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TIAM1 dictates lineage commitment in skeletal and soft tissue pericytes

Award Number: K08DE031347
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 04/06/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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TIAM1 dictates lineage commitment in skeletal and soft tissue pericytes - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $166,058 )
2025	2025	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Oral Diseases and Disorders Research	000	4	4/1/2025	NON-COMPETING CONTINUATION	$166,058
														Subtotal = $166,058

Issue Date FY: 2024 ( Subtotal = $166,058 )
2024	2024	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Oral Diseases and Disorders Research	000	3	3/29/2024	NON-COMPETING CONTINUATION	$166,058
														Subtotal = $166,058

Issue Date FY: 2023 ( Subtotal = $166,058 )
2023	2023	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Oral Diseases and Disorders Research	000	2	3/13/2023	NON-COMPETING CONTINUATION	$166,058
														Subtotal = $166,058

Issue Date FY: 2022 ( Subtotal = $166,058 )
2022	2022	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Oral Diseases and Disorders Research	000	1	4/6/2022	NEW	$166,058
														Subtotal = $166,058

Grand Total All Awards = $664,232

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TIAM1 dictates lineage commitment in skeletal and soft tissue pericytes

Award Number: K08DE031347

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 04/06/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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