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Principal Investigator: Ginny Ching-Yun Hsu
Organization: OREGON HEALTH & SCIENCE UNIVERSITY
Fiscal Year: 2024
Award: $166,058
Funding agency: National Institute of Dental and Craniofacial Research
Project Summary/Abstract
Bone tissue has high intrinsic regenerative potential, yet deficits in mesenchymal precursor numbers, function,
or supportive tissues lead to non-healing bony defects – a significant clinical problem within and outside of the
dental sciences. Mixed stromal populations termed `mesenchymal stem cells' (MSCs) have clear therapeutic
benefit for skeletal tissue engineering, however recent clinical trials using MSC have demonstrated suboptimal
or inconsistent results. Our team has a long-standing interest in human pericytes for tissue engineering.
However, the tissue-specific attributes of human pericytes has also been increasingly recognized. To further
investigate the tissue-specific properties of human pericytes, we recently examined differences in FACS
purified human CD146+ pericytes from either skeletal or soft tissue sources. Results showed that CD146+
human pericytes have a tendency to replicate the microenvironment from which they are derived (either bone-
forming or fat-forming depending on tissue of origin). Leveraging transcriptomic analysis of FACS-purified cell
clones, we found that the activator of the Rho family of small GTPases TIAM1 plays a critical role in cellular
differentiation decisions in human pericytes. In the current K08 proposal, we will test the central hypothesis
that the osteogenic inhibitor TIAM1 maintains the adipose tissue identity of human pericytes, and that gene
deletion will drive bone anabolism among implanted human pericytes.
Dr. Ginny Ching-Yun Hsu, a postdoctoral fellow at the Johns Hopkins University School of Medicine, is an
orthodontist-scientist with a well-rounded training and a long-standing commitment to a research career. The
career development plan enables Dr. Hsu to gain additional expertise in three areas: 1) stem cell and bone
biology, 2) biostatistics and bioinformatics, and 3) translational research. Dr. Hsu will be supported by an
outstanding multidisciplinary mentoring team with expertise to cover all elements of her research and career
development. Dr. Aaron James, an expert in perivascular stem cells, skeletal tissue engineering and
translational research, is her primary mentor. Her co-mentor Dr. Bruno Péault is a pioneer in pericytes and
regenerative medicine. Her co-mentor Dr. Patrick Cahan and collaborator Ms. Linda Orzolek will provide
expertise in next-generation sequencing and bioinformatics analyses. Through a tailored curriculum of courses,
workshops, and the proposed research, Dr. Hsu will develop crucial skills to achieve her goal of becoming a
successful, independent clinician-scientist in the field of bone biology and tissue engineering. This research will
generate the basis for R01 proposals, focusing on pericyte-based cell therapy in arthritis, bone and cartilage
regeneration. Finally, this award will position Dr. Hsu to become a top-tier orthodontist-scientist and enable her
to make a significant contribution to the field of orthodontics.
Terms: <Adipocytes><Adipose Cell><Adipose tissue><Adventitial Cell><Anabolism><Anatomic Sites><Anatomic structures><Anatomy><Animals><Area><Arthritis><Assay><Award><Bio-Informatics><Bioassay><Bioinformatics><Biological Assay><Biology><Biometrics><Biometry><Biostatistics><Blood Vessels><Body Tissues><Bone Regeneration><Bone Tissue><CD146><CD146 protein><CRISPR approach><CRISPR based approach><CRISPR method><CRISPR methodology><CRISPR technique><CRISPR technology><CRISPR tools><CRISPR-CAS-9><CRISPR-based method><CRISPR-based technique><CRISPR-based technology><CRISPR-based tool><CRISPR/CAS approach><CRISPR/Cas method><CRISPR/Cas technology><CRISPR/Cas9><CRISPR/Cas9 technology><Calvaria><Cas nuclease technology><Cell Body><Cell Culture Techniques><Cell Differentiation><Cell Differentiation process><Cell Therapy><Cells><Cellular Matrix><Chicken Homolog of Gicerin><Clinical><Clinical Trials><Clone Cells><Clustered Regularly Interspaced Short Palindromic Repeats approach><Clustered Regularly Interspaced Short Palindromic Repeats method><Clustered Regularly Interspaced Short Palindromic Repeats methodology><Clustered Regularly Interspaced Short Palindromic Repeats technique><Clustered Regularly Interspaced Short Palindromic Repeats technology><Course Content><Cytoskeletal System><Cytoskeleton><Data><Defect><Dental><Development><Development Plans><Development and Research><Educational workshop><Elements><Family><Fat Cells><Fats><Fatty Tissue><Fatty acid glycerol esters><Future><Gene Deletion><Genes><Goals><Heterograft><Heterologous Transplantation><Histology><Human><Immunocompromised><Immunocompromised Host><Immunocompromised Patient><Immunohistochemistry><Immunohistochemistry Cell/Tissue><Immunohistochemistry Staining Method><Immunosuppressed Host><Implant><In Vitro><Investigators><Knock-out><Knockout><Lead><Lipocytes><MCAM><MCAM gene><MUC18><Mature Lipocyte><Mature fat cell><Melanoma Adhesion Molecule><Melanoma-Associated Glycoprotein MUC18><Mentors><Mesenchymal><Mesenchymal Progenitor Cell><Mesenchymal Stem Cells><Mesenchymal progenitor><Mesenchymal stromal/stem cells><Modeling><Modern Man><Molecular><Monomeric G-Proteins><Monomeric GTP-Binding Proteins><NGS Method><NGS system><Network Analysis><Organ><Orthodontics><Pathway Analysis><Pathway interactions><Pb element><Pericapillary Cell><Pericytes><Perivascular Cell><Physiologic Ossification><Physiological Ossification><Play><Population><Position><Positioning Attribute><Postdoc><Postdoctoral Fellow><Predisposition><Progenitor Cells><Property><R & D><R&D><Regenerative Medicine><Regulation><Reporter><Research><Research Associate><Research Personnel><Researchers><Role><Rouget Cells><Science><Scientist><Signal Pathway><Small G-Proteins><Small GTPases><Source><Susceptibility><T lymphoma invasion and metastasis><T-Lymphoma Invasion and Metastatis Inducing Protein 1><TIAM1><TIAM1 Protein><TIAM1 gene><Techniques><Testing><Therapeutic><Thinking><Tissue Engineering><Tissues><Training><Translational Research><Translational Science><Universities><Work><Workshop><Xenograft><Xenograft procedure><Xenotransplantation><adipose><arthritic><bioengineered tissue><biosynthesis><bone><bone cell><bone repair><calvarial><career><career development><cartilage regeneration><cell culture><cell cultures><cell mediated therapies><cell preparation><cell-based therapeutic><cell-based therapy><cellular differentiation><cellular therapeutic><cellular therapy><clinical relevance><clinically relevant><comparative><course curriculum><craniofacial><craniofacies><developmental><differential expression><differentially expressed><engineered tissue><gene deletion mutation><global gene expression><global transcription profile><glycoprotein MUC18><heavy metal Pb><heavy metal lead><human tissue><immunosuppressed patient><in vivo><inhibitor><interest><intracellular skeleton><knowledgebase><medical college><medical schools><melanoma cell adhesion molecule><mesenchymal stromal progenitor cells><mesenchymal-derived stem cells><mineralization><multidisciplinary><next gen sequencing><next generation sequencing><nextgen sequencing><normal ossification><novel><ossification><osteogenic><overexpress><overexpression><pathway><post-doc><post-doctoral><post-doctoral trainee><precursor cell><progenitor biology><progenitor cell biology><progenitor cell differentiation><progenitor cell fate><progenitor differentiation><progenitor fate><regenerate bone><regenerate new tissue><regenerate tissue><regenerating damaged tissue><regenerating tissue><regeneration potential><regenerative potential><research and development><research associates><rho><scRNA-seq><school of medicine><single cell RNA-seq><single cell RNAseq><single cell expression profiling><single cell transcriptomic profiling><single-cell RNA sequencing><skeletal><skeletal tissue><skills><small molecule><social role><soft tissue><stem and progenitor biology><stem and progenitor cell fate><stem and progenitor differentiation><stem cell biology><stem cell differentiation><stem cell fate><stem cells><thoughts><tissue regeneration><tissue regrowth><tissue renewal><tissue specific regeneration><tomography><transcriptional differences><transcriptome><transcriptomics><transdifferentiation><translation research><translational applications><translational investigation><vascular><white adipose tissue><xeno-transplant><xeno-transplantation><yellow adipose tissue>