Members

nyt-headshot.jpgNatalia Tretyakova, Professor
Department of Medicinal Chemistry
College of Pharmacy

The focus of our research is to investigate the structural basis for carcinogenic and anticancer activity of DNA- and protein-modifying agents. Synthetic methodologies are developed to prepare structurally modified nucleosides and amino acids representing carcinogen- and drug-induced DNA and protein adducts. The effects of nucleobase modifications on DNA structure and stability are determined by NMR spectroscopy, mass spectrometry, CD spectroscopy, and computer modeling of chemically altered DNA. Biological mass spectrometry techniques are employed to quantify the formation of DNA and protein adducts in vivo. These studies identify the molecular targets of exogenous and endogenous electrophiles and provide an insight into the origins of their biological activity.
 

demerathEllen Demerath, Associate Professor
Division of Epidemiology & Community Health
School of Public Health

My research looks at the role that genes play in the developmental origins of chronic disease. Specifically I research obesity, body composition, genetic epidemiology, and cardiovascular disease risk factors in infancy and childhood with the goal to help prevent chronic disease.
 

wguanWeihua Guan, Assistant Professor
Division of Biostatistics
School of Public Health

My research focuses on statistical analysis and methodology development related to epigenome-wide association studies.  We aim to identify novel epigenetic markers and mechanism underlying complex diseases and risk factors.

 

timothy-hallstromTimothy Hallstrom, Assistant Professor

Department of Pediatrics, Pediatric Blood and Marrow Transplant (BMT) Center Microbiology, Immunology and Cancer Biology (MICaB) Ph.D. Graduate Program

The Hallstrom laboratory is studying the cellular mechanisms controlling Rb/E2F induced apoptosis during normal proliferation and in cancer development. Normal cellular proliferation is tightly regulated by cell size, mitogenic stimulation and absence of signals that block proliferation. The retinoblastoma (Rb) protein is a pivotal regulator of entry into the cell cycle and, importantly, disruption of various components of this control pathway leads to deregulated proliferation that underlies the development of many forms of cancer. Rb regulation of cell cycle progression and tumorigenesis is dependent on its control of E2F transcription factor function, a family of proteins that control expression of genes required for proliferation. Further work has highlighted the role of E2F proteins, particularly E2F1, in forming the link between the deregulation of Rb pathway activity and induction of p53-dependent apoptosis. E2F1 apoptosis induction is believed to serve a tumor-suppressive mechanism by eliminating cells that have sustained an oncogenic mutation which activates the Rb pathway.
 

kassieFekadu Kassie, Assistant Professor
Veterinary Clinical Sciences,
College of Veterinary Medicine

Research in the Kassie laboratory focuses on preclinical development of chemopreventive agents against lung cancer. Chemoprevention is a relatively new field of cancer research and seeks to reverse, suppress, prevent or delay the carcinogenic process either by blocking the development of early lesions or by inhibiting the progression to invasive cancer. Despite improvements in early detection, diagnosis and treatment of lung cancer, this disease is still the leading cause of cancer related mortality in the U.S. and worldwide. One potential approach to reduce lung cancer mortality is chemoprevention. Our laboratory follows a unique strategy to identify lung cancer chemopreventive agents having acceptable safety and efficacy profiles to warrant human clinical trials. Agents identified, based on published epidemiological or in vitro studies, as promising chemopreventive agents will be administered orally to mice, and efficacy confirmed and target organ concentrations at efficacious dose determined. Subsequently, in vitro studies will be performed, using concentrations achieved at target organ, to determine the potential mechanisms of the chemopreventive agent and identify biomarker of efficacy. This will be followed by further studies in animal models to corroborate the in vitro biomarker findings and assess the correlation between efficacy and change in biomarker level.
 

jpankowJim Pankow, Professor
Division of Epidemiology & Community Health
School of Public Health

I am an epidemiologist whose long-term research goal is to identify and characterize risk factors for cardiovascular disease, type 2 diabetes, and other chronic conditions of aging. During my career I have helped assemble large genetic epidemiologic cohorts of cardiovascular disease, investigated genetic determinants of proteins involved in inflammation, hemostasis, and cellular adhesion, researched novel risk factors for type 2 diabetes, including genetic and epigenetic determinants, and evaluated new methods and approaches in statistical genetics in collaboration with faculty in biostatistics.
 

JSimonJeff Simon, Professor
Department of Genetics, Cell Biology & Development
College of Biological Sciences

Our long-term goal is to reveal chromatin mechanisms that control gene expression during development and disease. We study the Polycomb group (PcG) transcriptional repressors, one of the premier models for investigating chromatin regulation. Our main focus is Polycomb repressive complex 2 (PRC2), an enzyme that methylates histone H3 on lysine 27 (K27). PRC2 is a fundamental chromatin-modifying machine, conserved in single-celled organisms, plants, and animals to implement gene silencing. The PRC2 output, tri-methylated H3-K27 (H3-K27me3), is a hallmark of repressed chromatin. We were one of several groups that purified PRC2, defined its composition, and revealed K27 specificity. We continue to pursue PRC2 mechanisms and H3-K27me3 consequences using in vitro biochemical assays and in vivo approaches in Drosophila; the conserved machinery yields confidence that mechanistic findings apply broadly to human biology.

YChenYue Chen, Assistant Professor
Department of Biochemistry, Molecular Biology & Biophysics
College of Biological Sciences

The Chen Lab at the University of Minnesota develops proteomics technologies to discover novel posttranslational modification pathways on histones and chromatin proteins. We also develop novel quantitative strategies to determine functionally significant signaling pathways and molecular mechanisms involved in epigenetic regulations. We are particularly interested in understanding how cell metabolism and cellular microenvironment regulate protein homeostasis and epigenetic gene expression through posttranslational modification pathways in the context of neuronal development and cancer.
 

ggeorgGunda Georg, Professor
Department of Medicinal Chemistry
College of Pharmacy

Professor Georg and her group have published over 200 scientific articles and are involved in the design, semisynthesis, total synthesis, and evaluation of biologically active agents. Current therapeutic areas include cancer, male and female non-hormonal contraception, cancer, and epilepsy. These projects require the development of synthetic methods, synthesis of natural products, and structure-activity studies aimed at improving the therapeutic efficacy of lead compounds, including natural products, and hits from high throughput screening. Interdisciplinary projects are a main focus in the Georg group, involving medicinal chemistry, biochemistry, screening, structure-based drug design, pharmacology, pharmaceutical chemistry and reproductive biology. Active collaboration exists between the Contraception Research Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, several research groups at the University of Minnesota, and around the country. Professor Georg is the PI of a NICHD U54 “Contraceptive Discovery, Development and Behavioral Research Center” that involves six institutions. She is the co-inventor of LusedraTM, which was marketed by Eisa Pharmaceuticals, of Minnelide, an anticancer agent in phase II clinical trials, and of Gamendazole, a male contraceptive agent in preclinical development.
 

nelsonHeather Hammond Nelson, Assoc. Professor
Division of Epidemiology & Community Health
School of Public Health

My research program encompasses environmental exposures and genetic traits that increase cancer susceptibility and impact patient outcomes. Our current work is focused on understanding the role of inter-individual differences in immunity, as well as viral exposures, in cancer epidemiology. In addition, I am a co-leader of the Screening, Prevention, Etiology and Cancer Survivorship program in the Masonic Cancer Center.


SLiuShujun Liu, Associate Professor
Cancer Epigenetics & Experimental Therapeutics
The Hormel Institute

Dr. Liu’s research programs focus on a translational approach to investigate the causes and the roles of receptor tyrosine kinases and epigenetics in cancer pathogenesis and drug resistance under normal physiological or obese conditions. He has authored more than 100 publications.
 
 
Pomerantz PicWill Pomerantz, Assistant Professor
Department of Chemistry
College of Science & Engineering
Epigenetic regulatory proteins control the process of heritable phenotypes beyond that which is encoded at the genomic level. Chemical probes for these proteins are in high demand for therapeutic regulation of disease and to understand new biology. Bromodomains are epigenetic protein modules that bind to acetyl groups on proteins including those of acetylated histones, helping to interpret or “read” the histone code. Since the first report of a nanomolar inhibitor of bromodomain Brd4 in 2010, 18 clinical trials have been initiated to test the efficacy of bromodomain inhibition in oncology. However, many other bromodomains lack specific chemical probes to validate their role in both health and disease. We have since applied our PrOF NMR method to three bromodomains, BrdT, BPTF, and Brd4, in several screening campaigns. As a new advance, we have started to study multiple bromodomains at once to develop selective inhibitors. See Bruker's online blog "The Resonance". Demonstrating our path, we recently discovered and synthesized the first small molecule inhibitor, which we named AU1, for BPTF to understand its role in regulating transcription. BPTF has recently been recognized as an oncogene in melanoma and colorectal cancer, and by providing a new chemical probe, we are establishing collaborative programs for studying this protein’s role in various cancers. A strong medicinal chemistry effort in our lab has now been established for improving on our leads for all three bromdomains.
 

weiLi-Na Wei, Professor
Department of Pharmacology
Medical School

Dr. Wei's lab is interested in multiple regulatory pathways and underlying mechanisms in differentiation and function of neurons and adipocytes. Two principal signaling pathways are our targets of investigation: a) hormone (vitamin A and fatty acids) signaling pathways that involve nuclear receptors and coregulators to trigger chromatin remodeling, and b) extra-nuclear signaling pathways that regulate post-transcriptional events, specifically, mRNA transport and localized translation. Our experimental systems include cultures of primary neuron, adipocyte and embryonic stem/embryonal carcinoma cells, as well as genetic animal models. Our experimental methodologies include molecular, biochemical, cellular and genetic methods, as well as heavy uses of mass spec methodologies for proteomic investigation of critical regulatory components in these signaling pathways, such as nuclear receptors, coregulator RIP140, and new RNA binding proteins. Extending from studies of these basic biological problems, we are also interested in application of these studies in important diseases such as metabolic syndromes and neurological disorders related to, or caused by, abnormal lipid metabolism, mRNA transport and/or translation in neurons.