top of page

Functional genomics

Genome sequencing technology continues to advance with ever increasing speed and efficiency and decreased cost. It is now possible to obtain genomic sequencing data in clinical time frame even during the prenatal period. However, the exponential and accelerated growth of genomic data has only exacerbated and underscores the difficulty in translating this data to clinically actionable information. For example, whether it is somatic sequencing data from tumors or germline sequencing data from congenital conditions, resolving the sequence information down to a causative gene has for the most part defied computational tools; often requiring experimental evidence to impute pathogenicity. Further, newer systems and tools need to be developed to handle the integration and analysis of genomic data.

Team science - our lab collaborates with human geneticists and data scientists to curate genes associated with congenital craniofacial conditions and interrogate these genes functionally in experimental models. We utilize human iPSC, mouse, and zebrafish models to elucidate the function of genes in craniofacial development.  For many genes required in craniofacial development, such as IRF6, ESRP1/2 and ALX1, we have developed zebrafish, mouse, and iPSC cell models and assays where we can also functionally test variants in these genes.



We consider multi-omics in a broad sense to mean integration of large datasets (genomic sequencing, RNA sequencing, proteomics, deep phenotyping, clinical outcomes) to reveal new insight or actionable information to drive scientific or clinical advances. For craniofacial conditions, we are interested in integrating morphometric data, clinical functional data, and molecular diagnosis, as intersection of data across independent approaches increases the significance and robustness of discovery.

Next Generation Treatments

Advances in gene editing and gene delivery are critical technology enablers of gene therapy applications now revolutionizing medicine and offering hope to patients afflicted with sickle cell disease, leukemia, diabetes and many others. We are developing gene therapy tools to improve treatment of craniofacial conditions.

As craniofacial surgeons, we are innovating biomaterials and devices for use in surgical procedures, to replace or enhance bone and soft tissue.


Clinical Outcomes

It is the patient and their problems that inspire our research.  The CHOP clinical craniofacial program is one of the most robust in the world, with regional, national, and international referral of high volume and high complexity craniofacial conditions. There is a long standing history of contribution from CHOP and Penn on treatment of craniosynostosis, cleft lip and palate, and other craniofacial conditions.

We are engaged in many clinical outcomes studies to refine surgical procedures, improve safety and patient experience, and initiate first-in-child clinical trials in order to advance craniofacial care for children and their families. Wherever possible, we reach out to patient groups to enhance patient advocacy and feedback. 

Formation of the vertebrate facial structures requires coordination of complex molecular and morphogenetic cues. The genes regulating facial development are well conserved across vertebrate species, where minor molecular variations contribute to dramatic alterations in form.

We take advantage of the versatility of forward and reverse genetics in zebrafish as a model to assay function of human cleft candidate genes and demonstrated that the zebrafish palate (ethmoid plate) is morphogenetically homologous to the mammalian primary palate (Dougherty, Development, 2013). We also showed that convergence and extension mechanisms operate in palate morphogenesis, and we are dissecting the Wnt pathway genetically (Rochard, Development, 2016; Kamel, Developmental Biology, 2013).

Advances in clinical treatment of congenital craniofacial malformations require improved understanding of the developmental genetic basis of facial morphogenesis. Our goal is to investigate fundamental genetic regulation of facial development, with focus on translating basic science discoveries to clinical treatments.

CLP Functional Genomics Pipeline


Vertebrate Craniofacial Morphogenesis


We are applying zebrafish to carry out high throughput functional genomics studies, to characterize human genes implicated in orofacial clefts (Mukherjee, Human Molecular Genetics, 2016; Gfrerer, Plastic and Reconstructive Surgery, 2014). We are also using zebrafish as the biological platform to identify chemicals that specifically regulate craniofacial morphogenesis, or even discover compounds that mitigate malformations (Kong, Chemistry & Biology, 2014).

With continued revolutionary advance in human gene sequencing approaches, there is pressing need to bridge the gap between whole genome analysis and clinical use of this data. Determination of pathogenicity of human gene variants is a major challenge in the field, limiting clinical usefulness of WGS information. We apply functional assays in iPSC and zebrafish models toward functional analysis of human gene variants associated with cleft and craniofacial anomalies (E BH Li, Plos Genetics, 2017).

bottom of page