurology, Massachusetts General Hospital, Boston, MA
Liz (Stanley) Shepherd
Status in the lab: Undergrad
Current position: Co-Founder, Novome Biotechnologies, South San Francisco, CA
Chang Su
Status in the lab: Post-doc
Current position: Associate Professor, Pharmacology & Neuroscience, University of North Texas, Ft. Worth, TX
Elizabeth Stanley
Graham Strub
Status in the lab: Post-doc
Current position: Assistant Professor, Otolaryngology, Arkansas Children’s Hospital, University of Arkansas, Little Rock, AR
Stavros Topouzis, PhD
Status in the lab: Post-doc
Current position: Associate Professor, Pharmacology & Toxicology, University of Patras, Patras, Greece
Jun Wei
Status in the lab: Grad student
Current position: Staff Scientist, Genetics Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD
San-Pin Wu
Status in the lab: Grad student
Current position: Staff Scientist, Reproductive & Developmental Biology Laboratory, NIEHS, NIH, Durham, NC
Qingping Wu, PhD
Kevin Yu, PhD