Sigma BioBlogs

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

AACR is over 100 years old, with a membership of 30,000+.  The membership is quite inclusive, with a mixture of people from basic science research, clinical research, and also physicians, patients, survivors, and patient advocates all intent on studying and learning more about how to stop cancer.

We got the chance to meet many of them, and a few answered the question “Where does your bio begin? (You can still enter your video too!).

Communication, collaboration, research and education are all a part of AACR’s mission, with 6 Cancer journals for the thousands of scientist who are members, and also CR magazine, to provide information directly relevant for cancer patients, survivors, and patient advocates.

For AACR 2010, the volcanic ash prevented many European presenters from attending, so AACR shifted and met the need by patching the speakers through via video and teleconference.  Some of the recorded talks are here.

Plus an amazing twitter feed which is still active 4 days post-meeting as bloggers sift through their notes and communicate the information that they gathered during the meeting.

The science has come a long way too.  Many traditional topics were under exploration, such as studies around Ras and p53,  there  were also discussions about newer technologies for  such as microRNAs, using biomarkers for early detection,  nanotechnology, and systems biology.

Some blogs of note:

Sally Church’s blog. This lady knows the cancer community.  I got the chance to have coffee with her and she knew half the researchers walking in and out of the conference hall.

Nature writer Brian Maher has a series of short blogs about the sessions he attended.

Another look at Bert Vogelstein’s talk…

This AACR video details some fascinating statistics on cancer research