Repair of calvarial bony defects remains challenging for craniofacial surgeons. Injury experiments on animal calvarial bones are widely used to study healing mechanisms and test tissue engineering approaches. Previously, we identified Gli1+ cells within the calvarial sutures as stem cells supporting calvarial bone turnover and injury repair. In this study, we tested the regenerative capacity of...

Endocrine resistance is a major challenge in the management of estrogen receptor (ER)-positive breast cancers. Although multiple mechanisms leading to endocrine resistance have been proposed, the poor outcome of patients developing resistance to endocrine therapy warrants additional studies. Here we show that noncanonical Hedgehog (Hh) signaling is an alternative growth promoting mechanism that...

Bone formation is a continuous process that begins during fetal development and persists throughout life as a remodeling process. In the event of injury, bones heal by generating new bone rather than scar tissue; thus, it can accurately be described as a regenerative process. To elucidate the extent to which fetal skeletal development and skeletal regeneration are similar, we performed a series...

IMPORTANCE Tumor resistance is an emerging problem for Smoothened (SMO) inhibitor-treated metastatic basal cell carcinoma (BCC). Arsenic trioxide and itraconazole antagonize the hedgehog (HH) pathway at sites distinct from those treated by SMO inhibitors. OBJECTIVE To determine whether administration of intravenous arsenic trioxide and oral itraconazole in patients with metastatic BCC is asso...

Abstract Medulloblastoma is the most common malignant brain tumor in children, accounting for 20-25% of all pediatric tumors. The current standard care includes both craniospinal and focal radiation therapy which lead to negative long term consequences population such as bone tissue hypoplasia, decreased neurocognitive functioning, well an increased risk secondary induced cancers. Thus, there a...

Albright hereditary osteodystrophy (AHO) is a disorder caused by GNAS heterozygous inactivation, and results in the spontaneous development of subcutaneous ossifications (SCOs) dermis tissue. We have generated an AHO mouse model through global Gnas inactivation (Gnas+/-) that phenocopies human develops SCOs consistently surround hair follicles (HF). Therefore, this study examined cellular molec...

The characterization of cells with tumour initiating potential is significant for advancing our understanding of cancer and improving therapy. Aggressive, triple-negative breast cancers (TNBCs) are enriched for tumour-initiating cells (TICs). We investigated that hypothesis that VEGF receptors expressed on TNBC cells mediate autocrine signalling that contributes to tumour initiation. We discove...

The vertebrate body is supported by a bony skeleton, which is largely formed by endochondral ossification. To ensure normal bone growth, differentiation of chondrocytes has to be tightly regulated. One of the major regulators of this process is the growth factor Indian hedgehog (Ihh). Endochondral ossification is impaired in Ihh mutant mice due to disturbed chondrocyte proliferation and differe...

Indian Hedgehog (HH) has been shown to be involved in osteoarthritis (OA) in articular joints, where there is evidence that Indian HH blockade could ameliorate OA. It seems to play a prominent role in development of the intervertebral disc (IVD) and in postnatal maintenance. There is little work on IHH in the IVD. Hence the aim of the current study was to investigate the role of Indian Hedgehog...