Institute of Molecular Cancer Research
Director: Josef Jiricny
(Molecular and Cell Biology) Transition through the cell cycle is regulated by the timely assembly of cyclins and cyclin-dependent kinases (Cyc-CDKs). This, in turn, is under the control of signals coming from the environment and from within the cell. Failure of a single wheel at any point in this mechanism either impairs or accelerates growth. Focus of our studies is the network of signals triggered by DNA damage and controlling the onset of mitosis.
(Molecular and Cell Biology, Quantitative Biology and Systemsbiology) DNA of all living organisms is subject to extensive modification by a plethora of endogenous and exogenous agents. Efficient maintenance of DNA by a large repertoire of repair pathways ensures that the genomes of these organisms can fulfill their roles as sources of genetic information for future generations, as well as templates for the synthesis of RNA. Failure to keep DNA free of damage leads to senescence and cancer. We focus primarily on the study of DNA repair mechanisms in human cells, the malfunction of which is linked to disease.
(Molecular and Cell Biology) Our research takes advantage of molecular biology, cell biology and structural approaches to study DNA replication stress and its contribution to genome instability. We aim to understand the mechanistic basis of genome rearrangements arising during perturbed DNA replication, leading to cancer and other human syndromes. We also plan to structurally investigate the mechanism of action of common cancer chemotherapeutic drugs, known to exert their cytotoxicity via DNA replication interference.
(Molecular and Cell Biology, Quantitative Biology and Systemsbiology) My laboratory studies the bacterial pathogen Helicobacter pylori. Helicobacter infects the human stomach and causes gastritis, ulcers and cancer. Using animal and cell culture models of this host-pathogen interaction, we attempt to understand how the infection and the resulting inflammation cause cellular transformation and which genetic factors, of both the host and the pathogen, determine disease outcome.
(Molecular and Cell Biology, Human Biology) How do cells respond to DNA damage? Our lab is trying to discover novel mechanisms of the regulation of DNA repair proteins which are playing important roles in cancer biology. We are investigating the molecular and genetic basis of the DNA damage response mainly in human cancer cell lines, often in combination with biochemical approaches.
(Molecular and Cell Biology, Human Biology) Homologous recombination (HR) provides a mechanism for accurate repair of DNA double-strand breaks and single-strand gaps. However, if executed improperly, HR can result in chromosomal rearrangements, a hallmark of tumorigenesis and tumor progression. We study the mechanisms that cells use to suppress aberrant recombination events.
(Molecular and Cell Biology, Human Biology) Neoplasms of the large intestine, like tumors of other tissues, are the endpoint of a series of genetic and epigenetic alterations of chromatin. We are attempting to identify molecular markers of colorectal tumor formation and progression, with particular emphasis on those specific to tumors with defects in the DNA mismatch repair and propensity for silencing gene expression through epigenetic modifications of DNA and histones. To this aim, several techniques of molecular biology, biochemistry and cell biology are used, along with high-throughput screening procedures such as microarray analysis of the transcriptome of tumor cells. This research is linked to the clinics.
(Molecular and Cell Biology) We are studying the role of the tumor microenvironment on tumor growth and metastatic dissemination. In particular, we examine the role of tumor associated macrophages (TAMs) in animal and cell culture models. TAMs promote tumor growth in many human and murine tumors. To assess the role of TAMs we use a depletion method which kills the macrophages. The method is based on the phagozytosis of small liposomes which contain bisphosphonates that are toxic to the TAMs. TAM depletion is a tool to study the tumor microenvironment and to use it as adjuvant tumor therapy approach.