Susan Band Horwitz (PhD ’63) receives AACR Lifetime Achievement Award

Susan Band Horwitz, Ph.D., will receive the Eighth AACR Award for Lifetime Achievement in Cancer Research. Horwitz is being recognized for pioneering research in the mechanism of the anticancer drug Taxol and for contributions to the understanding of how this microtubule-stabilizing drug arrests cell division, which eventually leads to cell death, especially of cancer cells.

Horwitz received a bachelor’s from Bryn Mawr, then came to Brandeis to do her graduate studies. According to a profile in PNAS by Tinsley H. Davis,

“At that time, there were few graduate schools that were very receptive to women,” [Horowitz] recalls. “Women were not very prominent on the faculty or in the student body.” One university stood out from the others, however. Brandeis University (Waltham, MA) had just started its graduate program in biochemistry. “Brandeis was a new and exciting place, and the people there wanted it to succeed,” says Horwitz, “yet it also had a relaxed atmosphere that was really perfect for me.”

Once at Brandeis, Horwitz worked with Nathan Kaplan, chairman of the newly formed Biochemistry Department. Her Ph.D. dissertation (1963) involved bacterial metabolism of sugar alcohols.

While juggling raising children and doing part-time postdoctoral research (some things haven’t changed so much over the years!), Horwitz became interested in pharmacology and anticancer agents. She joined the faculty at Albert Einstein College of Medicine in 1970, where she has remained since, currently serving as the Rose C. Falkenstein Professor of Cancer Research and co-chair of the department of molecular pharmacology.

Horwitz’s academic career has been vastly productive, in terms of research, publications and awards, but perhaps more significantly in terms of her research’s impact on millions of cancer patients worldwide. Her current research focuses on new natural products with similar mechanism to Taxol, looking for ways to enhance therapeutic value and to avoid drug resistance.

The AACR Award for Lifetime Achievement in Cancer Research was established in 2004 to honor an individual who has made significant fundamental contributions to cancer research, either through a single scientific discovery or a body of work. These contributions, whether they have been in research, leadership or mentorship, must have had a lasting impact on the cancer field and must have demonstrated a lifetime commitment to progress against cancer. Horwitz will receive the award at the Opening Ceremony of the AACR 102nd Annual Meeting.

New for Spring 2011: BCHM 155 Biochemistry Laboratory

This Spring, the Biochemistry Department is offering a new course, BCHM 155 Biochemistry Laboratory to be taught by Prof. Emily Westover.  This lab will meet 6 hours per week and will focus on protein biochemistry.  Students will gain skills to biochemically characterize proteins, including protein purification, enzyme kinetics, and ligand binding.  For part of each module, students will design their own experiments. Students will report their work in written and oral formats.

Spring-loading the active site of cytochrome P450

Enzymes differ from other catalysts in the exceptional substrate selectivity they exhibit.  However, the active sites of related enzymes are often very similar, even though different substrates are acted upon (for example in the superfamily of cytochrome P450s).  How does a given enzyme preferentially bind a particular substrate?  In a new paper appearing in the jounal Metallomics, Chemistry grad student Marina Dang and Profs. Susan Sondej Pochapsky and Thomas Pochapsky use nuclear magnetic resonance (NMR) to identify a helical structure remote from the active site of the enzyme cytochrome P450cam that is responsive to changes in substrate.  They propose that this helix can adjust the position of residues that contact substrate in the enzyme active site, much like the spring that holds batteries in place against electrical contacts in a flashlight.

Can a “chemical rope” help treat ALS?

In this week’s issue of PNAS, Brandeis postdoc Jared Auclair and Chemistry grad student Kristin Boggio, together with Professors Greg Petsko, Dagmar Ringe, and Jeffrey Agar discuss Strategies for stabilizing superoxide dismutase (SOD1), the protein destabilized in the most common form of familial amyotrophic lateral sclerosis. Working from the hypothesis that the mechanism of the toxicity involves dimer destabilization and dissociation as an early step in SOD1 aggregation, they looked for mechanisms to stabilize SOD1 using chemical cross-linking. Cross-linking the dimer using 2 adjacent cysteine residues results in substantial stabilization of relevant SOD1 mutants.

A "Chemical rope" stabilizes SOD1 protein. Mutations that destabilize SOD1 in motor neurons are associated with familial ALS

Read more about Prof. Agar, this research, and its potential for this technique in the treatment of ALS at Brandeis NOW

Biochemistry, Biophysics and Quantitative Biology Retreat 2010

Grad students, postdocs and faculty from the Graduate Program in Biochemistry & Biophysics and from the interdisciplinary program in Quantitative Biology gathered for their Annual Retreat October 21-22, 2010 at Marine Biological Laboratory in Woods Hole, MA. See the program here.

For ClC transporters, breaking up is hard to do

Many ion channels and transporters exist as oligomers with each subunit containing a distinct transport pathway.  A classic example is the ClC family of chloride channels and transporters that are homodimeric with a pathway for chloride permeation or chloride/proton anti-port through each subunit.  Because of their dimer structure, they have come to be known as “double-barreled shotguns” for chloride movement across the membrane.

Since each subunit appears to possess the complete machinery required for transport, it is  often wondered whether ClCs need to be dimeric in order to carry out function.  In a study published last week in Nature, Brandeis researchers Janice Robertson, Ludmila Kolmakova-Partensky and Professor Christopher Miller answer this question.  By introducing two tryptophan mutations at the dimer interface, they designed a variant of a ClC transporter that could be purified and crystallized as an isolated monomer.  With this, they were able to determine that the monomer alone was fully capable of carrying out chloride and proton transport function.  These results show that the dimer is not required and that the monomer is the fundamental unit of transport in ClCs.  The question of why ClCs evolved as dimers remains a key question for understanding membrane protein structure.

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