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The Role of Mustn1 in Cartilage Biology

Award Number: R15HD092931
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2017
PERIOD OF PERFORMANCE END DATE: 07/31/2021

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The Role of Mustn1 in Cartilage Biology - Program Director/Principal Investigator (Last, First, Middle): Hadjiargyrou, Michael PROJECT SUMMARY (See instructions): Cartilage is the initial tissue of the skeleton that forms during embryonic development and participates in endochondral ossification of bones during growth and fracture repair. Chondrogenesis and subsequent bone formation is a complex process that is guided by cellular events ultimately governed by genetic networks. Identifying key regulatory genes of chondrogenesis is essential in enhancing our understanding, not only of cartilage formation, but also of skeletal pathologies and repair. The main objective of this proposal is to establish a functional relationship between Mustn1 (discovered in my laboratory) and chondrogenesis by generating and characterizing Mustn1 conditional knockout (KO) mice. Previously, we showed Mustn1 to be robustly expressed in the developing skeletal system; to display differential temporal and spatial expression in proliferating chondrocytes of articular cartilage and cartilaginous fracture callus, necessary for chondrogenic proliferation and differentiation in vitro; and, when silenced, to downregulate cartilage-related genes, thus leading to severe cartilage deficits during development in vivo. We plan to extend these findings and test the hypothesis that Mustn1 is a key regulator in chondrocytes and is required for cartilage formation during embryonic development and fracture repair. To address this hypothesis, we will generate Mustn1 conditional (in cartilage) KO mice and assess its role during skeletal development and growth (Aim 1) and fracture repair (Aim 2). By examining the consequences of Mustn1 deletion in chondrocytes, its functional contribution to chondrogenesis and overall skeletal development and repair will be clearly deciphered. We are hopeful that in the future, this will enable us to address a major challenge in orthopaedic medicine, that is, cartilage regeneration necessary to repair joint surface defects arising from trauma or arthritis, as well as impaired fracture repair (i.e. delayed and nonunions). Moreover, as Mustn1 does not belong to any known class of proteins, its investigation may lead to the elucidation of a new and uncharacterized protein family and/or regulatory pathways vital to chondrogenesis. Lastly, these transgenic mice will be available and serve as useful experimental tools for many investigators working on various cellular and molecular aspects of cartilage biology. PROJECT/PERFORMANCE SITE(S) (if additional space is needed, use Project/Performance Site Format Page) New York Institute of Technology (NYIT) Stony Brook University (SBU) PHS 398 (Rev. 03/16 Approved Through 10/31/2018) OMB No. 0925-0001 Page 2 Form Page 2


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: 2022 ( Subtotal = -$18,551 )
2022	2017	NEW YORK INSTITUTE OF TECHNOLOGY	NORTHERN BLVD	OLD WESTBURY	NY	11568	NASSAU	USA	Child Health and Human Development Extramural Research	000	1	2/1/2022	NEW	-$18,551
														Subtotal = -$18,551

Issue Date FY: 2017 ( Subtotal = $442,262 )
2017	2017	NEW YORK INSTITUTE OF TECHNOLOGY INC	NORTHERN BLVD	OLD WESTBURY	NY	11568	NASSAU	USA	Child Health and Human Development Extramural Research	000	1	7/20/2017	NEW	$442,262
														Subtotal = $442,262

Grand Total All Awards = $423,711

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The Role of Mustn1 in Cartilage Biology

Award Number: R15HD092931

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/01/2017

PERIOD OF PERFORMANCE END DATE: 07/31/2021

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