Currents

LSI Faculty Win Exceptional Honors

In May David Ginsburg was elected a Member of National Academy of Sciences. Election to the Academy is considered one of the highest honors bestowed upon scientists across all scientific disciplines in recognition of distinguished and continuing achievements in original research. LSI Professor Rowena Matthews is also a member.

Xian-Zhong Shawn Xu was named U-M's only Pew Scholar in June. The Pew names only 20 awards to America's most promising scholars. The Pew program invests in early to mid-career scientists, seeks to expand foundation of biomedical knowledge & advance scientific frontiers. As a Pew Scholar, each scientist will receive a $240,000 award over four years to help support his or her research, as well as gain inclusion into a unique community of scientists that encourages collaboration and exchange of ideas.

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Awards

Andrea Baines in the Ginsburg Lab will be awarded the Rackham Predoctoral Fellowship for the upcoming year.

Christopher G. Evans who is a 2nd year graduate student in the Gestwicki group and the Chemical Biology PhD Program was awarded a Cellular Biotechnology Training Program (CBTP) Fellowship.

Huan Tang (Mike) Li in the Garneau-Tsodikova lab won a spot in the Cellular Biotechnology Training Program.

David Ginsburg received the Distinguished Career Award as part of the "13th Biennial Awards for Contributions to Hemostasis" at the XXI Congress of the International Society on Thrombosis and Hemostasis in Geneva Switzerland, July, 2007.

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LSI Symposia & Events

Weizmann Institute/LSI Research Partnership was held in April. LSI hosted 10 scientists from our sister institute in Rehovot, Israel, for three days of scientific exchange which included an all-day symposium and individual meeting with potential U-M collaborators. Over 100 faculty and students joined the Weizmann delegation for an interactive lunch in the LSI lobby.

The Michigan Symposium on Genomic Biology was held April 16 in the Biomedical Sciences Research Building Auditorium featuring talks by eight renowned researchers from around the world. The symposium was organized and hosted by LSI faculty Anuj Kumar.

In May, LSI held its sixth annual scientific symposium was "Frontiers in Stem Cell Biology." A roster of world-leaders in stem cell biology presented their cutting-edge research with plenty of time for interaction with UM researchers and students. Harvard's Dr. Stuart Orkin gave the Mary Sue and Kenneth Coleman Life Sciences Lecture entitled "Control of stem cells."

Structural Enzymology: A Symposium Honoring Rowena E. Matthews, was held in May and is traditional for a faculty member who will be retiring. The two day celebration recognized Rowena's contributions to science, particularly in the field of Biological Chemistry, and brought together scientists from all over the country. It was cosponsored with University of Michigan Department of Biological Chemistry, Biophysics Research Division, and the Life Sciences Institute.

The LS-CAT Sector 21 Dedication Ceremony in May opened the beamline at the Argonne National laboratory outside Chicago. Spearheaded by the late Martha Ludwig, the new beamline is a collaboration between LSI and researchers from the University of Michigan, and many other institutions including Michigan State University, Wayne State University, Van Andel Institute, Northwestern University, the University of Illinois, University of Wisconsin and Vanderbilt University. LS-CAT or the Life Sciences Collaborative Access Team is a consortium of academic and research institutions engaged in cutting-edge structural research with X-radiation to solve 3-D structures. Gabby Rudenko, Janet Smith, Jeanne Stuckey, John Tesmer, and Zhaohui Xu of LSI and the Center for Structural Biology are the primary users of the facility in the LSI.

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PhD Defenses

Ju Huang from Dan Klionsky's lab defended June 4. "Studies of the molecular components of autophagy and the sorting mechanism of the multivesicular body pathway in Saccharomyces cerevisiae." Ju will be doing a postdoc with Dr. John Brumell at the Hospital for Sick Children in Toronto, Canada.

Abigail (Abby) Fahim from the David Ginsburg lab defended her thesis on May 15, 2007. "Directed Evolution and In Vivo Function of Plasminogen Activator Inhibitor-1". Abby has been accepted as a transfer student to Baylor College of Medicine in Houston, Texas and will be starting clinical rotations in July toward completion of her MD.

Chung-Han Lee from the Kun-Liang Guan lab defended June 4, 2007. "Glucose Starvation Induces Apoptosis of TSC-/- cells in a p53-dependent Manner."

Brian A. Moore from Zhaohui Xu's lab. "Structures of Exocyst subunit Exo70 from Yeast and Mouse." Dr. Moore will be a postdoc at Harvard with Allen Steere. Angela Fleischhaker from Rowena Matthews' Lab defended in May. "Governing conformation in cobalamin-dependent methionine synthase: Probing the roles of the axial cobalt ligands."

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Of Note

The ISI Web of Knowledge has calculated an impact factor of 6.71 for Autophagy —Daniel Klionsky is Editor-in-Chief. This is a higher factor than some of the journals considered to be competitors including Molecular Microbiology (5.63), Journal of Biological Chemistry (5.81), Journal of Cell Science (6.43), Molecular Biology of the Cell (6.56) and Traffic (6.61).

Jordan Shavit, of the Ginsburg lab M.D., Ph.D., will give a presentation at the XXIst Congress of the ISTH 2007 Meeting in Ge- neva, Switzerland, July, 2007. "Regulation of Plasma von Willebrand Factor (VWF) by Modifier Genes".

LSI was featured in an article published by the American Diabetes Association regarding "Potential Weight-Regulating Gene Identified" by Emma Hitt excerpted here: A gene called T-box 15 (TBX15) may be involved in regulating body fat amount. Carey Lumeng, MD, PhD, with the University of Michigan Life Sciences Institute, who moderated the session on obesity during which the presentation was made, suggested that the function of TBX15 will have to be carefully explored. "Studies in mice indicate that TBX15 may have widespread functions and may impact multiple tissues such as bone and skeletal development," he told Medscape. "It will also be interesting to determine whether TBX15 also correlates with markers of insulin resistance."

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Top discoveries Include...

Yukiko Yamashita's laboratory published research discussing asymmetrical division of adult stem cells showing that adult stem cells often divide to produce one self-renewed stem cell and one differentiating cell, thus maintaining both populations. (Science, January 2007)

A team led by Jiandie Lin discovered how metabolic pathways work in concert with the circadian clock to create the predictable daily patterns of energy storage or usage. By creating genetically altered "knockout" mice, they uncovered a new job for an old protein called PGC-1α (alpha), a master regulator of genes that control energy pro- duction in the cell. (Nature, May 2007)

Jason E. Gestwicki and Daniel J. Klionsky discussed potential therapeutic applications of autophagy recognized to be involved in various developmental processes and various diseases including cancer and neurodegeneration. (Nature Reviews, Drug Discovery, April 2007)

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Selected Publications

Drug Targets in Mycobacterial Sulfur Metabolism. Bhave D, Muse WB, Carroll KS. Infectious Disorders - Drug Targets 7:140-158, 2007.

Covalent CouN7 enzyme intermediate for acyl group shuttling in aminocoumarin biosynthesis. Balibar CJ, Garneau-Tsodikova S, Walsh CT. Chem Biol. 14: 679-90, 2007.

Rescue of Degradation-prone mutants of the FK506-rapamycin binding (FRB) protein with chemical ligands. Stankunas K, Bayle JH, Havranek JJ, Wandless TJ, Baker D, Crabtree GR, Gestwicki JE. Chembiochem 9:1162-9, 2007.

Potential therapeutic applications of autophagy. Rubinsztein DC, Gestwicki JE, Murphy LO, Klionsky DJ. Nat Rev Drug Discov 6:304-12, 2007.

Fatal hemorrhage in mice lacking gamma-glutamyl carboxylase. Zhu A, Sun H, Raymond RM Jr, Furie BC, Furie B, Bronstein M, Kaufman RJ, Westrick R, Ginsburg D. Blood 109:5270-5, 2007.

Genetic regulation of plasma von Willebrand factor levels: quantitative trait loci analysis in a mouse model. Lemmerhirt HL, Broman KW, Shavit JA, Ginsburg D. J Thromb Haemost 5:329-35, 2007.

Genome-wide mapping of DNase hypersensitive sites using massively parallel signature sequencing (MPSS). Crawford GE, Holt IE, Whittle J, Webb BD, Tai D, Davis S, Margulies EH, Chen Y, Bernat JA, Ginsburg D, Zhou D, Luo S, Vasicek TJ, Daly MJ, Wolfsberg TG, Collins FS. Genome Res 16:123-31, 2006.

Dauer. Hu PJ, WormBook, ed. The C. elegans Research Community, WormBook, doi/10.1895/wormbook.1.144.1, www.wormbook.org, 2007.

Distant conserved sequences flanking endothelial-specific promoters contain tissue-specific DNase-hypersensitive sites and over-represented motifs. Bernat JA, Crawford GE, Ogurtsov AY, Collins FS, Ginsburg D, Kondrashov AS. Hum Mol Genet 15:2098-105, 2006.

Metabolic derangement of methionine and folate metabolism in mice deficient in methionine synthase reductase. Elmore CL, Wu X, Leclerc D, Watson ED, Bottiglieri T, Krupenko NI, Krupenko SA, Cross JC, Rozen R, Gravel RA, Matthews RG. Mol Genet Metab 91:85-97, 2007.

Global aggregation of newly translated proteins in an Escherichia coli strain deficient of the chaperonin GroEL. Chapman E, Farr GW, Usaite R, Furtak K, Fenton WA, Chaudhuri TK, Hondorp ER, Matthews RG, Wolf SG, Yates JR, Pypaert M, Horwich AL. Proc Natl Acad Sci U S A 103:15800-5, 2006.

Genetic diversity and population structure inferred from the partially duplicated genome of domesticated carp, Cyprinus carpio L. David L, Rosenberg NA, Lavi U, Feldman MW, Hillel J. Genet Sel Evol 39:319-40, 2007.

The probability distribution under a population divergence model of the number of genetic founding lineages of a population or species. Jakobsson M, Rosenberg NA. Theor Popul Biol 71:502-23, 2007.

Dimerization and DNA-Binding Properties of the Transcription Factor DeltaFosB.Helena J. M. M. Jorissen, Paula G. Ulery, Lisa Henry, Sreekrishna Gourneni, Eric J. Nestler, and G. Rudenko. (Biochemistry, April 2007)

Gapex-5, a Guanine Nucleotide Exchange Factor for Rab5 that Regulates Glut4 Trafficking in Adipocytes. Lodhi, I.J., Chiang, S-H, Chang, L. Inoue, M., Vollenweider, D., Watson, R.T., Pessin, J.E. and. Saltiel, A.R. (Cell Metabolism 2007)

Bone marrow-specific Cap gene deletion protects against high-fat diet-induced insulin resistance. Lesniewski, L.A., S.E. Hosch, J.G. Neels,C. de Luca, M. Pashmforoush, C.N. Lumeng, S.H. Chiang, M. Scadeng, A.R. Saltiel and J.M. Olefsky. (Nature Medicine, April 2007)

Activation of RalA Is Required for Insulin-Stimulated Glut4 Trafficking to the Plasma Membrane via the Exocyst and the Motor Protein Myo1c. Chen, X.C., Leto,D., Chiang, S.H., Wang, Q. and Saltiel. A. R. (Developmental Cell, September 2007)

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