Regulation of osteoblast gene expression by microRNAs; Molecular mechanisms controlling bone remodeling.

Education

Degree	Institution	Major
BS	Roger Williams College	Chemistry
PhD	Dartmouth Medical School	Biochemistry

Post-Graduate Training

Training	Institution	Specialty
Postdoctoral	Dartmouth Medical School	Biochemistry (Constance Brinckerhoff, PhD)
Postdoctoral	Saint Francis Hospital & Medical Center	Postdoctoral Fellow, Bone Biology (Ernesto Canalis, MD)

Awards

Name of Award/Honor	Awarding Organization
Young Investigator Award	American Society for Bone and Mineral Research

l am very interested in mentoring and I am committed to the success of my graduate students. Recognizing that each student is different, I enjoy learning about my students and finding ways to help them build on their strengths and work on skills needing improvement.

Name & Description	Category	Role	Type	Scope	Start Year	End Year
Skeletal Biology Structure and Regeneration (SBSR) study section/NIH	Study Section	ad hoc committee member	External	National	2023
MD/PhD Admissions Committee	Advisory Committee	committee member	UConn Health	University	2023
Skeletal Biology Development and Disease (SBDD) Study Section	Study Section	ad hoc committee member	External	National	2022
Vidi-programme NWO/ZonMw / Dutch Research Council	Study Section	ad hoc committee member	External	International	2022
MD/PhD Executive Committee	Advisory Committee	committee member	UConn Health	University	2022
Member Conflict: Skeletal and Dental Biology and Tissue Engineering SEP/ NIH	Study Section	Committee Chair	External	National	2021
Graduate School Diversity, Equity and Inclusion Committee	Advisory Committee	committee member	UConn Health	University	2021
Skeletal Biology and Regeneration Recruitment Committee	Advisory Committee	Chair	UConn Health	University	2020	2022
Graduate Programs Committee	Advisory Committee	Chair	UConn Health	University	2020	2022
Education Council	Advisory Committee	committee member	UConn Health	University	2020	2022
Academic Advancement Committee	Advisory Committee	committee member	UConn Health	University	2020	2024
Graduate Faculty Council	Advisory Committee	member	UConn Health	University	2019	2020
Institutional Animal Care and Use Committee	Advisory Committee	member	UConn Health	Local	2018
Graduate Programs Committee	Advisory Committee	vice chair	UConn Health	Local	2018	2020
microCT Core Advisory Committee	Advisory Committee		UConn Health	University	2018
Skeletal Biology and Regeneration Program	Advisory Committee	director	UConn Health	Local	2016	2018
Skeletal Biology Structure and Regeneration (SBSR) Study Section	Study Section	Member	External	National	2015	2019
Society for Osteobiology	Professional/Scientific Organization	member	External	International	2015
Skeletal Biology and Regeneration Program	Advisory Committee	associate director	UConn Health	Local	2014	2016
Skeletal Biology and Regeneration Program Executive Committee	Advisory Committee	member	UConn Health	Local	2014	2020
Abstract Review Committee American Society for Bone and Mineral Research	Professional/Scientific Organization	member	External	International	2013	2013
Abstract Review Committee Member American Society for Bone and Mineral Research	Professional/Scientific Organization	member	External	International	2011	2011
Skeletal Craniofacial Oral Biology Graduate Program, Preliminary Exam Review Committee	Advisory Committee	member	UConn Health	University	2011	2011
Skeletal Craniofacial Oral Biology Graduate Program: Preliminary Exam Review Committee	Professional/Scientific Organization	Member	External	National	2011
Curriculum Policy Subcommittee	Advisory Committee	Vice Chair	UConn Health	University	2010
Endocrine Society	Professional/Scientific Organization	Member	External	National	2010
Curriculum Policy Subcommittee	Professional/Scientific Organization	Vice Chair	External	National	2010
Science Policy Committee American Society for Bone and Mineral Research	Professional/Scientific Organization	member	External	International	2008	2011
Molecular Core Advisory Committee	Advisory Committee	Member	UConn Health	University	2008
International Bone and Cancer Society	Professional/Scientific Organization	Member	External	International	2008
American Society for Bone and Mineral Research: Science Policy Committee	Professional/Scientific Organization	Member	External	National	2008	2011
Molecular Core Advisory Committee	Professional/Scientific Organization	Member	External	National	2008	2013
Faculty Search Committee, Center for Molecular Medicine	Professional/Scientific Organization	Member	External	National	2008	2009
Biomedical Sciences Graduate Admissions Committee	Professional/Scientific Organization	Application reviews, interviews	External	National	2007	2011
Abstract Review Committee Member American Society for Bone and Mineral Research	Professional/Scientific Organization	member	External	International	2004	2004
American Society for Bone and Mineral Research: Abstract Review Committee	Professional/Scientific Organization	Member	External	National	2004
Current Rheumatology Reviews	Editorial Board	Member	External	National	2004
Pilot & Feasibility Core UCHC Musculoskeletal Core Center Grant	Professional/Scientific Organization	Co-Director	External	University	2002	2004
American Society for Matrix Biology	Professional/Scientific Organization	Member	External	National	2000
Arthritis Research and Therapy	Professional/Scientific Journal	Member	External	National	1999	2009
American Society for Microbiology	Professional/Scientific Organization	Member	External	National	1995	2004
American Society for Bone and Mineral Research	Professional/Scientific Organization	member	External	International	1993

My laboratory is focused on understanding how microRNAs (miRNAs), which are a class of small non-coding RNAs, regulate gene expression in bone cells. Osteoblasts are the cells responsible for bone formation, and we are interested in determining the molecular mechanisms by which miRNAs control the differentiation and function of these cells. In the osteoblast lineage, we are currently studying the function and regulation of miR-433-3p. In collaboration with Dr. Sun-Kyeong Lee (Center on Aging) we are also investigating how the miR-29-3p family of miRNAs regulates the commitment and function of bone-resorbing osteoclasts.

We utilize in vitro studies to identify specific mRNAs and signaling pathways regulated by miRNAs. We follow up on these observations by examining the skeletal phenotype of mouse models in which the expression of either miR-29 or miR-433 is inhibited in a lineage-restricted manner. These mouse models are also useful for determining how miRNAs affect the response of the skeleton to intermittently administered parathyroid hormone (PTH), which is a bone anabolic therapy, or to exogenous glucocorticoids, which can cause bone loss.

In additional collaborative studies with Dr. Archana Sanjay (Department of Orthopedics), we are investigating how miRNAs regulate the process of fracture repair in young vs aged mice and in healthy vs diabetic mice.

Accepting Lab Rotation Students: Summer 2022, Fall 2022, and Spring 2023

Potential Lab Rotation Projects
1. Wnt signaling promotes commitment to the osteoblast lineage and is important for osteoblast function. miR-433 dampens Wnt signaling and we are interested in identifying components of the Wnt pathway that are targeted by miR-433.

2. A common progenitor gives rise to osteoclasts, macrophages and dendritic cells. Since miR-29 promotes osteoclast commitment in vitro, we are interested in determining whether progenitor cells from mice expressing a miR-29 inhibitor are more likely to differentiate towards the macrophage fate and whether RNAs important for macrophage commitment are targeted by miR-29.

3. Intermittent administration of PTH is a clinically relevant bone anabolic therapy. miR-433 targets Creb1, which is a transcription factor critical for signaling down stream of PTH receptor activation. We are interested in determining whether mice expressing a miR-433 inhibitor in bone are more responsive to intermittent PTH therapy.

Journal Articles

Book Chapters

Abstracts

Conference Papers

Notes

Reviews

Title or Abstract	Type	Sponsor/Event	Date/Year	Location
miRNAs in bone cells	Lecture		2021	University of Minnesota
miRNA regulation of gene expression in bone cells	Lecture	UConn RNA Salon	2019	UConn Storrs
Inhibition of miR-29 activity in the myeloid lineage by expression of a miR-29 tough decoy enhances trabecular bone volume in male mice	Poster	ASBMR	2019	Tampa, fl
Slit-ROBO Rho GTPase activating protein 2 (SRGAP2) in osteoclasts limits inflammatory osteoclastogenesis and inhibits expression of the coupling clastokine SLIT3.	Poster	ASBMR	2019	Tampa, fl
Meet the Professor: microRNAs and Bone	Lecture	American Society for Bone and Mineral Research	2018	Montreal, Canada
microRNA regulation of circadian rhythm in the osteoblastic lineage	Talk	Keystone Symposium: Small RNA Silencing: Little Guides, Big Biology	2016	Keystone, CO
Meet the Professor: microRNAs and Bone Homeostasis	Lecture	American Society for Bone and Mineral Research	2016	Atlanta, GA
miR-29 and Bone	Lecture	University of Uppsala	2014	Sweden
Polyadenylation, and MicroRNAs Targeting Insulin-like Growth Factor-1 in Osteoblasts	Poster	American Society for Bone and Mineral Research	2012	Minneapolis, Minnesota
miR-29 regulates osteoclastogenesis	Poster	American Society for Bone and Mineral Research	2012	Minneapolis, Minnesota
Role of miR-29 in bone	Lecture	Endocrine Society	2011	Boston,MA
MicroRNAs: No Small Role in Skeletal Regulation	Lecture	Endocrine Society	2011	Boston, Massachusetts
miR-29 Regulates Wnt Signaling in Human Osteoblasts Through A Positive Feedback Loop	Talk	American Society for Bone and Mineral Research	2010	Toronto, Canada
Bone Cartilage: Matrix Formation and Mineralization	Talk	American Society for Bone and Mineral Research	2010	Toronto, Canada
Osteonectin 3’ Untranslated Region Single Nucleotide Polymorphisms Differentially Regulate Gene Expression: microRNAs Target SNP Regions	Poster	American Society for Bone and Mineral Research	2010	Toronto, Canada
Analysis of the 3' Untranslated Region of the IGF-I Gene: Implications for mRNA Stability and Serum IGF-I Levels	Poster	American Society for Bone and Mineral Research	2009	Denver, Colorado
Interaction of Prostate Cancer Cells with Disorganized Bone Matrix Provides Resistance to Radiation-Induced Death In Vitro	Poster	American Society for Bone and Mineral Research	2009	Denver, Colorado
Association of Prostate Cancer Cells With Disorganized Bone Matrix Provides Resistance to Radiation-Induced Death In Vitro	Talk	International Meeting on Cancer Induced Bone Disease	2009	Arlington, Virgina
Function of Osteonectin in Bone, and its Post-transcriptional Regulation	Talk	American Society for Matrix Biology	2008	San Diego, CA
Regulation of Osteonectin/SPARC by MicroRNA-29	Talk	American Society for Bone and Mineral Research	2008	Montreal, Canada
Pediatric Nephrology Seminar Series	Talk	University of California	2008	Los Angeles, California
Special Interest Group – Bone Biology	Talk	American Society for Matrix Biology	2008	San Diego, California
Poorly Structured Bone Matrix, Reminiscent of an “Osteoblastic” Lesion Promotes an Aggressive Gene Expression Profile in Prostate Carcinoma Cells In vVtro	Talk	International Meeting on Cancer Induced Bone Disease	2008	Edinburgh, Scotland
Differential Regulation of Gene Expression by SNPs in the Osteonectin/SPARC 3’ Untranslated Region (UTR): A Mechanism for Modulation of Bone Mass	Poster	American Society for Bone and Mineral Research	2008	Montreal, Canada
Skeletal Biology Seminar Series	Talk	The Jackson Laboratories	2007	Bar Harbor, Maine
microRNAs and Bone	Lecture	American Society for Bone and Mineral Research	2006	Philadelphia, PA
Bone Rounds	Talk	Columbia University College of Physicians and Surgeons	2006	New York, New York
Trinity College Biology Department Seminar Series	Talk	Trinity College	2006	Hartford, Connecticut
Bone, Cartilage, Connective Tissue Matrix III	Talk	American Society for Bone and Mineral Research	2006	Philadelphia, Pennsylvania
“Meet the Professor” – MicroRNAs and Bone	Talk	American Society for Bone and Mineral Research	2006	Philadelphia, Pennsylvania
Osteonectin/SPARC is critical for anabolic response to PTH in the skeleton	Poster	American Society for Bone and Mineral Research	2006	Philadelphia, Pennsylvania
MicroRNA (miRNA) Binding Sites in the Osteonectin 3’ Untranslated Region (UTR) Regulate Expression	Talk	American Society for Bone and Mineral Research	2005	Nashville, Tennessee
Increased Notch 1 in Osteonectin-Null Osteoblasts: A Potential Mechanism for Aberrant Maturation	Poster	American Society for Bone and Mineral Research	2004	Seattle, Washington
Function and regulation of osteonectin in bone	Talk	Henry Ford Hospital	2003	Detroit, MI
State of the Art Lecture - Glucocorticoid Action	Talk	American Society for Bone and Mineral Research	2003	Minneapolis, Minnesota
Matricellular Proteins in Normal and Cancer Cell-Matrix Interactions	Talk	International Hermelin Brain Tumor Center Symposium	2003	Detroit, Michigan
Study of Osteonectin Gene Polymorphisms in Men With Idiopathic Osteoporosis	Poster	American Society for Bone and Mineral Research	2003	Minneapolis, Minnesota
Osteonectin in Bone	Panel Discussion	National Institutes of Health	2002	Bethesda, MD
Osteonectin Supports Osteoblast Maturation and Survival	Talk	American Society for Bone and Mineral Research	2002	San Antonio, Texas
Extracellular Matrix and Aging: Musculoskeletal System and Skin	Talk	National Institute on Aging Workshop	2002	Bethesda, Maryland
Osteonectin Supports Osteoblast Maturation and Survival	Poster	American Society for Bone and Mineral Research	2002	San Antonio, Texas
BMPs, TGF-beta, Other Growth Factors/Cytokines II	Talk	American Society for Bone and Mineral Research	2001	Phoenix, Arizona
The Osteonectin-Null Mutation Compromises Osteoblast Formation and Maturation	Poster	American Society for Bone and Mineral Research	2001	Toronto, Canada
Bone Cells – Osteoblasts II	Talk	American Society for Bone and Mineral Research	2000	Toronto, Canada
Aberrant In Vitro Differentiation of Marrow Stromal Cells from Osteonectin-Null Mice Correlates with Osteopenic Phenotype In Vivo	Poster	American Society for Bone and Mineral Research	2000	Toronto, Canada
Osteonectin-Null Mice Develop Severe Osteopenia	Talk	American Society for Bone and Mineral Research	1999
CAAT Enhancer Binding Proteins Mediate Down Regulation of Insulin-Like Growth Factor I by Cortisol in Osteoblasts	Poster	American Society for Bone and Mineral Research	1999
Fibroblast Growth Factor-2 Decreases Osteonectin RNA Stability and Regulates Novel RNA Binding Proteins Associated with its 3’-Untranslated Region	Poster	American Society for Bone and Mineral Research	1999
Fibroblast Growth Factor-2 (FGF-2) Modulates the Breast Cancer Associated Metalloproteinase, Stromelysin-3, in Osteoblasts	Poster	American Society for Bone and Mineral Research	1997
Basic Fibroblast Growth Factor (bFGF) Down-Regulates Osteonectin Expression in Osteoblasts by Transcriptional Mechanisms	Poster	American Society for Bone and Mineral Research	1996
Autocrine Suppression of Osteoblast Matrix Metalloproteinase I by Insulin-Like Growth Factor I	Talk	Endocrine Society	1995
Transcriptional Repression of Insulin-Like Growth Factor I by Transforming Growth Factor ß1 in Rat Osteoblast Cells	Talk	American Society for Bone and Mineral Research	1995
Transcriptional Repression of Matrix Metalloproteinase I by Insulin-Like Growth Factor I in Rat Osteoblast Cells	Talk	American Society for Bone and Mineral Research	1995
Cortisol Inhibits Insulin-Like Growth Factor-I (IGF-I) Expression in Osteoblasts by Transcriptional Mechanisms	Talk	American Society for Bone and Mineral Research	1994
Transcriptional Repression of the a1(I) Procollagen Gene by Cortisol in Cultured Rat Osteoblasts	Poster	Endocrine Society	1994
Cortisol Increases Interstitial Collagenase Expression in Osteoblasts by Post-Transcriptional Mechanisms	Poster	American Society for Bone and Mineral Research	1994
The Synthetic Retinoid (4-hydroxyphenyl)Retinamide Antagonizes TGFß Induced a1(I) Collagen mRNA	Poster	American College of Rheumatology	1990
Disparate Regulation of EGF-Induced Metalloproteinase Expression and Proliferation in Fibroblasts	Poster	American College of Rheumatology	1988