Creating a multi-dimensional view of action in solid tumor cells
Phil Lorenzi focuses on an enzyme-drug called L-asparaginase
We got a chance to interview Dr. Phil Lorenzi of the MD Anderson Cancer Center about the work that he does expanding the usage of L-asparaginase against solid tumors.
What is the focus of your research?
We focus on an enzyme-drug called L-asparaginase and a well-characterized panel of 60 cancer cell lines called the NCI-60.
The drug, L-asparaginase, has been used since the 1960s to treat acute lymphoblastic leukemia by depleting the amino acids asparagine and glutamine, which leukemia cells cannot generate.
In our work with the NCI-60 cell lines we’ve established rationale for testing L-asparaginase against solid tumors, which could greatly expand its utility by enabling treatment of different cancer types beyond acute lymphoblastic leukemia.
We found a strong negative correlation between the anticancer activity of L-asparaginase and the expression of asparagine synthetase (ASNS; the endogenous enzyme that makes asparagine).
With collaborators, our next goal is to confirm whether that correlation holds up in patients with solid tumors (trials are underway), thereby permitting a “personalized medicine” approach to therapy with L-asparaginase.
We’re also looking for additional biomarkers of L-asparaginase activity by studying the drug’s mechanism of action. To that end, our projects are multidisciplinary, spanning the fields of pharmacogenomics, systems biology, systems pharmacology, bioinformatics, metabolomics, proteomics, cellular biology, and molecular biology. Since the drug works by depleting the amino acids asparagine and glutamine, our research has nutritional implications as well.
So you are using multidisciplinary methods to assess the mechanism of action for L-asparaginase?
Correct. No single platform has all of the answers. By integrating multiple molecular profiling data sets (e.g., protein expression and small molecule concentrations), we get a “multidimensional” view of what’s happening in cancer cells. Years ago, my mentor (Dr. John N. Weinstein) coined the term “integromics” to describe the integration of molecular profiling data from different platforms. That’s the foundation of our overall approach.
How did you first get interested in science? When did you know it would be your career?
In 7th grade (age 12), my father helped me brainstorm ideas for a science fair project. I ended up testing different metals (readily available materials from the local hardware store; nothing fancy) to see which ones yielded the best battery as measured by output to a small light bulb. I actually hated that project…but looking back, it must have sparked my interest in science. .
How did you choose Prestige antibodies®?** How do they fit into your research?
We recently screened about 14 antibodies against ASNS from a variety of vendors, and we found the Prestige antibody to be the most specific and sensitive. As we’ve adopted a “systems” approach to studying drug mechanisms of action, the number of genes/proteins we’re studying is growing quickly. Sigma’s Antibody BioGuarantee Program greatly enhances the likelihood that we’ll find an antibody that works for each of those proteins.
**Prestige Antibodies are powered by Atlas Antibodes
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