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.

The Zhu lab is focused on characterizing the activities of large collection of proteins, building signaling networks for better understanding the mechanisms of biological processes, and identifying biomarkers in human diseases and cancers. More specifically, our group is interested in analyzing protein posttranslational modifications, and identifying important components involved in transcription networks and host-pathogen interactions on the proteomics level, and biomarkers in human IBD diseases.

The Devreotes Laboratory is engaged in genetic analysis of chemotaxis in eukaryotic cells. Our long-term goal is a complete description of the network controlling chemotactic behavior. We are analyzing combinations of deficiencies to understand interactions among network components and carrying out additional genetic screens to identify new pathways involved in chemotaxis. A comprehensive understanding of this fascinating process should lead to control of pathological conditions such as inflammation and cancer metastasis.

The Shenderov Lab focuses on the elucidation of the mechanisms of immune response and resistance to immunotherapy in Prostate Cancer. This has led to clinical and basic research investigating the presumptive checkpoint inhibitor B7-H3. In pursuit of understanding biomarkers or resistance and response, and regulatory molecules of immune response, we utilize artificial intelligence, immunogenomics, and spatial proteomics and transcriptomics in the laboratory and at the bedside using clinical trial correlative samples.

The lab currently focuses on identifying genetic alterations in cancer affecting sensitivity and resistance to targeted therapies, and connecting such changes to key clinical characteristics and novel therapeutic approaches. We have recently developed methods that allow noninvasive characterization of cancer, including the PARE method that provided the first whole genome analysis of tumor DNA in the circulation of cancer patients. These analyses provide a window into real-time genomic analyses of cancer patients and provide new avenues for personalized diagnostic and therapeutic intervention.

Research in the Liliana Florea Lab applies computational techniques toward modeling and problem solving in biology and genetic medicine. We work to develop computational methods for analyzing large-scale sequencing data to help characterize molecular mechanisms of diseases. The specific application areas of our research include genome analysis and comparison, cDNA-to-genome alignment, gene and alternative splicing annotation, RNA editing, microbial comparative genomics, miRNA genomics and computational vaccine design. Our most recent studies seek to achieve accurate and efficient RNA-seq correction and explore the role of HCV viral miRNA in hepatocellular carcinoma.

Our Molecular Oncology lab seeks to understand the genomic wiring of response and resistance to immunotherapy through integrative genomic, transcriptomic, single-cell and liquid biopsy analyses of tumor and immune evolution. Through comprehensive exome-wide sequence and genome-wide structural genomic analyses we have discovered that tumor cells evade immune surveillance by elimination of immunogenic mutations and associated neoantigens through chromosomal deletions. Additionally, we have developed non-invasive molecular platforms that incorporate ultra-sensitive measurements of circulating cell-free tumor DNA (ctDNA) to assess clonal dynamics during immunotherapy. These approaches have revealed distinct dynamic ctDNA and T cell repertoire patterns of clinical response and resistance that are superior to radiographic response assessments. Our work has provided the foundation for a molecular response-adaptive clinical trial, where therapeutic decisions are made not based on imaging but based on molecular responses derived from liquid biopsies. Overall, our group focuses on studying the temporal and spatial order of the metastatic and immune cascade under the selective pressure of immune checkpoint blockade with the ultimate goal to translate this knowledge into “next-generation” clinical trials and change the way oncologists select patients for immunotherapy.

The Gregg Semenza Lab studies the molecular mechanisms of oxygen homeostasis. We have cloned and characterized hypoxia-inducible factor 1 (HIF-1), a basic helix-loop-helix transcription factor. Current research investigates the role of HIF-1 in the pathophysiology of cancer, cerebral and myocardial ischemia, and chronic lung disease, which are the most common causes of mortality in the U.S.

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.

The main research interests of the James Hamilton Lab are the molecular pathogenesis of hepatocellular carcinoma and the development of molecular markers to help diagnose and manage cancer of the liver. In addition, we are investigating biomarkers for early diagnosis, prognosis and response to various treatment modalities. Results of this study will provide a molecular classification of HCC and allow us to identify targets for chemoprevention and treatment. Specifically, we extract genomic DNA and total RNA from liver tissues and use this genetic material for methylation-specific PCR (MSP), cDNA microarray, microRNA microarray and genomic DNA methylation array experiments.