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  • Bert Vogelstein Laboratory

    The Bert Vogelstein Laboratory seeks to develop new approaches to the prevention or treatment of cancers through a better understanding of the genes and pathways underlying their pathogenesis.

    Our major focus is on cancers of the colon and rectum. We have shown that each colon neoplasm arises from a clonal expansion of one transformed cell. This expansion gives rise to a small benign colon tumor (called a polyp or adenoma). This clonal expansion and subsequent growth of the tumors appears to be caused by mutations in oncogenes and tumor suppressor genes, and the whole process is accelerated by defects in genes required for maintaining genetic instability. Mutations in four or five such genes are required for a malignant tumor to form, while fewer mutations suffice for benign tumorigenesis. As the mutations accumulate, the tumors become progressively more dangerous.

    Current studies are aimed at the further characterization of the mechanisms through which these genes act, the ident...ification of other genes that play a role in this tumor type, and the application of this knowledge to patient management. view more

    Research Areas: rectal cancer, colon cancer, genomics, pathogenesis

    Lab Website

    Principal Investigator

    Bert Vogelstein, M.D.

    Department

    Oncology

  • Brain Cancer Biology and Therapy Lab

    The goal of the Johns Hopkins Brain Cancer Biology and Therapy Laboratory is to locate the genetic and genomic changes that lead to brain cancer. These molecular changes are evaluated for their potential as therapeutic targets and are often mutated genes, or genes that are over-expressed during the development of a brain cancer. The brain cancers that the Riggins Laboratory studies are medulloblastomas and glioblastomas. Medulloblastomas are the most common malignant brain tumor for children and glioblastomas are the most common malignant brain tumor for adults. Both tumors are difficult to treat, and new therapies are urgently needed for these cancers. Our laboratory uses large-scale genomic approaches to locate and analyze the genes that are mutated during brain cancer development. The technologies we now employ are capable of searching nearly all of a cancer genome for molecular alterations that can lead to cancer. The new molecular targets for cancer therapy are first located by l...arge scale gene expression analysis, whole-genome scans for altered gene copy number and high throughput sequence analysis of cancer genomes. The alterations we find are then studied in-depth to determine how they contribute to the development of cancer, whether it is promoting tumor growth, enhancing the ability for the cancer to invade into normal tissue, or preventing the various fail-safe mechanisms programmed into our cells. view more

    Research Areas: brain cancer

    Lab Website

    Principal Investigator

    Gregory Riggins, M.D., Ph.D.

    Department

    Neurosurgery

  • Daria Gaykalova Lab

    The Daria Gakalova Lab defines the functional role of epigenetics in transcriptional regulation of head and neck squamous cell carcinoma (HNSCC) progression. To evaluate the whole-genome distribution of various histone marks, her team is using chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-Seq) for primary tissues, a method recently developed by her lab. The research group of Daria Gaykalova was the first to demonstrate the cancer-specific distribution of H3K4me3 and H3K27ac marks and their role in cancer-related gene expression in HNSCC. The research showed that an aberrant chromatin alteration is a central event in carcinogenesis and that the therapeutic control of chromatin structure can prevent the primary of secondary cancerization. Further preliminary data suggest that the differential enrichment of these disease-specific histone marks and DNA methylation correlate with alternative splicing events (ASE) formation. For this project, Dr. Gaykalova... and her team employed a novel bioinformatical tool for the detection of cancer-specific ASEs. Through thorough functional validation of the individual ASEs, the lab demonstrated that each of them has a unique mechanism of malignant transformation of the cells. Due to high disease specificity, ASEs represent the perfect biomarkers of the neoantigens and have direct application to clinical practice. view less

    Research Areas: Head and neck squamous cell carcinoma, Human papillomavirus, Alternative splicing, epigenetics, Chromatin structure, Cancer genomics, head and neck cancer

  • David Feller-Kopman Lab

    Research interests in the David Feller-Kopman Lab include improving the multidisciplinary treatment of patients with complex airway disease, investigating the physiology and pathophysiology of non-malignant central airway obstruction and pleural disease, and developing novel methods to teach procedural skills.

    Research Areas: medical education, non-malignant central airway obstruction, pathophysiology, physiology, COPD

    Principal Investigator

    David Feller-Kopman, M.D.

    Department

    Medicine

  • Head and Neck Cancer Clinical Trials and Tissue Bank

    The Johns Hopkins Head and Neck Cancer Tissue Bank enrolls patients and collects research specimens from Head and Neck Tumor patients, both cancerous and benign, with particular focus on Head and Neck Squamous Cell Cancer patients. It provides specimens to researchers both within the institution and outside.

    Research Areas: benign, malignant, cancer, tumor, head and neck tumors, Squamous cell carcinoma

  • Lonny Yarmus Lab

    Clinical trials conducted in the Lonny Yarmus Lab focus primarily on minimally-invasive diagnostic testing for patients with lung cancer and local therapy options for malignant airway obstructions. We investigate ways to improve the early diagnosis of lung cancer, as well as the treatment of later-stage cancer, using the least invasive methods possible. We are also part of the LIBERATE clinical study for patients who have difficulty breathing and suffer from severe emphysema.

    Research Areas: emphysema, interventional pulmonology, airway stenosis, minimally-invasive diagnostic testing, lung cancer, central airway obstructions, lung transplant

    Principal Investigator

    Lonny Yarmus, D.O.

    Department

    Medicine

  • Saowanee Ngamruengphong Lab

    Research in the Saowanee Ngamruengphong Lab focuses on methods for diagnosing and managing gastrointestinal conditions, including premalignant and malignant lesions of the gastrointestinal tract, esophageal cancer, colon polyps, and biliary and pancreatic disease. Our most recent work includes investigating a novel hybrid technique for closure of refractory gastrocutaneous fistula. We also conducted an international multicenter study that compared endoscopic ultrasound-guided pancreatic duct drainage with enteroscopy-assisted endoscopic retrograde pancreatography following Whipple surgery.

    Research Areas: colon polyps, cancer, endoscopy, pancreatic disease, gastric cancer, ultrasound, gastrointestinal

    Principal Investigator

    Saowanee Ngamruengphong, M.D.

    Department

    Medicine

  • The Burns Lab

    Our research laboratory studies the roles mobile DNAs play in human disease. Our group was one of the first to develop a targeted method for amplifying mobile DNA insertion sites in the human genome, and we showed that these are a significant source of structural variation (Huang et al., 2010). Since that time, our group has continued to develop high throughput tools to characterize these understudied sequences in genomes and to describe the expression and genetic stability of interspersed repeats in normal and malignant tissues. We have developed a monoclonal antibody to one of the proteins encoded for by Long INterspersed Element-1 (LINE-1) and showed its aberrant expression in a wide breadth of human cancers (Rodi? et al., 2014). We have demonstrated acquired LINE-1 insertion events during the evolution of metastatic pancreatic ductal adenocarcinoma and other gastrointestinal tract tumors (Rodi? et al., 2015). We have major projects focused on studying functional consequences of inh...erited sequence variants, and exciting evidence that these predispose to cancer risk and other disease phenotypes. Our laboratory is using a combination of genome wide association study (GWAS) analyses, custom RNA-seq analyses, semi-high throughput gene expression reporter assays, and murine models to pursue this hypothesis. view more

    Research Areas: cancer, DNA, malignant tumors

    Lab Website

    Principal Investigator

    Kathleen Burns, M.D., Ph.D.

    Department

    Pathology

  • Thomas Grader-Beck Lab

    Research in the Thomas Grader-Beck Lab aims to understand the pathogenesis of systemic autoimmune diseases—particularly systemic lupus erythematosus (SLE) and Sjögren’s syndrome—by taking a translational approach. Autoantibodies (antibodies that target self-molecules) are believed to contribute significantly to the disease process. We are studying mechanisms that may make self-structures immunogenic. We theorize that certain post-translational antigen modifications, which can occur in infections or malignant transformation, result in the expression of neoepitopes that spread autoimmunity in the proper setting. The team has combined studies that employ a number of mouse strains, certain gene-deficient mice and human biological specimens.

    Research Areas: Sjogren's syndrome, antibodies, autoimmune diseases, self-molecules, systemic lupus erythematosus

    Principal Investigator

    Thomas Grader-Beck, M.D., Ph.D.

    Department

    Medicine

  • William B. Isaacs Laboratory

    Prostate cancer is the most commonly diagnosed malignancy in men in the United States, although our understanding of the molecular basis for this disease remains incomplete. We are interested in characterizing consistent alterations in the structure and expression of the genome of human prostate cancer cells as a means of identifying genes critical in the pathways of prostatic carcinogenesis.

    We are focusing on somatic genomic alterations occurring in sporadic prostate cancers, as well as germline variations which confer increases in prostate cancer risk. Both genome wide and candidate gene approaches are being pursued, and cancer associated changes in gene expression analyses of normal and malignant prostate cells are being cataloged as a complementary approach in these efforts.

    It is anticipated that this work will assist in providing more effective methodologies to identify men at high risk for this disease, in general, and in particular, to identify new markers of prognostic... and therapeutic significance that could lead to more effective management of this common disease. view more

    Research Areas: cell biology, prostate cancer, molecular genetics

    Lab Website

    Principal Investigator

    William Isaacs, Ph.D.

    Department

    Urology

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