Samuel Lux, IV, MD
|Hospital Title||Chief Emeritus, Division of Oncology/Hematology|
|Academic Title||Robert A. Stranahan Professor of Pediatrics|
300 Longwood Avenue
Boston, MA 02115
Samuel Lux's research has focused on anemias, particularly spherocytosis and other membrane disorders of red blood cells. For the three decades, work in his laboratory has focused on the organization and functions of the spectrin-based membrane skeleton:
Spectrin function. Spectrin is the major protein of the membrane skeleton. Spectrins are composed of two long flexible chains (α and β) that bind side to side. Spectrins self-associate at one end, and bind to actin with the help of protein 4.1 at the other end. Dr. Lux is studying the spectrin-actin interaction because it is poorly understood. He has helped characterize the actin and protein 4.1 binding sites at the end of beta spectrin, in collaboration with a colleague, Mohandas Narla, and has found that the neighboring portion of alpha spectrin, which was previously considered inert, binds protein 4.2 in a Ca2+-dependent manner, and is necessary for actin binding. He has also discovered new interactions between proteins 4.1 and 4.2, and between the actin binding regions on alpha and beta spectrin, all of which suggests a macromolecular complex containing multiple proteins involved in actin binding and in attachment of the membrane skeleton at the far end of spectrin to the overlying lipid bilayer. Three mouse mutations with defects in the domain that have different and interesting phenotypes have recently been discovered by Dr Lux’s collaborator at The Jackson Laboratory, in Bar Harbor, Maine. They imply even more undiscovered functions.
Hereditary spherocytosis. Dr. Lux and other researchers have shown that hereditary spherocytosis (HS) is caused by defects in the connections that attach the membrane skeleton to the overlying lipid bilayer. He continues to investigate the causes of the disease and the consequences of treatments like splenectomy, particularly the possibility that splenectomy may predispose HS patients to thromboembolic disease or pulmonary hypertension.
- Resident education. Dr. Lux is collaborating with Drs Vincent Chiang, Fredrick Lovejoy and Stavroula Osganian to understand the outcomes of pediatric residents trained in different pathways at Children’s Hospital Boston in the hope of improving residency selection and training.
About Samuel Lux
Samuel E. Lux received his MD in 1967 from Kansas University School of Medicine. He completed an internship and residency at Children's Hospital in Boston and fellowships in protein chemistry at the National Institutes of Health and in hematology/oncology at Children's. He also spent two years with Harvey Lodish at the Whitehead Institute in 1985-1987 studying molecular biology.
He is the recipient of numerous honors and awards for teaching and research, including the E. Mead Johnson Award for research from the Society for Pediatric Research and American Society of Hematology's prestigious Dameshek and E. Donnall Thomas Awards for pioneering research and the Society's Mentoring Award.
Eber SW, Gonzalez JM, Lux ML, Scarpa AL, Tse WT, Dornwell M, Herbers J, Kugler W, Ozcan R, Pekrun A, Gallagher PG, Schrter W, Forget BG, Lux SE. Ankyrin 1 mutations are a major cause of dominant and recessive spherocytosis. Nat Genet 1996; 13:214-18.
Peters LL, Shivdasani RA, Liu S-C, Hanspal M, John KM, Gonzalez J, Brugnara C, Gwynn B, Mohandas N, Alper S, Orkin S, Lux SE. Anion exchanger 1 (Band 3) is required to prevent erythrocyte membrane surface loss but not to form the membrane skeleton. Cell 1996; 86: 917-927.
Peters LL. Swearingen RA. Andersen SG. Gwynn B. Lambert AJ. Li R. Lux SE. Churchill GA. Identification of quantitative trait loci that modify the severity of hereditary spherocytosis in wan, a new mouse model of band-3 deficiency. Blood 2004; 103:3233-40.
An X, Debnath G, Guo X, Liu S, Lux SE, Baines A, Gratzer W, Mohandas N. Identification and functional characterization of protein 4.1R and actin-binding sites in erythrocyte beta spectrin: regulation of the interactions by phosphatidylinositol-4,5-bisphosphate. Biochemistry 2005; 44:10681-8.
Robledo RF, Lambert AJ, Birkenmeier CS, Cirlan MV, Cirlan AF, Campagna DR, Lux SE, Peters LL. Analysis of novel sph (spherocytosis) alleles in mice reveals allele-specific loss of band 3 and adducin in alpha spectrin deficient red cells. Blood, 2010; 115:1804-14.
Stankewich MC, Gwynn B, Ardito T, Ji L, Kim J, Robledo R, Lux SE, Peters LL and Morrow JS. Targeted deletion of beta III spectrin impairs synaptogenesis and generates ataxic and seizure phenotypes. Proc Natl Acad Sci USA 2010; 107:6022-7.
Korsgren C, Peters LL, Lux SE. Protein 4.2 binds to the carboxyterminal EF-hands of erythroid alpha-spectrin in a calcium and calmodulin dependent manner. J Biol Chem 2010; 285:4757-70.
- Korsgren C, Lux SE. The carboxyterminal EF-hands of erythroid alpha-spectrin are necessary for optimal spectrin-actin binding. Blood, 2010, in press [Blood First Edition Paper, prepublished online June 28, 2010].