Adjunct Faculty - Pharmacology

Research Summary

Frank obtained his Ph.D. at the University of North Carolina at Chapel Hill with Dr. Clyde Hutchison III, where Frank's invention of oligonucleotide-directed DNA synthesis & cloning techniques and his discovery of the mammalian LINES-1 (L1) repetitive DNA was cited in Dr. Hutchison's admission to the National Academy of Sciences.Frank's postdoctoral work was with Drs. Greg Sutcliffe and Floyd Bloom at The Scripps Research Institute (TSRI) in La Jolla, California, where he invented "physiological engineering" with a cyclic AMP-elevating transgene and was co-designer of a genome-expression fingerprinting technique that led to the founding of Digital Gene Technologies, Inc., and Neurome, Inc., of San Diego. Frank's faculty research in the Department of Pharmacology included the invention of "brain circuit-testing" and the first transgenic mouse model of Obsessive Compulsive Disorder (OCD), Tourette's Syndrome (TS), and trichotillomania (TTM) -- from which Dr. Burton's model of hyperglutamatergic corticostriatal circuitry in such disorders has stimulated the clinical validation of antiglutamatergic drugs for OCD and TTM.Dr. Burton currently is a biotech, small pharma, & medtech inventor & entrepreneur who continues lecturing in our Department, maintains parallel academic affiliations with the Graduate Program in Neuroscience, The Masonic Cancer Center, and the Minnesota Supercomputer Institute, and retains a small University lab at the Minneapolis Medical Research Foundation (MMRF) in downtown Minneapolis' Hennepin County Medical Center (HCMC) to extend his academic research on: tic & compulsion circuitry & drug development cancer "bottleneck" genes supercomputer-aided design of abiogenic nucleic acids

Bio

Dr. Lange is a Professor in the Departments of Medicine and Pharmacology at the University of Minnesota. She holds the Tickle Family Land Grant Endowed Chair of Breast Cancer Research. She received her PhD from the University of Colorado School of Pharmacy in 1991. She holds memberships in the American Association for Cancer Research (AACR), The Endocrine Society (ES) and Women in Endocrinology (WE). Dr. Lange serves as teaching faculty in the U of MN Department of Pharmacology Graduate Program, the Microbiology, Immunology, and Cancer Biology (MICAB) Graduate Program, the Genetics, Cell Biology, and Development (GCD) Graduate Program, and the MSTP (MD/PhD Combined) Program. She has served on several NIH Study Sections including Biochemical Endocrinology, Metabolic Physiology, Tumor Cell Biology, and Molecular Oncogenesis. She is on the Board of Scientific Advisors to the NIEHS. Dr. Lange is the Editor-in-Chief of the journal of Endocrinology (The Endocrine Society - Oxford Academic Journals)

Research Summary

The Lange Lab is focused on the role of steroid hormone receptors (SRs) in breast and ovarian cancers. Estrogen receptor (ER) and progesterone receptors (PRs) are ligand-activated and context-dependent transcription factors that are essential for development of the breast and reproductive tract. Altered sex hormone levels contribute to cancer risk in these tissues and drive metabolic and cell fate transitions associated with rapid tumor progression. The presence of abnormally activated ERs and imbalanced/activated PR and GR isoforms in hormone-driven tumors can dramatically influence response to endocrine or other therapies. Our overarching research goal is to better understand how SR+ breast cancers and other hormone-influenced cancers of reproductive tissues escape endocrine (i.e. SR-blocking) or other molecular targeted therapies that primarily target signaling pathways that are active in proliferating cancer cells.Ongoing projects encompass the following research themes and their molecular mechanisms:• ER and PR isoform signaling cross talk in luminal breast cancer progression• Ligand-independent actions of p-SRs and p-SR-containing complexes in breast cancer• Altered SR actions in the context of ESR1 mutations or BRCA1/2 loss or mutation• Cellular "stress" sensing by phospho-GR in triple negative breast cancer progression• Fallopian tube transformation and early SR+ serous ovarian cancer progression• Cell fate plasticity (cell cycle exit/entry into G0) and breast cancer stem cell biology• Mechanisms of and biological role of cancer cell dormancy/quiescence and senescence• SR and signaling pathway regulation of breast cancer stem cell populations and biology• Breast cancer metastatic cell dissemination as circulating tumor cell/stem cell clusters

Research Summary

Neurotransmission of Pain Dr. Wilcox and colleagues are engaged in research into the spinal neurotransmission of pain and mechanisms underlying hyperalgesia, analgesia and analgesic tolerance. Studies of both excitatory and inhibitory neurotransmission in the rodent spinal cord apply behavioral, electrophysiological (both in vivo and in vitro),immunocytochemical and molecular techniques. Behavioral experiments define biologically relevant interactions, which are then examined at the cellular and molecular level using the more reductionist approaches. A key feature of research projects in this laboratory is open collaboration with laboratories located both here and at other universities. One major thrust of these investigations examines neurotransmitters thought to mediate major components of excitatory neurotransmission from primary afferent sensory fibers to secondary projection neurons in spinal cord dorsal horn: the excitatory amino acids (EAAs) like glutamate and the neurokinins like substance P. Intense or prolonged excitatory transmission via both these pathways is thought to evoke long term synaptic plasticity and excitotoxicity, which may underlie the development of some chronic pain states. A second major focus of work in the laboratory is the characterization of several inhibitory neurotransmitters and their receptors which together modulate this excitation. The neurotransmitters, enkephalin, serotonin and noradrenaline, inhibit various components of the incoming excitatory pain message in the dorsal horn via a number of inhibitory receptor subtypes. We are characterizing the interactions between these receptor subtypes and localizing them using transgenic mice, antisense oligonucleotides and immunocytochemical techniques. Finally, Dr. Wilcox facilitates access for Neuroscience students to high performance computing laboratories on campus - The Laboratory for Computational Science & Engineering and The Minnesota Supercomputer Institute (MSI). High performance computers and visualization are now finding applications in biological imaging, macromolecular modeling and neuronal simulation. A recent neuroscience graduate student developed a new method to optimize correspondence between neuronal simulations and experimental structure-function data.

Bio

I am a medical oncologist with a specialty in breast cancer. My laboratory has been interested in the regulation of cancer cells by the insulin-like growth factors (IGFs) and insulin. I also maintain an active clinical practice in the medical management of breast cancer. As part of my clinical care, I also serve as the site principal investigator on several clinical trials that employ experimental therapies targeted against IGF receptor and the PI3K pathway. I am chair in of the Agent Selection Committee of I-SPY2 and I also serve on the Executive Committee of this trial designed to validate investigational therapies in the neoadjuvant treatment of breast cancer. I have been the director of the Masonic Cancer Center since 2007. I have maintained these clinical, translational, and research activities to best identify strategies for improved outcomes in cancer.

Research Summary

Administrator Info
Name: Marina Sladojevic
Phone: 612-626-5475
Email: marinas@umn.edu
Mail: Masonic Cancer Center, University of Minnesota
420 Delaware Street SE
MMC 806
Minneapolis, MN 55455

Summary

My laboratory has been interested in the regulation of cancer cells by insulin and the insulin-like growth factors ( IGFs ). Our laboratory was one of the first to show a role for this pathway in Ewing's sarcoma and breast cancer. The laboratory remains focused on the signaling pathways regulated by the IGFs that are relevant to cancer biology. We have shown that IGF signaling is dependent on activation of specific adaptor proteins and downstream signaling molecules. Our lab is also evaluating the role for the fetal isoform of the insulin receptor (IR-A) in breast cancer biology. Interactions between estrogen receptor expressing breast cancers and insulin/IGFs result in enhanced growth and increased survival. While some anti-IGF strategies have been tested in clinical trials, toxicities and lack of targeting of IR-A has limited the clinical efficacy and the laboratory is working on strategies to target IR-A specifically without inhibition of the adult isoform of insulin receptor (IR-B).

Clinical Summary

Breast cancer