Peter F. Maye, Ph.D.Associate Professor, Reconstructive Sciences
Skeletal Development & Regeneration
Research in my lab has a great interest in understanding signaling mechanisms that influence the fate of skeletal progenitors during the development, maintenance, and regeneration of bone tissues. Ongoing work includes the use of mouse and human embryonic stem cells and induced pluripotent stem (iPS) cells and learning how to direct their differentiation into cells of the axial skeleton. We also investigate adult bone marrow mesenchymal stem cells (MSCs) and the signaling pathways that influence their fate and function.
Rare Skeletal Diseases
Research in my lab is also interested in different skeletal dysplasia that impact bone tissues. We have become very interested in a rare craniofacial disorder known as cherubism. Currently, this work is focused on understanding how the Transforming Growth Factor Beta signaling pathway contributes to the pathology of this disease.
Differentiation of embyronic stem cells and iPS cells into mature skeletal cell types
Understanding how to generate skeletal progenitors from pluripotent stem cells has potentially great value for understanding the molecular basis of skeletal diseases and for the field of regenerative medicine. Currently, the field is beginning to make real progress in understanding how to differentiate pluripotent stem cells in a very defined way into skeletal progenitors. However, the cell types generated in vitro are very heterogeneous and their functional validation remains poorly tested. With this in mind, part of our strategy involves genetically engineering mouse and human ES and iPS cells with fluorescent reporters that enable us to visualize and study the biology of distinct skeletal progenitors generated in vitro. In conjunction with different reporter stem cell lines, we are investigating how different signaling pathways influence the differentiation of pluripotent stem cells into paraxial mesoderm. We are very interested in how to make paraxial mesoderm cells because they have the potential to give rise to wide breadth of mature skeletal cell types including, osteoblast, chondrocyte, tenocyte, myoblast, and dermal fibroblast.
Cherubism and Transforming Growth Factor (TGF) Beta Signaling
Cherubism is a rare autosomal dominant craniofacial disorder affecting pre-pubertal children, which is characterized by multilocular lesions in the mandible and/or maxilla consisting of numerous giant osteoclasts and extensive fibrous-osseous tissue hyperplasia. Currently, there is no accepted treatment for this disease. Based on certain characteristics of the cherubism phenotype, we suspected that increased TGFβ signaling may have a key role in the presentation of this disease and have used a mouse model of Cherubism to investigate this possibility. Our ongoing studies are very encouraging and provide evidence that reducing TGFbeta signaling may be an effective therapuetic approach to treat patients.
Accepting Lab Rotation Students: Fall 2022 and Spring 2023
Predicting the targets of IRF8 and NFATc1 during osteoclast differentiation using the machine learning method framework cTAP.
BMC genomics 2022 Jan;23(1):14
A transgenic bacterial artificial chromosome approach to identify regulatory regions that direct Amhr2 and Osterix expression in Müllerian duct mesenchyme.
Frontiers in cell and developmental biology 2022 Jan;101006087
Parental Origin of Gsα Inactivation Differentially Affects Bone Remodeling in a Mouse Model of Albright Hereditary Osteodystrophy.
JBMR plus 2022 Jan;6(1):e10570
Skeletal Screening IMPC/KOMP using μCT and Computer Automated Cryohistology: Application to the Efna4 KO mouse line.
Bone 2020 Oct;115688
Investigating global gene expression changes in a murine model of cherubism.
Bone 2020 Mar;135115315
Expression of BSP-GFPtpz Transgene during Osteogenesis and Reparative Dentinogenesis.
Journal of dental research 2020 Jan;99(1):89-97
Engraftment of skeletal progenitor cells by bone directed transplantation improves osteogenesis imperfecta murine bone phenotype.
Stem cells (Dayton, Ohio) 2019 Dec;
Derivation of notochordal cells from human embryonic stem cells reveals unique regulatory networks by single cell-transcriptomics.
Journal of cellular physiology 2019 Dec;
Generation and characterization of DSPP-Cerulean/DMP1-Cherry reporter mice.
Genesis (New York, N.Y. : 2000) 2019 Jul;e23324
Inverse agonism of retinoic acid receptors directs epiblast cells into the paraxial mesoderm lineage.
Stem cell research 2018 May;3085-95
Rescue of a cherubism bone marrow stromal culture phenotype by reducing TGFβ signaling.
Bone 2018 Mar;11128-35
Cell origin, volume and arrangement are drivers of articular cartilage formation, morphogenesis and response to injury in mouse limbs.
Developmental biology 2017 Apr;42656-68
FGF Signaling Prevents the Terminal Differentiation of Odontoblasts.
Journal of dental research 2017 Feb;96663-670
Loss of Cbl-PI3K interaction modulates the periosteal response to fracture by enhancing osteogenic commitment and differentiation.
Bone 2016 Nov;95124-135
Murine supraspinatus tendon injury model to identify the cellular origins of rotator cuff healing.
Connective tissue research 2016 May;57507-515
Evaluation of the donor cell contribution in rhBMP-2 mediated bone formation with chitosan thermogels using fluorescent protein reporter mice.
Journal of biomedical materials research. Part A 2015 Dec;104928-41
Enhanced Dentinogenesis of Pulp Progenitors by Early Exposure to FGF2.
Journal of dental research 2015 Aug;94(11):1582-90
Derivation of chondrocyte and osteoblast reporter mouse embryonic stem cell lines.
Genesis (New York, N.Y. : 2000) 2015 Mar;53(3-4):294-8
Connective Tissue Growth Factor reporter mice label a subpopulation of mesenchymal progenitor cells that reside in the trabecular bone region.
Bone 2015 Feb;7176-88
Evaluation of rhBMP-2 and bone marrow derived stromal cell mediated bone regeneration using transgenic fluorescent protein reporter mice.
Journal of biomedical materials research. Part A 2014 Dec;102(12):4568-80
Mouse limb skeletal growth and synovial joint development are coordinately enhanced by Kartogenin.
Developmental biology 2014 Sep;395(2):255-67
Enzymatically cross-linked bovine lactoferrin as injectable hydrogel for cell delivery.
Tissue engineering. Part A 2014 May;20(21-22):2830-9
Generation and characterization of Osterix-Cherry reporter mice.
Genesis (New York, N.Y. : 2000) 2013 Apr;51(4):246-58
Osterix-cre labeled progenitor cells contribute to the formation and maintenance of the bone marrow stroma.
PloS one 2013 Jan;8(8):e71318
In vivo fate mapping identifies mesenchymal progenitor cells.
Stem cells (Dayton, Ohio) 2012 Feb;30(2):187-96
Generation and characterization of Col10a1-mcherry reporter mice.
Genesis (New York, N.Y. : 2000) 2011 May;49(5):410-8
Engineering BAC reporter gene constructs for mouse transgenesis.
Methods in molecular biology (Clifton, N.J.) 2011 Jan;693163-79
A nondestructive method for evaluating in vitro osteoblast differentiation on biomaterials using osteoblast-specific fluorescence.
Tissue engineering. Part C, Methods 2010 Dec;16(6):1357-66
Isolation of murine bone marrow derived mesenchymal stem cells using Twist2 Cre transgenic mice.
Bone 2010 Nov;47(5):916-25
A BAC-bacterial recombination method to generate physically linked multiple gene reporter DNA constructs.
BMC biotechnology 2009 Jan;920
The 3.6 kb DNA fragment from the rat Col1a1 gene promoter drives the expression of genes in both osteoblast and osteoclast lineage cells.
Bone 2006 Dec;39(6):1302-12
The Wnt co-receptor LRP5 is essential for skeletal mechanotransduction but not for the anabolic bone response to parathyroid hormone treatment.
The Journal of biological chemistry 2006 Aug;281(33):23698-711
Examination of mineralized nodule formation in living osteoblastic cultures using fluorescent dyes.
Biotechnology progress 2006 Jan;22(6):1697-701
Dkk2 has a role in terminal osteoblast differentiation and mineralized matrix formation.
Nature genetics 2005 Sep;37(9):945-52
Expression profile of osteoblast lineage at defined stages of differentiation.
The Journal of biological chemistry 2005 Jul;280(26):24618-26
Histological analysis of GFP expression in murine bone.
The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 2005 May;53(5):593-602
Multiple mechanisms for Wnt11-mediated repression of the canonical Wnt signaling pathway.
The Journal of biological chemistry 2004 Jun;279(23):24659-65
Hedgehog signaling is required for the differentiation of ES cells into neurectoderm.
Developmental biology 2004 Jan;265(1):276-90
Regulation of Gli1 transcriptional activity in the nucleus by Dyrk1.
The Journal of biological chemistry 2002 Sep;277(38):35156-61
|Title or Abstract||Type||Sponsor/Event||Date/Year||Location|
|Murine Animal Models to Interrogate the Function and Commitment of Skeletal Progenitors||Talk||New England Musculoskeletal Institute Research Day||2016||Farmington, CT|
|Understanding the Coordinated Development of Bone Tissue and the Bone Marrow||Lecture||University of Hartford||2016||West Hartford, CT|
|Cherubism and Transforming Growth Factor Beta Signaling||Talk||Dental Dean's Lecture Series||2016||Farmington, CT|
|Development of Genetic Models to Study Cartilage Biology||Talk||New England Musculoskeletal Institute Research Day||2014||Farmington, CT|
|Genetic Approaches to Study Adult Bone Marrow Skeletal Progenitors||Talk||Connecticut Science Festival Stem Cell Panelist||2014||Farmington, CT|
|Mouse Transgenesis: Approaches to Genetically Engineer Mice||Lecture||University of Hartford||2014||West Hartford, CT|
|Fate Mapping with Osterix Cre Mice Reveals the Origin and Contribution of Bone Marrow Mesenchymal Stem Cells||Talk||American Society for Bone and Mineral Research Meeting||2012||Minneapolis, MN|
|Differentiating Embryonic Stem Cells Down the Axial Skeletal Lineage||Lecture||Central Connecticut State University||2012||New Britain, CT|
|Differentiating Embryonic Stem Cells Down the Axial Skeletal Lineage||Talk||Stem Cells and Regenerative Biology Symposium, UCONN Health||2011||Farmington, CT|
|New Fluorescent Protein Reporter Animal Models to Study Skeletal Biology||Poster||ASBMR||2010||Toronto, Canada|
|The Application of Transgenic Reporter Mice to Study Skeletal Cell Types||Talk||Dental Dean's Seminar Series||2010||Farmington, CT|
|Characterizing the Osteogenic Potential of Mesenchymal Stem Cells and Their Immediate Cellular Derivatives||Poster||American Society for Bone and Mineral Research||2009||Denver, CO|
|The Next Generation of Fluorescent Protein Reporter Animal Models to Mark Skeletal Cell Types||Talk||Regenerative Engineering Workshop||2009||Farmington, CT|
|Dermo1 Lineage Tracing Identifies Early Osteoprogenitor Cells in Adult Murine Bone Marrow Mesenchymal Stem Cell Cultures||Poster||ASBMR||2008||Montreal, Canada|
|Engineering Mice with Multiple BAC Fluorescent Protein Reporter Gene Elements||Poster||American Society for Bone and Mineral Research||2008||Montreal, Canada|
|Engineering Mice with Multiple Reporter Gene Elements||Talk||New England Musculoskeletal Institute Research Day||2008||Farmington, CT|
|Engineering Mice with Multiple BAC Fluorescent Protein Reporter Gene Elements||Poster||Endocrine Society /Endocrine Fellows Forum||2007||Honolulu, Hawaii|
|A Bacterial Recombination Strategy to Generate Linked Multiple Gene Reporter Constructs||Poster||IADR||2007||New Orleans, LA|
|A Bacterial Recombination Strategy to Link Multiple Gene Reporter Constructs||Poster||StemConn||2007||Hartford, CT|
|Characterization of LRP5 Mutant Osteoblast Cultures using Collagen 1a1 GFP Reporter Mice||Poster||ASBMR||2006||Philadelphia, PA|
|Haploinsufficiency of Beta-Catenin Results in Reduced Bone Mass||Poster||ASBMR||2005||Nashville, Tennessee|