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Dr. Michael Goggins MD, Professor
Departments of Pathology, Medicine and Oncology,
Johns Hopkins Medical Institutions
Title: Markers of pancreatic neoplasia and their clinical utility
Pancreatic ductal adenocarcinoma is the 4th leading cause of cancer death in the USA and one of the deadliest cancers. Our clinical trials demonstrate that screening individuals with an inherited predisposition to pancreatic cancer is effective at identifying pre-invasive neoplasms that can be cured by surgical resection. The goal of screening is to detect the earliest stage pancreatic cancers and lesions in the pancreas that have high-grade dysplasia. Although pancreatic imaging can identify most pancreatic cancers and IPMNs, it cannot identify microscopic high-grade pancreatic intraepithelial neoplasias (PanINs). Since resecting high-grade PanIN can be curative, accurate markers detectable in pancreatic fluids are needed to identify these lesions. Advances in our ability to detect low concentrations of mutant DNA are making this feasible. Pancreatic cysts are also a diagnostic challenge. Molecular evaluation of pancreatic cyst fluid using markers is likely to be an effective way to evaluate pancreatic cysts to determine which lesions require resection. A comprehensive understanding of the molecular abnormalities of pancreatic cancer precursor lesions (PanINs and IPMNs) is necessary to enable us to understand the timing of such abnormalities during neoplastic progression.
» CV (PDF/418KB)
Dr. Balveen Kaur
Associate Professor Department of Neurological surgery
Dardinger Laboratory of Neurosciences
The Ohio State University
Title: Impact of Tumor microenvironment on oncolysis.
The abstract is as below, I am attaching a photograph of myself.
Abstract: Oncolytic viral therapy has been explored widely as an option for cancer treatment. We have been investigating the role of tumor microenvironment in governing the efficacy of this therapy. We have identified induction of CCN1 an extracellular matrix (ECM) protein is induced upon infection with oncolytic HSV-1. We have subsequently identified that exogenous CCN1 in glioma ECM orchestrated a cellular antiviral response that reduced viral replication and limited cytolytic efficacy. Gene expression profiling and real time PCR analysis revealed a significant induction of type-I interferon responsive genes in response to CCN1 exposure. This induction is accompanied by activation of the cellular Jak/Stat signaling pathway. Both effects were mediated by the binding of CCN1 to the cell surface integrin α6β1, activating its signaling and leading to activation of interferon-α, which was essential for the innate antiviral effect. Together, our findings reveal how an integrin signaling pathway mediates activation of a type-I antiviral interferon response that can limit the efficacy of oncolytic viral therapy. Further, they suggest therapeutic interventions to inhibit CCN1-integrin α6 interactions to sensitize glioma to viral oncolysis.
» CV (PDF/251KB)
Dr. Aleksic Branko
G30 Associate Professor
Office of International Affairs, Department of Psychiatry
Title: Analysis of the VAV3 as new candidate gene for schizophrenia: evidences from voxel based morphometry and mutation analysis
OBJECTIVES: In recently completed Japanese GWAS of schizophrenia (JGWAS) one of the top association signals (within top 10 hits) was detected in the region of VAV3, a gene that maps to the chromosome 1p13.3. The associated SNP (rs1410403) was intronic common polymorphism located close to 3’ end of VAV3. SNP level association signal was followed-up in independent replication sample, and non-significant trend for association was detected. Direction of association was consistent, and meta-analysis for Japanese sample set provided statistical evidence for genetic association (P=0.0009, odds ratio=0.86). In order to complement JGWAS findings, we performed exon resequencing of VAV3 and we tested the association of rs1410403 with brain structure in healthy individuals and schizophrenic patients.
METHODS: We performed voxel based morphometry (VBM) and mutation screening of VAV3. Four independent samples were used in the present study: (1) for VBM analysis we used case control sample comprising 100 patients with schizophrenia and 264 healthy controls (2) 575 unrelated patients with schizophrenia and 564 subjects with no personal or family history of psychiatric disorders were selected for genome wide screening analysis, (3) for the replication analysis we used sample comprising 1511 cases and 1517 healthy controls and (4) mutation analysis was performed on a total of 321 patients suffering from schizophrenia.
RESULTS: The VBM analysis suggests that rs1410403 might affect the volume of the left superior and medial temporal gyri, which were reduced in patients with schizophrenia compared to healthy subjects. Moreover, four rare novel missense variants were detected in the present study. The mutations were followed-up in large independent case controls sample (>4000 subjects) and one of the novel variants was associated with schizophrenia.
CONCLUSIONS: We conclude that these results are suggestive of an association with schizophrenia at VAV3 locus, but that they could not be considered conclusive without further replications.
» CV (PDF/47KB)
» List of Papers (PDF/61KB)