Viral and Environmental Causes of Cancer
Research on the viral and environmental origin of specific cancers.
Labs in This Area
Biomarker discovery and biomarker applications to epidemiological research
Recent findings suggest that more than 70% of the risk for developing chronic diseases and cancers are due to environmental factors, which include interactions between our environment and our genes. However, the role of the environment in disease etiology remains largely unknown. To address this need, research in my laboratory is focused on biomarker discovery and targeted methods that utilize simple and non-invasive blood collection strategies to extend biomarker applications to epidemiological research.
A major focus of my research is on an important class of chemical toxicants, reactive electrophiles. Because electrophiles are reactive, adducts of abundant blood proteins are used as biomarkers of exposure. Since stable adducts persist in the blood for the life span of the protein, adducts reflect an integration of exposure over weeks to months. We are applying an “adductomics” approach to a single nucleophilic ‘hot spot” on human serum albumin (HSA), HSA-Cys34, to generate adduct maps as molecular fingerprints of exposure. These adduct maps can be compared across groups to pinpoint candidate biomarkers. We are currently applying this strategy to investigate unknown risk factors associated with several cancers, congenital disorders and chronic diseases, including ovarian cancer, multiple myeloma, cleft lip and cleft palate, spina bifida and cardiovascular disease.
A second line of research in my laboratory focuses on the logistics of measuring biomarkers to assess environmental exposures in population-based research. An obstacle to the measurement of biomarkers is the requirement for venipuncture to obtain samples, which is expensive, invasive and needs to be performed by a trained phlebotomist near a laboratory where the blood can be immediately processed. In contrast, dried blood spots (DBS)—drops of whole blood collected on filter paper—are a simple and non-invasive alternative that can be collected in non-clinical settings. Current DBS projects in our laboratory are focused on prenatal, early childhood and adult exposures to toxic metals, including lead, arsenic, mercury and cadmium. We have several ongoing collaborative projects applying DBS to assess heavy metal exposures in newborns using state-archived DBS (retrospective studies) and in pediatric populations and young children (prospective studies) using a newly developed blood collection device (Funk & McDade, Patent Pending).
Future studies are planned to combine both lines of my research and apply adductomics to DBS samples. In collaboration with the CDC’s Centers for Birth Defects Research and Prevention, we will be obtaining newborn DBS from State Public Health Laboratories to explore unknown prenatal risk factors for a variety of birth defects.
For more information visit the faculty profile of William Funk, PhD.
See Dr. Funk's publications in PubMed.
Targets and functions of miRNAs encoded by the human herpesvirus Kaposi’s sarcoma-associated herpesvirus (KSHV)
Viruses commonly modify their cellular environment to optimize viral replication and persistence. Much has been learned about the intervention of viral proteins with cellular pathways. More recently, it has become clear that herpesviruses also encode large numbers of microRNAs (miRNAs). The modest amount of space miRNA precursors occupy in the viral genome, their lack of immunogenicity and their potential as regulators of gene expression make miRNAs ideal candidates for viral effectors.
The lab’s research focuses on identifying targets and functions of miRNAs encoded by the human herpesvirus Kaposi’s sarcoma-associated herpesvirus (KSHV). KSHV causes cancer in immuno-compromised individuals. The clinically most relevant KSHV-induced disease is Kaposi’s sarcoma (KS), a complex tumor driven by KSHV-infected endothelial cells. Due to the AIDS epidemic, KS has become the most common cancer in parts of Africa. KSHV also infects B lymphocytes and can consequently cause B cell lymphomas, including primary effusion lymphoma (PEL). KSHV constitutively expresses viral miRNAs from 12 precursors, suggesting a role of these miRNAs in viral replication and pathogenesis.
My lab is currently pursuing the comprehensive identification of mRNA targets of these miRNAs in primary effusion lymphoma cell lines and KSHV-infected endothelial cells. Our data suggest that, together, the KSHV miRNAs directly target hundreds of cellular mRNAs encoding proteins with roles in several different biological pathways. Our goal is to use this knowledge to characterize the most important functions of the KSHV miRNAs.
See Dr. Gottwein's publications on PubMed.
Contact Dr. Gottwein at 312-503-3075 or the lab at 312-503-3076.
Environmental, genetic and epigenetic risk factors for disease
Dr. Hou’s research interest lies in integrating traditional epidemiologic methods with the ever-advancing molecular techniques in multi-disciplinary research focusing on identifying key molecular markers and understanding their potential impact on disease etiology, detection and prevention.
Dr. Hou’s major research efforts to date have focused on two areas: 1) identification of risk factors that may cause chronic diseases; and 2) identification of biomarkers that serve as indicators of an individual’s past exposure to disease risk factors and/or predict future disease risks and/or prognosis. The environmental/lifestyle risk factors that Dr. Hou has studied include air pollution, pesticides, overweight, physical inactivity and reproductive factors in relation to chronic diseases. The biomarkers that Dr. Hou has investigated include genetic factors (i.e., polymorphisms, telomere length shortening, mitochondria DNA copy number variations) and epigenetic factors (i.e., DNA methylation, histone modifications and microRNA profiling). Her over-arching research goal is to understand the biological mechanisms linking environmental risk factors with subclinical or clinical disease development to ultimately lead to development of effective strategies for prevention of chronic diseases.
In addition to being a PI of several NIH funded grants, Dr. Hou is the co-director and Co-PI of the Northwestern Consortium for Early Phase Cancer Prevention Trials of the Division of Cancer Prevention (DCP) Consortia, National Cancer Institute.
For more information visit the faculty profile of Lifang Hou, MD, PhD.
See Dr. Hou's publications in PubMed.
Molecular biology of human papillomaviruses (HPV) and their association with cervical cancer
Our efforts are divided into two main categories:
- An examination of how the viral oncoproteins E6 and E7 contribute to the development of malignancy
- Studies on the mechanisms controlling the viral life cycle in differentiating epithelia
More than 100 distinct types of human papillomavirus have been identified and approximately one-third specifically target squamous epithelial cells in the genital tract. Of these genital papillomaviruses, a subset including types 16,18 and 31 have been shown to be the etiological agents of most cervical cancers.
One of our goals is to understand why infection by specific HPV types contributes to the development of malignancy. For these studies we have examined the interaction of the oncoproteins E6 and E7 with cellular proteins. In particular, E6 binds the p53 protein and facilitates its degradation by a ubiquitin-mediated pathway. It also activates telomerase as well as associates with PDZ-domain containing proteins. The interactions of the E6 and E7 proteins with these cellular proteins are being examined at both the biochemical and genetic level.
In examining the papillomavirus life cycle, we have used organotypic tissue culture systems to faithfully reproduce the differentiation program of epithelial cells in the laboratory. Using this system, the viral life cycle has been duplicated. We are studying the mechanisms that regulate viral DNA replication, cell entry, immune evasion and gene expression. These studies should provide insight into viral pathogenesis as well as the mechanisms regulating epithelial differentiation.
See Dr. Laimins' publications on PubMed.
Contact Dr. Laimins at 312-503-0648 or the lab at 312-503-0650.
Epstein-Barr virus (EBV) and herpes simplex virus (HSV) entry, replication and pathogenesis.
Research in the Longnecker laboratory focuses on herpes simplex virus (HSV) and Epstein-Barr virus (EBV). These viruses typically cause self-limiting disease within the human population but both can be associated with serious complications. EBV is associated with variety of hematopoietic cancers such as African Burkitt lymphoma, Hodgkin Lymphoma and adult T-cell leukemia. EBV-associated lymphoproliferative disease occurs in individuals with congenital or acquired cellular immune deficiencies. The two notable epithelial diseases associated with EBV infection are nasopharyngeal cancer and oral hairy leukoplakia. Similar to EBV, HSV latent infections are very common in humans. HSV typically does not cause severe disease but is associated with localized mucocutaneous lesions, but in some cases can cause meningitis and encephalitis. The Longnecker laboratory focuses on several aspects of EBV and HSV replication and pathogenesis. First, the molecular basis EBV transformation and how it relates to cancer is being investigated. The laboratory is currently screening selective inhibitors that may be beneficial in EBV-associated cancers such as Hodgkin lymphoma, Burkitt lymphoma and proliferative disorders that occur in HIV/AIDS and transplant patients. Second, the laboratory is investigating herpesvirus latency in the human host and pathogenesis associated with infections in humans. In this regard, the laboratory is developing animal models for EBV and HSV infections. Finally, the laboratory is investigating the function of herpesvirus encoded proteins and the cellular receptors that are important for infection both using in vivo culture models as well as animal models. Ultimately, studies by the Longnecker laboratory may provide insight for the development of novel therapeutics for the treatment of herpesvirus infections in humans and better understanding of the herpesvirus life cycle in the human host
For lab information and more, see Dr. Longnecker's faculty profile
See Dr. Longnecker's publications on PubMed.
Contact Dr. Longnecker at 312-503-0467 or the lab at 312-503-0468 or 312-503-9783.
Studying radiation-induced mutations in radiation-induced cancers; DNA-TiO2 nanoparticles; Radiosensitivity/motor neuron disease.
The Woloschak Lab members focus their research on three main areas.
The Janus Project: Studying radiation-induced mutations in radiation-induced cancers
This 30 year, $200 million set of experiments were performed at 150 laboratories and then terminated before the data were completely analyzed. Funded by the Department of Energy and National Aeronautic and Space Administration, department radiobiologists will continue the data analyses.
Members of the Woloschak laboratory have assumed responsibility from Argonne National Laboratory for archiving tissue associated with 30,000 mice and 4,000 dogs that received various doses and dose-rates of radiation.
These studies examined the effects of dose-rate on radiation-induced toxicities and radiation-induced cancer. They are analyzing cancer cells from these tissues to find differences in mutational spectra that occur in tumors induced in radiation-exposed animals compared to those that occur in spontaneous tumors. Recent scientific concerns about very low dose exposures makes this effort particularly important.
- University of Chicago
- Bundewehr Radiobiology Institute in Munich
- Argonne National Lab
The researchers have combined the functional properties of the biomolecule DNA and the inorganic compound TiO2. The project is oriented to investigating the functional use of these nanocomposites for intracellular manipulation, imaging and gene silencing.
Radiosensitivity/motor neuron disease
The project's purpose is to better understand the molecular basis for the combined abnormalities from a molecular-cellular perspective. Chip-based mRNA studies, gene promoter analyses, immunohistochemistry and standard molecular approaches are being used.
Contact Woloschak Lab
Contact Dr. Woloschak at 312-503-4323 or via email.