Cancer Biology Research Overview - Molecular Pathology

Research Overview - Cancer Biology

Cancer is now a leading cause of death-but it was not always that way! In the United States in 1900, the average life-span was 48 years old and 3.7% of the population died of cancer. By 1997, the average life-span increased to over 76 years, and 23.3% of individuals die of cancer. More people die of cancer because cancer is a principally a disease of aging caused by the accumulation of mutations that ultimately produce a cell capable of uncontrolled and infinite proliferation. These mutations activate signal transduction and cell division pathways, inhibit programmed cell death, alter cellular differentiation, promote metastasis, and prevent DNA repair.

SIGNAL TRANSDUCATION AND CELL DIVISION: Dr. Karin is a leader in the field of signal transduction and gene regulation by transcription factors that have the potential of becoming oncogenic by mutation. Signal transduction cascades in normal and tumor cells are generally controlled by protein kinases and phosphatases. Dr. Karin's lab has characterized some of the key oncogenic protein kinases such as Jun, Fos, and NFkB. Dr. Pasquale, whose work spans both neurosciences and cancer, studies how the Eph receptor stimulates tumor growth and angiogenesis. Dr. Walter focuses on protein phosphatase 2A, one of the most predominant serine/threonine-specific phosphatases involved in cell cycle regulation and signal transduction. Of special interest is the question how this phosphatase may act as a tumor suppressor. Dr. Feng focuses on the role of the Shp-2 tyrosine phosphatase and of a variety of adaptor proteins in transducing cell division signals from activated cytokine receptors to the nucleus.

INHIBITION OF CELL DEATH (APOPTOSIS): Programmed cell death has become a major focus in cancer research because many cancers have lost the ability to undergo apoptosis when treated with therapeutic drugs. Dr. Reed has made major contributions to our understanding of the diverse mechanisms that control apoptosis. He also attempts to develop anti-cancer drugs that enhance apoptosis. Dr. Salvesen is an expert in caspases, which are the key regulators in the pathways leading to apoptosis. Dr. Gottlieb focuses on mechanisms of apoptosis arising from ischemia or from activation of the Fas pathway. Dr. Frisch has discovered a special form of apoptosis called anoikis that plays a role in tumor metastasis. He also investigates the adenovirus E1a protein, which can function as a tumor suppressor and might be used against human cancers.

ALTERED CELL DIFFERENTIATION: Dr. Kamps discovered the first chimeric transcription factor in human cancer (E2a-Pbx1; found in human pre-B cell leukemia), and demonstrated that it blocks differentiation of blood cell progenitors in the bone marrow. He currently studies how the Hox, Meis, and Pbx family of homeodomain transcription factors control normal blood cell differentiation and how either their enforced expression or mutation produces leukemia in humans. Dr. Oshima investigates the role of the Ets2 transcription factor in mammary gland tumor development. In particular, he is interested in how Ets2 modulates interaction of breast cancer with stromal cells. Dr. Glass focuses on the mechanisms by which coactivators and corepressors function biochemically to regulate development. Such interactions are altered in leukemia oncoproteins, such as PML-RAR and PLZF-RAR, which disrupt normal myeloid differentiation, which results in the production of macrophages and neutrophils.

CANCER METASTASIS: Metastasis is a complex process that involves changes at the cancer cell surface. Dr. Quigley's laboratory studies the role of extracellular proteases in tumor metastasis and tumor angiogenesis. Dr. Fukuda studies the roles of cell surface oligosccharides in cell-cell interaction.

DNA REPAIR: Mutations in enzymes involved in DNA-repair is a major factor in tumor development. Dr. Perucho studies mechanisms that produce such genetic instability in cancer cells, and which generate mutations that target other oncogenes and tumor suppressor genes.

ANTI-CANCER DRUGS: The goal of cancer research today is to understand the biochemical functions of mutant cancer genes so that highly selective drugs having low overall toxicity can be used to eliminate specific cancers. Dr. Ely uses x-ray cristallography, NMR, circular dichroism, and molecular modeling to look at protein-protein interaction. Her aim is to define interaction surfaces and use them as targets for therapeutic intervention.

Training for Careers in Biomedical Research

Training for Careers in
Biomedical Research