Research

Genetic Alterations in Esophageal Adenocarcinoma: is a NCI-funded research project that has the goal of defining specific chromosomal regions that demonstrate gene amplification and then identifying the important cancer-related genes in these regions. This research utilizes technologies such as comparative genomic hybridization (CGH), Affymetrix oligonucleotide arrays, tumor tissue microarrays (TMA) and many others.
Lin Lin, M.D., Ph.D. and Zhuwen Wang, M.D., M.S. are key personnel involved in this project as well as collaborator Dr. Thomas Glover, Ph.D., Professor from the Department of Human Genetics.



Figure Below from Lin et al, Genes, Chromosomes and Cancer 45:319-331, 2006
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Identification of Genes and Proteins Associated with Therapeutic Response in Esophageal Adenocarcinoma: is a project that involved in identification of better predictors for the potential response of patients cancers to chemotherapeutic agents. Our research utilizes gene expression analyses with Affymetrix oligonucleotide arrays, two-dimensional liquid separation of proteins and tumor tissue microarrays and is directed by Andrew Chang, M.D., Assistant Professor of Surgery. Laura Maxon, M.S. is directly involved in this project and collaboration with David Lubman, Ph.D. Professor of Surgery and proteomics expert and Thomas Giordano, M.D., Ph.D. Department of Pathology



Figure from Zhao et al, Mol. Cell. Proteomics, Jul 8 [Epub ahead of print], 2006.


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Fig. 6 Representative samples from TMA for Rho-GDP dissociation inhibitor, beta (ARHGDIB) (a-d). Lamin A/C (e-h) and α -enolase (i-j) in Barrett’s metaplasia and esophageal adenocarcinoma.



Molecular Characterization of Lung Cancer: involves research that examines the gene expression profiling of adenocarcinoma and squamous cell carcinomas of the lung to identify genes and gene profiles predictive of patient prognosis and to identify patients with early stage cancers who might benefit from adjuvant therapy. Dr. Beer is currently leading a multi-institution collaboration that is funded by NCI and has profiled over 500 lung adenocarcinomas.



Figure from: Beer et al, Nature Medicine 8:816-824, 2002.
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Fig. 4 a Gene expression patterns determined using agglomerative hierarchical clustering of the 86 lung adenocarcinoma against the 100 survival-related genes (Table 1) identified by the training- testing, cross validation analysis. Substantially elevated (red) or decreased (green) expression of the genes are observed in individual tumors. Some tumors (black arrow and expanded area) show extremely elevated expression of specific genes.



Identification of Autoantibodies in Esophageal and Lung Cancer: is a NCI-funded project that is part of the Early Detection Research Network (EDRN) and in collaboration with Arul Chinnaiyan, M.D., Ph.D. Associate Professor in the Department of Pathology. The goal of these studies is to identify autoantibodies that are present in the serum of cancer patients and directed against specific proteins in these cancers. By detecting these autoantibodies the early detection of cancer is potentially achieved. Dr. Guoan Chen, M.D., Ph.D. provides a major effort on this project.


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Figure 1 Schematic representation of the phage-epitope microarray approach to characterize the humoral immune response to lung cancer. A cDNA library was constructed from a pool of total mRNA isolated from 7 lung cancer tissues (Step 1-3). After digestion, the cDNA library was inserted into the T7 bacteriophage vector (Step 4). The T7 fusion vectors were then packaged into T7 phages to generate a lung cancer cDNA phage display library (Step 5). Four rounds of affinity selection (biopanning) were performed (Step 6). Subsequently, enriched lung cancer/control specific epitope clones were cultured on LB agar plates. Single colonies were randomly selected into 96-well plates (Step 7). Phage clone lysates were then printed onto nitrocellulose coated slides using a robotic arrayer to create a 2300 element phage-epitope microarrays (Step 8). Cy5-labeled (red fluorescent dye) anti-human IgG antibody was used to detect human serum IgGs reactive to epitope clones, while a Cy3-labeled (green fluorescent dye) antibody was used to detect the phage capsid 10B protein in order to control for spotting (Step 9). Thus, if a phage clone carries an epitope which is reactive to human IgG, after scanning, this spot will be represented as yellow or red in color, otherwise, the spot will remain green, representing non-reactive clones (Step 10). The immunomic profiles are then analyzed using several statistical approaches.