Greg Holmes, PhD Email Greg Holmes
- ASSISTANT PROFESSOR | Genetics and Genomic Sciences
Greg Holmes received his PhD from The University of Queensland, Australia. In the laboratory of Melissa Little, he characterized protein-DNA and protein-protein interactions of the Wilms’ tumor suppressor gene 1 (WT1) zinc-finger protein and the effect of Denys-Drash syndrome mutations on WT1 DNA binding. His postdoctoral training has been in the laboratories of Lee Niswander (Memorial Sloan-Kettering Cancer Center, NY) studying chick and mouse embryological limb development, and Claudio Basilico (NYU School of Medicine, NY) studying inhibitory interactions of the Fgf signaling pathway on the Wnt signaling pathway in osteoblasts. While there, he developed a strong interest in craniofacial development, studying a mouse model of the Apert craniosynostosis syndrome. He joined the laboratory of Ethylin Wang Jabs at Mount Sinai as an Instructor in 2011 to pursue further research into the molecular processes and tissue interactions underlying a variety of craniosynostosis syndromes. He is currently an Assistant Professor in the Department of Genetics and Genomic Sciences. Current projects are based on developing expression maps of murine craniofacial sutures during embryonic and postnatal development, through the integration of laser capture microdissection-derived bulk RNA-Seq and single cell RNA-Seq approaches. The goal is to understand suture development within the calvaria and face/palate by identifying and investigating the role of novel genes and cell subpopulations within sutures. This will enhance our understanding of disease mechanisms in craniofacial development and our ability to ameliorate or prevent these conditions.
Bone Biology, Cartilage Biology, Developmental Biology, Embryology, Molecular Biology, Morphogenesis, Skeletal Biology
BSc (Hons), Sydney University
PhD, University of Queensland
The vertebrate face is a complex structure. Integrated morphological development of the varied tissues and structures that comprise the face is critical for effective interaction with the environment, such as feeding and sensory perception, and the survival of the individual. Development of these tissues and structures often depend on the expression of shared genes, such as fibroblast growth factor receptors (Fgfrs), which can be mutated in human syndromes characterized by midface dysgenesis, often in conjunction with other deleterious effects on bodily growth, such as craniosynostosis (e.g., Apert and Crouzon syndromes) and dwarfism (e.g., Achondroplasia). We are using mouse models of specific human activating Fgfr mutations to investigate the structural, cellular, and molecular effects of these mutations in bone, cartilage, and epithelium that combine to cause midface dysgenesis.
Craniosynostosis, the premature fusion of cranial sutures, is a relatively common childhood disease (seen in up to 1 in 2,500 births), and can occur in isolation or as part of a syndrome affecting other organs in the afflicted individual. Where causative genetic mutations have been identified, mouse models are necessary to study the mechanisms of suture fusion and, in the case of syndromic craniosynostosis, the perturbed development of other tissues. We are using a variety of mouse models, particularly of Fgfr mutations responsible for Apert and Crouzon syndromes, and of the transcription factor Twist1 responsible for Saethre-Chotzen syndrome, to investigate the changes in molecular pathways and in tissue interactions underlying these syndromes, with a focus on cranial sutures, the palate, and the brain.
Craniofacial Suture Gene Expression and FaceBase
Knowing how sutures are formed and maintained is crucial to understanding craniofacial bone formation and the pathology of craniosynostosis, midface dysgenesis, and other craniofacial diseases. It is evident from gene expression patterns within sutures that signaling and regulatory pathways are organized within distinct cell subpopulations. Identifying both the full complement of gene expression and the cell subpopulation structure of sutures is vital to understanding the control of suture patency, osteogenesis and other suture functions such as providing stem cell niches and mechanical stability of the skull. In combination, single cell and bulk RNA-Seq applied to calvarial sutures provides this necessary information. As part of the FaceBase consortium (https://www.facebase.org/data/record/#1/isa:project/RID=1WW8) we are building a comprehensive RNA expression database comprised of 11 prenatal craniofacial sutures at key embryonic ages using laser capture microdissection-derived bulk RNA-Seq libraries from wild-type mice and craniosynostosis mouse models. These are complemented with single cell expression libraries for 4 calvarial sutures at key embryonic and postnatal ages from wild-type mice. Together with varied collaborators we are using differential gene expression analysis, gene co-expression network analysis, and a wide array of in vitro and in vivo experimental techniques to achieve a comprehensive description of suture biology and insights into suture and other craniofacial and bone diseases.
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Dr.Holmes did not report having any of the following types of financial relationships with industry during 2018 and/or 2019: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
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