Greg Holmes, PhD
- ASSISTANT PROFESSOR | Genetics and Genomic Sciences
Dr Greg Holmes received his PhD from The University of Queensland, Australia. In the laboratory of Dr 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, including the role of Sox2, in osteoblasts. While there, he developed a strong interest in craniofacial development, studying a mouse model of the Apert craniosynostosis syndrome. He joined the Jabs lab as an Instructor in 2011 to pursue further research into the molecular processes and tissue interactions underlying a variety of craniosynostosis syndromes.
BSc (Hons), Sydney University
PhD, University of Queensland
Craniosynostosis, the premature fusion of cranial sutures, is a relatively common childhood disease (seen in up to 1 in 2500 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 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 fibroblast growth factor receptor (Fgfr) mutations responsible for Apert, Crouzon, and Beare-Stevenson syndromes, 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.
Holmes G, Basilico C. Mesodermal expression of Fgfr2(S252W) is necessary and sufficient to induce craniosynostosis in a mouse model of Apert syndrome. Devl Biol 2012; 368(2): 283-293.
Wang Y, Zhou X, Oberoi K, Phelps R, Couwenhoven R, Sun M, Rezza A, Holmes G, Percival CJ, Friedenthal J, Krejci P, Richtsmeier JT, Huso DL, Rendl M, Jabs EW. p38 Inhibition ameliorates skin and skull abnormalities in Fgfr2 Beare-Stevenson mice. J Clin Invest 2012; 122(6): 2153-2164.
Deckelbaum RA, Holmes G, Zhao Z, Tong C, Basilico C, Loomis CA. Regulation of cranial morphogenesis and cell fate at the neural crest-mesoderm boundary by engrailed 1. Development 2012; 139(7): 1346-58.
Holmes G, Bromage TG, Basilico C. The Sox2 high mobility group transcription factor inhibits mature osteoblast function in transgenic mice. Bone 2011; 49(4): 653-61.
Holmes G, Rothschild G, Roy UB, Deng CX, Mansukhani A, Basilico C. Early onset of craniosynostosis in an Apert mouse model reveals critical features of this pathology. Dev Biol 2009; 328(2): 273-84.
Ambrosetti D, Holmes G, Mansukhani A, Basilico C. Fibroblast growth factor signaling uses multiple mechanisms to inhibit Wnt-induced transcription in osteoblasts. Mol Cell Biol 2008; 28(15): 4759-71.
Mansukhani A, Ambrosetti D, Holmes G, Cornivelli L, Basilico C. Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation. J Cell Biol 2005; 168(7): 1065-76.
Holmes G, Crooijmans R, Groenen M, Niswander L. ALC (adjacent to LMX1 in chick) is a novel dorsal limb mesenchyme marker. GEP 2003; 3(6): 735-41.
Holmes G, Niswander L. Expression of slit-2 and slit-3 during chick development. Dev Dyn 2001; 222(2): 301-7.