October 2011

Member update

Yale’s Horwich wins Lasker award,
one of science’s top honors

Member_Update_Horwich_Arthur_smArthur L. Horwich, Sterling professor of genetics and professor of pediatrics at the Yale School of Medicine, was named co-winner of the prestigious 2011 Albert Lasker Basic Medical Research Award for discovering the class of cellular machines that controls the folding of newly manufactured proteins into their biologically active structures. Along with his co-winner, Franz-Ulrich Hartl of the Max Planck Institute of Biochemistry in Germany, Horwich determined that these machines, dubbed “chaperonins” because of their assisting role, capture non-native proteins in an open ring via exposed hydrophobic surfaces and then release them into an encapsulated hydrophilic chamber, where they can fold in isolation without the possibility of aggregation. This work began in 1987, when members from Horwich’s laboratory accidentally came across a protein-folding function in mitochondria during a genetic screen in yeast. The work has clinical implications in a set of human neurodegenerative disorders, such as Lou Gehrig’s and Alzheimer’s diseases, in which misfolded proteins form insoluble clumps in cells.

Rosenberg wins genetics society’s leadership award

Member_Update_RosenbergLeon E. Rosenberg, an expert in inherited metabolic disorders in children, won the American Society of Human Genetics 2011 McKusick Leadership Award. “He and his colleagues discovered that children with a potentially lethal disorder of organic acid metabolism suffer from defective metabolism of vitamin B12. They then went on to demonstrate that supplements of B12 were remarkably beneficial clinically,” the genetics society said in a statement announcing the award. “Furthermore, Rosenberg’s work has also provided crucial insights into the basic mechanism by which proteins synthesized in the cytoplasm are transported into mitochondria. In this work, the X-linked disorder ornithine transcarbamylase deficiency was critical.” Rosenberg is a professor at the department of molecular biology and at the Woodrow Wilson School of Public and International Affairs at Princeton University. He is studying the recent history of the medical research enterprise. He is examining the role of the key players – government, academia, industry, foundations, independent institutes and voluntary health agencies – and the policy issues that face them. He also is interested in the role of the physician-scientist in the medical research community. Rosenberg serves as an adjunct professor of genetics at Yale University School of Medicine, where he spent more than two decades as a researcher, teacher and administrator. Rosenberg is a member of the National Academy of Sciences and a fellow of the American Academy of Arts and Sciences, the American Association for the Advancement of Science and the Institute of Medicine. In the 1990s, Rosenberg was the chief scientific officer at Bristol-Myers Squibb Co. and the president of the Bristol-Myers Squibb Pharmaceutical Research Institute.

Thomas Steitz honored with fellowship from Royal Society 

Member_Update_Steitz_ThomasThomas A. Steitz, Sterling professor of molecular biophysics and biochemistry and professor of chemistry at Yale University and a Howard Hughes Medical Institute investigator, was one of eight foreign scientists named as fellows of the Royal Society, the United Kingdom’s national academy of science. The honor recognizes exceptional contributions to science. Steitz, the co-winner of the 2009 Nobel Prize in chemistry, was selected for his contributions to establishing the structures and mechanisms of the proteins and nucleic acids involved in gene expression, replication and recombination. Steitz and his colleagues at Yale determined the atomic structure of the 50S ribosomal subunit as well as the complexes the subunit forms with substrate, intermediate and product analogues. The researchers also have looked at complexes of the 50S ribosomal subunit with more than a dozen antibiotics. From those analyses, Steitz’s laboratory found that the ribosome is a ribozyme, understood the mechanism of peptide bond formation and demonstrated how several types of antibiotics function. The work has led to the creation of new antibiotics now in clinical trials. Future research directions for the Steitz research group include establishing the atomic structures of the ribosome captured in the act of protein synthesis in each of its conformational states with various factors as well as interacting with the proteins involved in protein secretion.

Joan Steitz wins cancer research achievement award 

Member_Update_Steitz_JoanJoan A. Steitz, Sterling professor of molecular biophysics and biochemistry at Yale University and a Howard Hughes Medical Institute investigator, won the Robert J. and Claire Pasarow Foundation’s 2011 Annual Medical Research Award for Extraordinary Achievement in Cancer Research. The award is presented to increase public awareness of vital areas of investigation. Steitz is well known for the discovery and understanding of the function of small nuclear ribonucleoproteins (snRNPs, pronounced “snurps”). snRNPs occur only in vertebrate cells and don’t have any genetic coding functions. Instead, they play a critical role in splicing pre-messenger RNA in the nucleus. snRNPs cut out introns from pre-mRNA and splice together the resulting segments to produce mature messenger RNA. Several aspects of Steitz’s research have implications for cancer research. Her laboratory has been interested in the role of viral noncoding RNAs in instigating various cancer types, such as Karposi sarcoma. Steitz’s work on snRNPs also may provide novel insights into the diagnosis and treatment of lupus, an autoimmune disease that develops when patients make antibodies against their own DNA, snRNPs or ribosomes.

Seidman wins prize in cardiovascular science from Ohio State 

Member_News_SeidmanChristine E. Seidman, professor of genetics and medicine at Harvard Medical School and Howard Hughes Medical Institute investigator, was awarded the Jay and Jeanie Schottenstein prize in cardiovascular science from Ohio State University. This prize is awarded biennially to an international leader in the clinical sciences of cardiovascular medicine, cardiothoracic surgery or the basic sciences of molecular or cellular cardiology. Seidman, who is also the director of the Cardiovascular Genetics Center at Brigham and Women’s Hospital, received the award for her research on gene mutations that cause heart disease. The main focus of her work is on cardiovascular conditions such as cardiomyopathy, heart failure and congenital heart malformations using molecular biology tools such as high-throughput nucleic-acid sequencing methodologies. Her laboratory also produces model organisms that carry human mutations and uses these models to determine how responses to gene mutations perturb or influence myocardial structure and specialized heart functions. In 2009, Seidman and colleagues published a paper in Nature Genetics that explored the genetic basis for blue baby syndrome, in which babies are born with malformed hearts that are unable to properly oxygenate blood.

Guengerich’s work in toxicology, cancer honored with prize

Member_Update_guengerich_frederickF. Peter Guengerich, the interim chairman of Vanderbilt University’s biochemistry department and an associate editor for the Journal of Biological Chemistry, last month won the American Chemical Society Division of Chemical Toxicology Founders’ Award. The prize acknowledged his many contributions to chemical toxicology. “This means a lot to me in that I have worked in this area since I was a postdoc,” Guengerich said in a statement. “I am grateful that I have had so many opportunities to contribute – and so much just plain fun doing the research and training others.” Guengerich has spent the past three decades pursuing a better understanding of how P450 enzymes metabolize drugs and carcinogens and how carcinogens interact with DNA to form adducts and how adducts produce genetic mutations. Guengerich’s laboratory uses a number of methodologies to understand the catalytic functions of human P450 enzymes, such as site-directed and random mutagenesis, kinetic analysis, and substrate-activity relationships.  The laboratory is also pursuing the identification of reactions catalyzed by “orphan” human and bacterial P450s whose functions have not yet been characterized. Guengerich, one of the most highly cited researchers worldwide in the areas of biochemistry and pharmacology, has been a faculty member at Vanderbilt since 1975 and has served as director of the Center in Molecular Toxicology there since 1981.



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