Current Research and Scholarly Interests
My scholarly pursuits are primarily focused on the study of death and disease in the pediatric population. Most notably to characterize pediatric tumor pathology, evaluate abnormalities of the juvenile reproductive system, demonstrate the histologic and ultrastructural changes of metabolic disorders on specific organs, and elucidate new scientific techniques to aid in the study of childhood disease.
1. Ovarian Surface Epithelial Neoplasms:
Ovarian cancer is the fifth most common cause of malignancy in adult women; with those involving the surface epithelium of the ovary being the most common. In stark contrast, ovarian neoplasms account for approximately 1% of all childhood malignancies with those affecting the epithelium being extraordinarily rare. It is partially due to their low frequency that little is known about the overall incidence, histologic subtypes, optimal treatment strategies, and natural history of ovarian surface epithelial neoplasms in children.
2. Liver Pathology in Mitochondrial DNA Depletion Syndrome:
Mitochondrial disorders are rare causes of childhood disease and dysfunction. Syndromes caused by depletion of mitochondrial DNA (mtDNA) are exceptionally rare, but can often cause devastating outcomes. These depletion syndromes are caused by anomalous mtDNA or nuclear DNA encoding for mitochondrial proteins resulting in a quantitative reduction in mtDNA and abnormal oxidative phosphorylation. To date, three genes have been implicated in this process MPV17, polymerase gamma, and deoxyguanosine kinase. In neonates, these abnormalities most often manifest with hepatic and neurologic dysfunction; the hepatocerebral phenotype. Recognition of the clinical signs and symptoms of mitochondrial DNA depletion coupled with the histologic and ultrastructural features can result in early diagnosis and optimal treatment.
3. Liver Explant Pathology In Argininosuccinate Lyase Deficiency:
Argininosuccinate (ASA) lyase deficiency is the second most common urea cycle disorder in the pediatric population. It manifests in either a neonatal or late onset form with seizures, lethargy, and often hyperammonemia. Due to the risk of cognitive impairment, children are closely followed by monitoring serum ammonia levels and treated with arginine supplementation, dietary restriction, and recently liver transplantation. Characterization of the histologic features of livers in children with ASA lyase deficiency will aid pathologists in providing prompt diagnoses and allow clinicians to impart early therapy before the onset of life threatening complications and cognitive impairment.
4. Tissue Microarray Analysis of Small Volume Cellular Suspensions:
The use of small volume tissue samples in tissue microarray analysis has been plagued by inefficiency and poor reproducibility. Therefore, tissue samples such as cerebrospinal fluid, pleural fluid, bone marrow aspirates, and fine needle aspirates are often excluded from scientific research. A new technique developed by a team of researchers at Stanford University School of Medicine has made utilization of these low volume tissue samples possible. In fact, this technique can be used to establish diagnoses and confirm other ancillary testing results, such as gene expression arrays.
