Sompop Bencharit, DDS, MS, PhD, FACP
Virginia Commonwealth University
Department of General Practice, School of Dentistry
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Department of Biomedical Engineering, College of Engineering
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Cerebral cavernous malformation (CCM) is a vascular anomaly in the brain that occurs naturally in 0.1 to 0.5% of the population. Genetic mutations at three loci are responsible for the inherited development of CCM. They encode three CCM proteins: Krit1 (Krev interaction trapped-1), OSM (Osmosensing scaffold for MEKK3 or malcalvernin), and PDCD10 (Programmed cell death 10).
In collaborations with Dr. Gary L. Johnson's laboratory at UNC, we have shown that all three CCM proteins interact with each other and form a signaling complex in the cell. PDCD10 stands out among these proteins because of its extremely conserved amino acid sequence from invertebrates to mammals. Mutations of PDCD10 represent about 10% of all CCM; however, the subsequent lesions are the most severe form. PDCD10 is also the only CCM protein that has no known domain or motif that would provide possible insight into function.
Our long term goals of this study are to understand how PDCD10 functions in physiologic vascular development and pathologic CCM development and to translate this basic knowledge from this CCM system to new preventive/therapeutic interventions for hemorrhagic stroke and other vascular malformations. We hypothesize that (1) PDCD10 regulates p38 activation through its interaction with OSM, and (2) PDCD10 participates in PDK1 signaling via its interactions with phospholipids, and PDK1. We further propose that these interactions are essential for endothelial migration and vessel formation. Understanding and manipulating complex protein-protein interactions required for physiological signaling during angiogenesis and vasculogenesis is an important step in developing prevention and treatment for hemorrhagic stroke.
Structural and functional analysis of cerebral cavernous malformation
Exploring salivary biomarkers for serum A1C
Over 20 million people live with diabetes, a quarter of whom have no knowledge of their diabetic condition. Therefore, there is a need to develop an effective screening tool for the disease, as well as a metric to monitor progression of diabetes. Monitoring blood sugar is commonly used to diagnose and monitor the progression of diabetic condition. Unfortunately, blood sugar level is not the most reliable tool and patient compliance can be an issue. Saliva is an attractive diagnostic fluid since it can be obtained non-invasively, with minimal training. Our research goal is to identify proteins in saliva that can be developed into a diagnostic tool for diabetes, as well as a tool to monitor blood sugar. An effective screening tool and a metric for monitoring disease progression can improve diabetic diagnosis and prevent morbidity. Measuring serum hemoglobin A1C, the most reliable tool in diagnosing and monitoring diabetes, requires laboratory support and professional interpretation. Certain salivary biomarkers are differentially expressed between type I or II diabetes and non-diabetic controls. However, there is limited numbers of study investigating the relationship between A1C and salivary biomarkers. The hypothesis is that the levels of expression of certain salivary biomarkers correlate with serum A1C levels. Novel salivary biomarkers will be explored and identified A1C-related salivary biomarkers will be monitored using mass-spectrometry. We enroll over 200 type I and type II diabetes.. Whole unstimulated saliva was collected at the same time of serum A1C measurement. Labeled-free mass spectrometry proteomics was used to monitor identified biomarkers in all samples.
Facial bone preservation and inflammatory responses of porous trabecular metal enhanced titanium implants immediately placed in extraction sockets
Surface-enhancement of titanium implants has been used successfully to maintain peri-implant tissue. However until recently this enhancement was merely a two-dimensional modification and only improved bone on-growth. A recent introduction of porous tantalum trabecular metal enhanced titanium implants (PTTM implants) promises a novel three-dimensional enhancement of implant surface modification allowing both bone in-growth and on-growth known also as osseoincorporation. While the technology is promising, it is not known if this new implant has any advantage in terms of improving bone remodeling around the dental implants, especially in an implant placed immediately after extraction in the esthetic zone. Preservation of facial bone, reduction of tissue inflammation, as well as providing patient’s comfort are among the most important factors in the success of immediate implant therapy. We hypothesize that the PTTM implants will 1) enhance facial bone preservation, 2) reduce inflammatory responses and 3) provide more comfort to the patient compared to conventional titanium implants. 30 patients with an unrestorable tooth in the anterior/premolar area will be recruited. Patients will be randomly assigned to have either conventional titanium or PTTM implants. The affected tooth will be extracted. An implant--either a conventional titanium or PTTM implant--will be immediately placed. A screw-retained provisional abutment will be placed. Patients will be seen at 1, 2, 4, and 8 weeks post-operatively to assess the level of pain/discomfort (using visual analog scale), measure soft tissue changes, and collect peri-implant fluids. At 8-12 weeks the implant will be restored with a definitive abutment/crown. Gingival crevicular fluid (GCF) and peri-implant fluid will be collected immediately before extraction and at 2, 4, and 8 weeks follow up visit. Conebeam CTscans and impressions will be performed preoperatively, and at 12 months after implant placement to assess the facial soft/hard tissue changes. Protein multiplex analysis will be used to determine the inflammatory mediators in the GCF and peri-implant fluid. The results will elucidate if the new PTTM implants provide better soft and hard tissue responses and comfort to the patient compared to conventional titanium implants. This may in the future give clinicians new guidelines for the use of this type of implant.