Research Areas
The Goudy Regenerative Research Lab is focused on understanding the basic biologic mechanisms that control facial bone and soft tissue regeneration. Dr. Goudy’s clinical job involves repair of craniofacial malformations including cleft lip, cleft palate and Pierre Robin sequence, and he also participates in head and neck tumor resection and reconstruction. In both scenarios, children need cutting edge therapies to improve wound healing, reduce operative complications, and develop novel therapies to restore function and reduce morbidity.
Our lab is focused on modeling bone and soft tissue loss in the craniofacial skeleton and we have developed models that allow us to study this in depth. Using these models, the Goudy lab collaborates with multiple labs at both Emory and Georgia Tech to further develop regenerative approaches to craniofacial bone formation and soft tissue repair following injury. Specifically, these regenerative therapies include: delivery of Jagged1 in PEG-MAL hydrogels to repair bone; delivery of FTY720-loaded biomaterial scaffolds to repair oral cavity mucosa; delivery of commensal bacteria using hydrogels to enhance oral wound healing.
Our goal is to push the boundaries of what is currently known about facial bone and tissue repair, and ultimately use models to provide translational, clinical relevance, all while having fun!
Craniofacial Bone Regeneration
Craniofacial bone loss in children is a challenging clinical problem for which no regenerativestrategies are available. This type of bone loss is primarily treated with autologous bone grafting. Congenital absence of bone in the maxillary area is a defining facial characteristic of Alagille syndrome patients and may require bone grafting to restore maxillary alignment. Alagille syndrome is an autosomal dominantly inherited disorder that occurs primarily due to mutations in JAGGED1 and is associated with cardiac, biliary and bone phenotypes. Children with Alagille syndrome not only have maxillary bone hypoplasia, they also suffer from frequent bony fractures. Adults with Alagille syndrome have reduced bone mineral density and genome wide association studies revealed Single Nucleotide Polymorphisms in JAGGED1 were associated with reduced bone mineral density in otherwise unaffected adults. Together these data highlight the requirement of Jagged1 signaling during bone formation and that its absence causes multiple bony phenotypes, most noticeably maxillary hypoplasia. Jagged1 regulates multiple cell functions including cell survival, cell migration, and cell fate determination. Our initial work has established the requirement of Jagged1 during cranial neural crest (CNC) bone formation through the generation of a mouse model of Alagille syndrome with maxillary bone loss.
Publications:
Immunotherapy for Oral Wound Healing
Orofacial clefts are the most prevalent congenital defect and require palate surgery to allow proper feeding and maxillary growth. Due to adverse healing, 60% of these surgeries fail, leading to oronasal fistula (ONF). The ONF affects the child’s ability to eat, talk, and thus, the overall quality of life. Current clinical care to repair ONF uses human donor tissue but carries risk of infection and allograft rejection. As the oral microbiome is bacteria laden, proper wound healing is difficult without immunomodulatory intervention. Along with our collaborators, Drs. Nick Willett, Edward Botchwey, and Dennis Liotta we recently showed that locally delivering immunomodulatory drugs using scaffolds can promote a pro-regenerative oral environment and reduce off-target side effects. We hypothesize that delivering FTY720-loaded polymer scaffolds will enhance oral wound healing and reduce the occurrence of ONF. Integrating principles from both cellular and tissue engineering, we aim to characterize the mechanism by which localized delivery of FTY720 promotes regenerative environment through recruitment of pro-regenerative immune cells. These findings are of extreme importance as harnessing the effects of immunomodulation for oral wound healing provides greater implication for more personalized and efficacious treatment options for pediatric patients.
Publications:
Host-Microbiome Guided Oral Wound Healing
Wound healing has been studied extensively on the skin and particularly following intestinal injury. Intestinal wound healing efficiency is highly sensitive to environmental factors, especially the microbiome, where specific microbial community structures or supplementation with probiotic bacteria enhances the wound healing process. However, little is known about how the oral microbiome affects ONF wound healing. We directly address this gap in knowledge and show preliminary data that creating an ONF in a murine model results in marked changes in the microbiome composition with the complete disappearance of certain microbes and blooms of other bacterial taxa.Thus, our overall hypothesis is that the oral commensal microbiome exerts positive modulatory influences on oral wound healing and may limit ONF formation. Discovering specific bacterial taxa within the oral cavity or wound tissue that positively influence healing will be essential information for the characterization of an eubiotic oral microbiome for wound healing. Our experiments will also generate critical information for clinicians about the prudent use of antibiotics after cleft palate surgery and the effects of depleting the oral microbiome during healing. We will also substantiate the approach of the repletion of the oral commensal bacteria using hydrogel technology as the vehicle to enhance oral wound healing. Together, these studies will yield critical data to inform new therapeutic modalities to lower the prevalence of ONFs following cleft palate surgery.