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. 

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.

Professor Georg and her group have published over 240 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 with several research groups at the University of Minnesota, and around the country. Professor Georg is the PI of an NICHD P50 center: “Contraceptive Discovery, Development and Behavioral Research Center” that involves six institutions. The Georg group is interested in discovering selective inhibitors for bromodomain proteins with a special emphasis on discovering selective inhibitors for BRDT for male contraception.

Dr. Guan's research focuses on statistical analysis and methodology development related to epigenome-wide association studies.  His lab aims to identify novel epigenetic markers and mechanism underlying complex diseases and risk factors.

Dr. Hammond Nelson's 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.

The Jain Lab’s overarching goal is to combine classical biochemistry with genomic and proteomic approaches to decipher fundamental principles of chromatin engagement by epigenetic machinery and determine how they contribute to human biology and disease. In particular, we study how the Histone Code is laid down and how chromatin is accessed in vitro and in vivo, enabling us to understand how the regulation of these processes affects vital cellular mechanisms such as transcription, splicing, and DNA damage response. Our work aims to broaden the fundamental understanding of epigenetic regulation in human health and lead to new therapeutic approaches in cancer.

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.

My role in the proposed project is that of PI. I have been studying the pathobiology of chronic pain and analgesic pharmacology for over 25 years since my PhD training in Neuroscience. As a post-doctoral trainee at the Oregon Health and Sciences University, I was the first recipient of the John J. Bonica Post-Doctoral Training Fellowship from the International Association for the Study of Pain. After working in both biotechnology and academia, I joined the Faculty at McGill University in 2007 where I was promoted to Associate Professor in 2013. I joined the Department of Anesthesiology, University of Minnesota, as a Full Professor in June 2020. I have 7 patents, have received research funding from both NIH and the Canadian Institutes for Health Research (CIHR), have co-authored over 80 manuscripts and was awarded the Early Career Award from the American Pain Society. I have served as a peer reviewer for NIH, CIHR, NSF, Medical Research Council (UK), as well as private and non-profit organizations. I have expertise in chronic pain, neuronal plasticity, epigenetics, neuropharmacology, and immunohistochemistry and in human studies involving participants with chronic pain.

 Of greatest relevance to the UMN Epigenetics Consortium is my published and preliminary work on the role of DNA Methylation in chronic pain. Of note, we have demonstrated that i) epigenetic control of the sparc gene in human and rodent intervertebral discs is associated with chronic low back pain, ii) chronic pain following nerve injury in rodents is associated with wide-spread and changes in DNA methylation in the frontal cortex and in T cells, iii) neuropathic pain-related cortical changes in methylation can be reversed by SAMe and physical exercise (both of these treatments attenuate behavioral signs of pain in animal models, iv) there is a DNA methylation signature in the T cells of humans with chronic LBP vs. controls, v) DNA methylation is reprogrammed in degenerating intervertebral discs obtained from back pain patients vs. controls and finally, vi) prenatal stress is associated with altered DNA methylation machinery and increased pain responses following nerve injury in subsequent adults.