SUMMARY
Emanuel E. Strehler, Ph.D., studies Ca2+ transport and Ca2+ signaling in normal cell function and disease. The long-term goal of this research is to understand the molecular mechanisms underlying cellular Ca2+ handling and the consequences of failure of proper Ca2+ regulation in the development of disease.
Dr. Strehler's research focuses on the calcium pumps in the plasma membrane. These pumps are essential for the setting of cellular Ca2+ levels and are involved in calcium transport in the intestine and kidney, as well as in neuronal function. The lack or inappropriate function of these pumps has been linked to multiple clinical disorders, including age-related hearing loss, cardiovascular disease and Alzheimer's disease, among others.
Collaborative studies performed in Dr. Strehler's laboratory use a range of techniques, including those of recombinant DNA technology (PCR, mutagenesis and vector construction) and cell biology (confocal fluorescence microscopy and cell imaging) to study the basic mechanisms of calcium pump targeting and function in cultured cells.
Biochemical methods, such as protein expression, protein-protein interaction analysis and Ca2+ uptake measurements, are also used and will be combined with physiological experiments (epithelial Ca2+ transport) in collaborative studies with several groups at Mayo Clinic and internationally to determine the role of calcium pumps in dietary calcium uptake.
Dr. Strehler's research has been funded in the past by the National Institute of General Medical Sciences (NIGMS) and the National Institute of Neurological Disorders and Stroke (NINDS).
Focus areas
- How are calcium pumps directed to different locations in the cell membrane, and how do they affect local calcium signaling? Dr. Strehler's team is developing genetically engineered calcium sensors that will enable quantitative measurements of local Ca2+ signals affected by calcium pumps in different membrane locations, such as the apical or basal/lateral membrane of intestinal and kidney epithelial cells.
Dr. Strehler also uses fluorescence-labeled recombinant calcium pumps to better understand the "address signals" that allow different calcium pumps to be delivered to distinct cellular destinations.
- How do the plasma membrane calcium pumps contribute to calcium uptake in the intestine, and what is their role in vitamin D3 regulation of dietary calcium regulation? Using mice as a model system, Dr. Strehler is interested in defining the contribution of the two major calcium pumps in intestinal calcium absorption, how these pumps are regulated by vitamin D, and how defects in one or both of the pumps may affect whole-body calcium regulation.
- How is the calcium-sensor protein CALML3 linked to cell differentiation, migration, and adhesion in wound healing and cancer? Dr. Strehler is also interested in characterizing targets of the Ca2+ sensor protein CALML3, which may play a role in cell adhesion and migration.
By learning more about the partners of CALML3, such as the motor protein Myosin-X, the laboratory hopes to gain insights into how Ca2+ and CALML3 regulate cell migration during normal wound healing, and why loss of CALML3 is consistently observed in epithelial cancers.
Significance to patient care
Calcium pumps are needed in different membrane compartments, such as at neuronal synapses, in the stereocilia of cochlear hair cells or in the basolateral membrane of intestinal epithelial cells.
Dr. Strehler's research will help unravel how these pumps are delivered to the proper place in the cell and how their Ca2+ pumping function affects processes, such as resetting Ca2+ levels in cochlear hair cells or Ca2+ absorption in the gut.
These studies help us understand and eventually fight diseases associated with defects in local calcium transport, such as hearing loss and neuronal degeneration, or insufficient dietary calcium absorption contributing to osteoporosis.
Professional highlights
- Editorial Board, Current Chemical Biology, 2010-present
- Editorial Board, World Journal of Biological Chemistry, 2009-present
- Editorial Board, The Journal of Biological Chemistry, 2006-present
- Program Director, Molecular Neuroscience track, Mayo Graduate School, 2000-2007
- Associate Program Director, Biochemistry and Molecular Biology track, Mayo Graduate School, 2012-present