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.

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 holds 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.

At the brain tumor laboratory, Henry Brem, M.D. and Betty Tyler, along with more than 350 trainees, have conducted scientific research, contributed to scientific literature, amended clinical practice, and illuminated new pathways for improving clinical outcomes.

The laboratory has advanced the understanding of gene therapy, angiogenesis, intracranial implantation of biodegradable polymers to treat malignant glioma, tumor genetics and proteomics, microchip drug delivery and drug resistance studies. Dr. Brem and his colleagues have designed and led many multi-institutional clinical trials to improve and expand the range of therapeutic options for patients with brain tumors.

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 large 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.

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 identification of other genes that play a role in this tumor type, and the application of this knowledge to patient management.

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.

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 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 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.