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MicroRNAs: A New Approach to Cancer

  • Title: Assistant Professor of Pediatrics, Johns Hopkins University
  • Education: PhD, Johns Hopkins University, 2001
  • Recommended by: Aravinda Chakravarti

Joshua Mendell began his career studying post-translational regulatory path-ways called nonsense-mediated RNA decay. But during his graduate work in the late 1990s, he became increasingly fascinated by some of the initial data coming out of the labs of microRNA pioneers such as Victor Ambros and Dave Bartel. “I became interested in the field at its early stage when some of the original phenotypes were studied in C. elegans that were due to loss of function of microRNAs,” says Mendell. “But what got me excited was the possibility that human microRNAs might regulate similar pathways, which we know to be important in cancer pathogenesis.”

When Mendell started his own laboratory about three and half years ago, he was really interested in exploring a possible connection between microRNAs and cancer biology. Currently, he and his colleagues are focused on understanding how microRNAs participate in some of the most important and well known cancer pathways, including those that control classic oncogene tumor suppressors such as Myc and p53. “People have been covering Myc for a long time and it has been known to control literally thousands of protein coding genes in the genome,” says Mendell. “But until recently, it was not appreciated that part of the tumorigenic program initiated by the Myc oncogene could also involve microRNAs.”

So about three years ago, Mendell and his team started developing array-based technologies capable of globally monitoring microRNA expression. What they discovered was that Myc does indeed control microRNA expression and that microRNAs controlled by Myc play an important role in tumorigenesis.

Despite the progress being made in the microRNA field, the costs associated with cutting-edge sequencing technology are still a big roadblock to speeding up the discovery process. “One thing that is not quite as accessible as I would like is some of the very newest high-throughput sequencing methods on a price scale where it could really be used on a daily basis,” Mendell says. “For the kind of research that we do, that technology is really very enabling and powerful, and can really be used to characterize expression in lots of states, so I hope that that is going to happen.”

Mendell could also use some help with tools to improve research with animal models. At the moment, researchers are limited by transfection, making the introduction of microRNAs to animal cells a major challenge. Specifically, any kind of method that would enable the delivery of small RNAs in vivo systemically to animals would be a tremendous benefit for his research, he says.

Looking ahead

Mendell says that the prospect of developing cancer therapeutics is a definite end goal of his research. Right now, his lab concentrates on refining animal models for evaluating the potential for developing microRNAs for therapeutics. “In our work, we have seen that expressing microRNAs in cancer cells can have very profound anti-tumorigenic effects,” he says. “I hope that we’re able to elucidate pathways that are downstream for the specific microRNAs that we’re most interested in, what they regulate, how they work, and why they have these very potent phenotypes in cells.”

Publications of note

In June of 2007, Mendell and his colleagues published a paper in Molecular Cell entitled “Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis.” In it they asked whether microRNAs are important in the function of p53, and found that one particular microRNA called mir34A plays a crucial role in the ability of p53 to kill cells through apoptosis.

And the Nobel goes to…

Mendell says that he would like to be awarded the Nobel Prize for developing microRNAs as potent anti-cancer therapies that could really affect patients’ lives.

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