A postdoctoral position is available in the laboratory of Dr. Dana Graves at the University of Pennsylvania's School of Dental Medicine, Department of Periodontics, to investigate a newly identified mechanism through which diabetes impairs fracture healing and to develop a locally delivered therapeutic strategy to restore skeletal repair.
The project is supported by strong preliminary evidence demonstrating that lineage-specific deletion of FOXO1 in chondrocytes or osteoblasts reverses diabetes-impaired fracture healing. We have also found that disruption of primary cilia in these skeletal lineages reproduces defining features of defective repair in diabetes. Together, these findings identify and strongly support a previously unrecognized FOXO1-primary cilia signaling axis as an important regulator of skeletal regeneration under diabetic conditions.
The successful candidate will define how diabetes-induced FOXO1 activity alters ciliogenesis, cellular differentiation, and regenerative signaling in chondrocytes and osteoblasts. The studies will integrate conditional mouse models targeting FOXO1, IFT80, and combined FOXO1/IFT80 deletion with fracture-healing models of type 1 and type 2 diabetes to establish the cellular and molecular events that impair skeletal regeneration.
A major emphasis will be resolution of the fracture-healing microenvironment at spatial and single-cell resolution. Experimental approaches will include 10x Genomics Xenium spatial transcriptomics, single-cell RNA sequencing, computational analysis using R and Seurat, histology, immunofluorescence, semi-automated image analysis, and microcomputed tomography. These complementary methods will identify lineage-specific transcriptional programs, spatially organized signaling networks, and cellular interactions that distinguish effective from impaired skeletal repair and determine how these programs are altered by diabetes, FOXO1 activity, and loss of primary cilia.
The project also includes a translational component focused on a newly developed IGF-1 mimetic-containing nanofiber hydrogel designed for controlled local delivery at the fracture site. The candidate will examine its effects on inflammation and the sequential formation of immature mesenchymal tissue, cartilage, and bone, and determine whether the hydrogel restores cilia-dependent regenerative signaling, limits pathological FOXO1 activity, and improves structural and functional fracture healing in type 1 and type 2 diabetes. This work directly connects discovery of a previously unexplored regulatory pathway with preclinical evaluation of a locally delivered, mechanism-based therapy.
The fellow will be expected to take substantial intellectual ownership of the project, including development of experimental directions, leadership of spatial-transcriptomic and computational analyses, presentation of findings, and preparation of first-author manuscripts. The position provides multidisciplinary training at the interface of skeletal biology, diabetes, mouse genetics, spatial and single-cell genomics, computational biology, and translational biomaterials research. The fellow will receive direct scientific mentoring from Dr. Graves, regular project-based guidance, and opportunities to work with collaborators and shared-resource specialists across the University of Pennsylvania. Access to Penn core facilities and collaborative expertise will support spatial transcriptomics, single-cell genomics, imaging, histology, and quantitative analysis. Guided training in R, Seurat, and analysis of Xenium and single-cell datasets will be available to candidates who have strong experimental backgrounds but require additional computational experience. The research plan is designed to support intellectual independence, high-quality first-author publications, and development of a competitive platform for subsequent fellowship, faculty, or industry applications.
Applicants should hold a PhD, MD, DMD, DVM, or equivalent degree in skeletal biology, cell biology, molecular biology, bioengineering, diabetes biology, immunology, computational biology, or a related field.
Experience in one or more of the following areas is desirable: mouse genetics and disease models, bone or cartilage biology, fracture healing, spatial transcriptomics, single-cell RNA sequencing, computational analysis using R and Seurat, image analysis, molecular and cellular assays, histology, or microcomputed tomography. Candidates with strong experimental backgrounds who wish to develop expertise in osseous and regenerative biology, spatially resolved molecular analysis, and single-cell transcriptomics are encouraged to apply. Evidence of scientific rigor, clear communication, and the ability to work both independently and collaboratively will be important.
· Funding duration: The position if grant supported through 2028 and the PI has other grant support through 2031.
· Anticipated start date: Available immediately following interviews and feedback from references.
· Application materials: Please submit a curriculum vitae, a brief statement describing research experience and future interests, and the names and contact information of three references.
· Contact: Jen East jeneast@upenn.edu
The University of Pennsylvania is an equal opportunity employer. Candidates are considered for employment without regard to race, color, sex, sexual orientation, religion, creed, national origin (including shared ancestry or ethnic characteristics), citizenship status, age, disability, veteran status or any class protected under applicable federal, state, or local law.
