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Utilizing a combination of tissue-based, cell-based, and molecular approaches, our research goals focus on abnormal telomere biology as it relates to cancer initiation and tumor progression, with a particular interest in the Alternative Lengthening of Telomeres (ALT) phenotype. In addition, our laboratories focus on cancer biomarker discovery and validation with the ultimate aim to utilize these novel tissue-based biomarkers to improve individualized prevention, detection, and treatment strategies.
Current projects include:
The evaluation of mechanisms of immune tolerance to cancer in mouse models of breast and pancreatic cancer. We have characterized the HER-2/neu transgenic mouse model of spontaneous mammary tumors.
This model demonstrates immune tolerance to the HER-2/neu gene product. This model is being used to better understand the mechanisms of tolerance to tumor. In addition, this model is being used to develop vaccine strategies that can overcome this tolerance and induce immunity potent enough to prevent and treat naturally developing tumors. More recently, we are using a genetic model of pancreatic cancer developed to understand the early inflammatory changes that promote cancer development.
The identification of human tumor antigens recognized by T cells. We are using a novel functional genetic approach developed in our laboratory. Human tumor specific T cells from vaccinated patients are used to identify immune relevant antigens that are chosen... based on an initial genomic screen of overexpressed gene products. Several candidate targets have been identified and the prevelence of vaccine induced immunity has been assessed .
This rapid screen to identify relevant antigenic targets will allow us to begin to dissect the mechanisms of tumor immunity induction and downregulation at the molecular level in cancer patients. More recently, we are using proteomics to identify proteins involved in pancreatic cancer development. We recently identified Annexin A2 as a molecule involved in metastases.
The analysis of antitumor immune responses in patients enrolled on vaccine studies. The focus is on breast and pancreatic cancers. We are atttempting to identify in vitro correlates of in vivo antitumor immunity induced by vaccine strategies developed in the laboratory and currently under study in the clinics. view less
Florin Selaru Lab
Research interests in the Florin Selaru Lab comprise the molecular changes associated with the transition from inflammatory states in the GI tract (colon, stomach, biliary tree) to frank cancers. In addition, our current research—funded by the AGA, FAMRI and the Broad Foundation—works to further the understanding of cancer development and progression in the gastrointestinal tract.
Research in the Ewald laboratory starts from a simple question: Which cells in a breast tumor are the most dangerous to the patient and most responsible for metastatic disease? To answer this question, we developed novel 3-D culture assays to allow real-time analysis of invasion. Our data reveal that K14+ cancer cells play a central role in metastatic disease and suggest that the development of clinical strategies targeting these cells will provide novel breast cancer treatments.
Francis Giardiello Lab
Research in the Francis Giardiello Lab focuses on the study of cancer and cancer chemoprevention in the gastrointestinal tract. This has included the investigation of the genetic basis of familial colorectal cancer and the use of genetic testing in the hereditary forms of colorectal cancer. We have a continuing interest in the study of the genotypic-phenotypic correlations in polyposis syndromes, which include familial adenomatous polyposis, juvenile polyposis and Peutz-Jeghers syndrome.
Franck Housseau Lab
The Franck Housseau Lab focuses on the role of the microbiome in colorectal tumorigenesis and on developing a better understanding of the tumor immune microenvironment. The lab is currently working to define the biomarkers of a pre-existing antitumor immune response in metastatic colorectal cancer to define a population of patients eligible for checkpoint blockade therapies.
The Gabelli lab research is focused on structural, mechanistic and functional aspects of enzyme activation that play a role in the biology of human diseases such as cancer, parasitic infection and cardiovascular disease. Their work seeks to:
1. Understand how molecular events at the recognition level coordinate and trigger events in the cells
2. Translate structural and mechanistic information on protein:protein interactions at the cytoplasmic level into preventive and therapeutic treatment for human disease.
To achieve a comprehensive understanding, they are studying cytoplasmic protein-protein interactions involved in regulation of pathways such as PI3K and Sodium Voltage gated channels. Their research integrates structural biology and chemical biology and it is focused on drug discovery for targeted therapies.
The GI Biomarkers Laboratory studies gastrointestinal cancer and pre-cancer biogenesis and biomarkers. The lab is led by Dr. Stephen Meltzer, who is known for his research in the molecular pathobiology of gastrointestinal malignancy and premalignancy. Research in the lab has led to several groundbreaking genomic, epigenomic and bioinformatic studies of esophageal and colonic neoplasms, shifting the gastrointestinal research paradaigm toward genome-wide approaches.
GI Early Detection Biomarkers Lab
Dr. Meltzer is an internationally renowned leader in the molecular pathobiology of gastrointestinal malignancy and premalignancy. He invented molecular methods to detect loss of heterozygosity in tiny biopsies, triggering an avalanche of research on precancerous lesions. He was the first to comprehensively study coding region microsatellite instability, leading to the identification of several important tumor suppressor genes. He performed several groundbreaking genomic, epigenomic and bioinformatic studies of esophageal and colonic neoplasms, shifting the GI research paradigm toward genome-wide approaches. He directed an ambitious nationwide validation study of DNA methylation-based biomarkers for the prediction of neoplastic progression in Barrett’s esophagus.
Dr. Meltzer founded and led the Aerodigestive Cancer and Biomarker Interdisciplinary Programs at the University of Maryland, also becoming associate director for core sciences at that school’s Cancer Center. He currently hol...ds an endowed professorship and is the director of GI biomarker research at Johns Hopkins.
The laboratory group focuses its efforts on the molecular genetics of gastrointestinal cancers and premalignant lesions, as well as on translational research to improve early detection, prognostic evaluation, and treatment of these conditions. Below, some examples of this work are described. view less