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.