Karen E. Hedin, Ph.D., maintains a basic science research program studying molecular mechanisms of signal transduction, with active funding by the National Institutes of Health (NIH). In particular, her lab uses state-of-the-art biochemical methods, including fluorescence resonance energy transfer (FRET), for analyzing protein-protein interactions to study G protein-coupled receptor (GPCR) and chemokine receptor signaling relevant to cancer and immune disorders.
Dr. Hedin's lab carries out cutting-edge signal transduction research involving chemokine receptors, G proteins, protein-protein interactions, Ras/MAP kinase proliferative pathways, apoptosis pathways, receptor trafficking and cell migration pathways.
Dr. Hedin has been the principal investigator of many previous years of NIH R01-funded research in the area of chemokines. She is currently investigating the molecular mechanisms and biological impact of the CXCR4 chemokine receptor in lymphocytes, cancer cells and neuronal cell types, with an emphasis on CXCR4 control of TCR signaling, T cell immune activation, regulatory T cells (Tregs) and autoimmunity.
In addition to her basic science research, Dr. Hedin has a long-standing interest in the teaching and training of young scientists, particularly those from underrepresented ethnicities and cultures. She teaches graduate pharmacology, immunology, regenerative medicine and signal transduction courses, has mentored undergraduate, predoctoral and postdoctoral researchers in her lab, serves as co-director and co-principal investigator of two R25 diversity training grants, and is the graduate program director of Mayo Graduate School's Immunology Ph.D. program.
- Understanding the central role of the CXCR4-TCR heterodimer in controlling T lymphocyte-mediated autoimmune diseases. Dr. Hedin's lab discovered the CXCR4-TCR heterodimer. Current projects include structure, function and signaling studies of CXCR4-TCR, and studies of mice in which CXCR4-TCR signaling is blocked, which causes defects in Treg number and function.
- Discovering new ways to control CXCR4's many functions throughout the body by controlling its cell-surface expression. CXCR4 is required for neuronal differentiation and for metastasis of breast, pancreas and prostate cancer. All functions of CXCR4 require its expression on the cell surface. Current projects analyze mechanisms of CXCR4 endocytosis and intracellular trafficking.
- Defining and understanding the roles of CXCR4 in hematologic neoplasms in order to identify new, effective drug targets for cancer therapy. Besides contributing to metastasis, CXCR4 critically regulates the growth and survival particularly of hematologic neoplasms in the bone marrow. Dr. Hedin's lab contributed signaling studies to one of the first detailed reports of CXCR4 in multiple myeloma. Current studies of the role of CXCR4 in acute myelogenous leukemia (AML) are defining new potential drug targets for AML and defining the role of bone marrow osteoblasts in this disease.
Significance to patient care
Dr. Hedin's research has broad significance of diseases involving immune dysregulation, cancer and leukemia. Her laboratory identifies new and more-effective drug targets connected to CXCR4 and CXCR4's regulation of cancer and immunity.
For example, the lab is now identifying drugs and signaling pathways that inhibit the protection of AML cells in the bone marrow. In vivo testing will determine if blocking this pathway will help treat mice, and eventually humans, with AML. The lab is additionally working on characterizing a powerful new drug target for treating autoimmune diseases.
- NIH Study Section ad hoc invited member, Academic Research Enhancement Award, immunology research grant reviews, 2015
- NIH Study Section ad hoc invited member, immunology research and training fellowship grant reviews, 2015
- Research paper from Dr. Hedin's lab ranked as one of the top 2 percent of published articles in biology and medicine in 2011, Faculty of 1000, 2011
- Research paper from Dr. Hedin's ranked as one of the 100 most influential G protein coupled receptor papers of 2006, Ion Channel Media Group, 2007
- NIH Study Section ad hoc invited member, Minority Biomedical Research Support (MBRS) education program grant reviews, 2007