Our department has a robust and varied research enterprise. Learn more about the work being done in our labs via the descriptions below. Descriptions in include contact information and staff listings.
Investigating of the mechanistic connection between aging, cellular and/or mitochondrial metabolism and carcinogenesis with specific focus on the Sirtuin gene family.
Human sirtuins are the human homologs for the yeast and C. elegans longevity genes and breast cancers have one of the strongest correlations to age. Having this information, it is proposed that the primary sirtuin family knockout mice may present a novel group of models to establish, validate and investigate the well-established connection between aging, metabolism and cancer. To address this idea, over the past five years, we have constructed mice that have the three primary (Sirt1-3) sirtuins genetically deleted.
These each develop breast cancer, as well as other types of malignancies to varying degrees, and the levels of SIRT1-3 are also decreased in human cancer samples, as compared to normal tissues. In addition, the mechanism connecting the tumor permissive phenotype and the aberrant regulation of mitochondrial ROS, at least in part, in the Sirt3 knockout mouse has recently been published. Based on these results it seems clear that the primary sirtuin deacetylase proteins are tumor suppressor in several breast cancers as well as to a lesser extent in several other human malignancies.
Currently, our lab is utilizing the murine in vivo and in vitro models in several different projects examining the interactions of Sirt2 with proteins KRas, PKM2 and P53. We are also pursuing the efficacy of chemopreventive agents in luminal B breast malignancies. In addition we are studying the mechanistic link connecting Sirt2 and Sirt3 to cancers of the breast, pancreas, liver and lung. Finally, we have a group of neuroscientists examining the potential role of sirtuins in the development of neurodegenerative diseases that are associated with aging, particularly Parkinson’s.
For lab information and more, see David Gius', MD,PhD, faculty profile.
See Dr. Gius' publications in PubMed.
Contact Gius Lab
Contact the Gius Lab at 312-503-0332. You may also contact Dr. Gius directly at 312-503-2053 or via email.
The main focus of the Laboratory for Molecular Cancer Biology is to unravel the mechanistic link between aging and cancer with a focus on the regulatory role of post-translational modifications directed by sirtuins.
One of the fundamental observations in oncology is that increasing age is the strongest statistic variable that predicts for carcinogenesis. A fact that has emerged over the last several years is that aging is a complex process that appears to be regulated, at least in part, by several signaling protein families that have been identified in multiple species, including sirtuins, a relatively new gene family that was initially identified in S. cerevisiae and C. elegans. SIrtuins have been found to both increase life span and decrease spontaneous tumor development suggesting that they may regulate both processes. They appear to function as fidelity proteins and loss or decrease of function, which may occur during aging, creates a cell environment permissive for several age-related illnesses, including cancer. The significant role played by sirtuins can be explained by accumulating evidence establishing their pivotal role in regulating post-translational modifications (PTMs) in both histone and non-histone proteins involved in diverse cellular processes. Despite recent scientific interest in this field, there is still scarcity regarding the functional consequences of the role of these PTMs in cellular homeostasis. Our proposed studies take an integrative approach to current challenges in dissecting the functional role of sirtuin-directed PTMs in tumorigenesis which may bridge the gap between the observation that tumorigenesis increases with age and the limited information regarding the specific mechanisms underlying this phenomenon. By blending classic molecular/cellular biology, biochemistry and mouse genetics with large-scale proteomics, our ultimate research goal is to elucidate the function of sirtuins in maintaining cellular homeostasis which may provide novel mechanistic insights in different aspects of tumorigenesis.
See Dr. Vassilopoulos’ publications in Pubmed.
Contact Vassilopoulos Lab
You may contact the lab through the lab website: www.vassilopouloslab.com. Also, you may contact Dr. Athanassios Vassilopoulos directly at 312-503-0727 or via firstname.lastname@example.org.
Mohamed Ahmed, PhD
Yang Guo, MD, PhD
Mingming Zhang, PhD
Yijun Fan, BSc
Michael Bofu Li
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. Chipbased mRNA studies, gene promotoer analyses, immunohistochemistry and standard molecular approaches are being used.
Contact Woloschak Lab
Contact Dr. Woloschak at 312-503-4323 or via email.
Research Assistant Professor
David R Gius, MD/PhD
Professor in Radiation Oncology
Athanassios Vassilopoulos, PhD
Assistant Professor of Radiation Oncology
Gayle E Woloschak, PhD
Professor in Radiation Oncology and Radiology