Two more NSF GRFP fellowship winners

Brandeis had 1 current undergraduate, 7 undergraduate alunmi, and 1 incoming graduate student win NSF graduate research fellowships this year. In addition to those cited below, Richard Stefan Isaac ’10 and Orly Wapinski ’09 were also selected. Isaac graduated magna cum laude with a BS/MS degree with high honors in Biochemistry. His thesis work “Functional Characterization of Regulators of Bacterial Pathogenicity and
” was done in the Petsko/Ringe lab. His work teaching in the Biology laboratory also resulted in a paper  in CBE Life Science Education. Isaac is currently a graduate student at Univ. of California, San Francisco. Wapinsky received a BS degree with Highest Honors in Biology, doing in her thesis work “Characterization of Interferon Regulatory Factor-4 mutants” with Professor Ruibao Ren. Wapinski is currently studying at Stanford.

Biochemistry Senior Research Talks

It’s also the season for Senior Honors / Masters Thesis talks…


Annual Senior Research Talks
2009/2010 Biochemistry Honors and BS/MS Candidates

Friday, April  23, 11:30-1:30pm – G-zang 122

Clarence Friedman – BS/MS

Characterization of 1-d-deoxyxylulose reductoisomerase
Advisor: Dan Oprian

Stefan Isaac  – BS/MS

Functional Characterization and in silico Modeling of HlyU
Advisors:  Dagmar Ringe/Greg Petsko

Seth Lieblich BS/MS

Bacterial Gene Repressors
Advisor: Dagmar Ringe

Miranda Patton BS/MS

Mutation of the Active Site of IMP Dehydrogenase, to Find a Novel Mutant and Create a Hybrid GMP Reductase
Advisor:  Liz Hedstrom

Nat Lazar BS

We are superfamily: bioinformatic and biochemical analyses of protein evolution
Advisor:  Douglas Theobald

Kanchana Ravichandran BS

Formation of heterotetramers between the human isozymes of Inosine 5’-Monophosphate Dehydrogenase
Advisor:  Liz Hedstrom

Seth Robey BS

Streamlining C1C-0 Purification and Examining the pH Dependence of an Amino Acid Transporter
Advisor:  Chris Miller

Kenta Yamamoto BS

The Type-1 Insulin-Like Growth Factor in Cancer and Hematopoiesis
Advisor: Ruibao Ren

Everyone is welcome and encouraged to come.  Pizza will be provided.

PhD Defense Season

It’s the season for PhD defenses…

  • Apr 20: Megan Zahniser (Biochemistry), On the structure of Benzaldehyde Dehydrogenase, a Class 3 Aldehyde Dehydrogenase from Pseudomonas putida – 2pm, Rosenstiel Penthouse
  • Apr 21: Chris Hoefler (Biochemistry/Bioorganic Chemistry). Inhibitors of IMPDH: Tools for Probing Mechanism and Function – 3:40 pm, Gerstenzang 122
  • Apr 22: Tepring Piquado (Neuroscience), Language and the aging brain – Thu 4/22/2010, 2 pm, Volen 201
  • Apr 23: Suvi Jain (Molecular and Cell Biology), Regulation of DNA Double-Strand Break Repair by the Recombination Execution Checkpoint in Saccharomyces cerevisiae – 3:30 pm, Rosenstiel 118
  • Apr 29: Ben Cuiffo (Molecular and Cell Biology), Targeting RAS palmitoylation in hematological malignancies – 2 pm, Abelson 131

Post-translational modifications of Ras Oncogenes

Ras oncogenes were first discovered almost 40 years ago, when scientists experimenting with what would later be known as retroviruses found that virus taken from a leukemic rat could induce sarcomas in other rodents.  Today we know that activating mutations of human RAS are present in ~30% of all human cancers, including both solid tumors of nearly every tissue type as well as hematological malignancies.  But despite decades of study and a wealth of knowledge collected about RAS family proteins as well as their upstream activators and downstream signaling effectors, targeting oncogenic RAS has remained elusive.

Recently, much effort had been focused on developing RAS farnesyltransferase inhibitors, which target an essential post-translational modifying enzyme which adds a farnesyl-lipid necessary for membrane anchoring to RAS, which is normally tethered to the inner face of the plasma membrane.  However, these inhibitors have not been effective as hoped, as a geranylgeranyl-lipid can be alternatively added  by another enzyme when farnesyltransferase is inhibited.  Targeting both enzymes subsequently proved to be too toxic to normal cells.

A recent paper in Blood by Ben Cuiffo, a Molecular and Cell Biology graduate student, and Prof. Ruibao Ren, sets the sights on another post-translational modification: palmitoylation.  Palmitoylation serves as a second membrane anchor for some RAS isoforms, allowing them entry to the secretory pathway to traffic from the Golgi to the plasma membrane.  The necessity for palmitoylation for oncogenic transformation was previously unclear as RAS signaling scenarios from the Golgi have been characterized in a variety of cell types in culture.  Cuiffo and Ren made use of a mouse leukemia model driven by oncogenic N-RAS to drive leukemogenesis in vivo. They found that a point mutation that prevents palmitoylation but does not affect RAS activation was unable to drive leukemogenesis in this model.  The finding that palmitoylation is essential for N-RAS leukemogenesis in vivo exposes a potentially powerful new cancer target, not only for N-RAS driven leukemias, but for a variety of malignancies that rely on N-RAS to transduce oncogenic signals.

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