Research Spotlight: John LaCava, The Role of Mobile Genetic Elements in Cancer

Ami Defesche

At Iris.ai, we believe that excellent research should be in front of as many eyes as possible. Iris.ai Community members are striving every day to discover, innovate and solve some of the world’s most pressing challenges. So, in this new feature from the Iris.ai Community, we spotlight new, ongoing and established research directly from our community members.

While this is a showcase of their work, we also welcome discussion, questions, and feedback in the comments section or our facebook group. So, with this spirit of collaboration and celebration in mind, I’d like to present our very first Research Spotlight: John LaCava from Rockefeller University.

The Role of Mobile Genetic Elements in Cancer

John LaCava John LaCava is a Molecular Life Scientist and Research Assistant Professor at The Rockefeller University in New York City and is currently in the data collection phase of his research on the role of mobile genetic elements in cancer.

The Research

When asked to describe his work in more detail, John said:

“L1 retrotransposons are parasitic genes within human DNA and innate mutagens known to be active in the majority of cancers. These ancient parasitic genes are locked into a kind of evolutionary arms race with their hosts, in this case, us; our cells have evolved ways to try to keep them inactive. However, when activated, for example when a healthy cell transitions into a cancerous one, retrotransposons can hop to new locations in the genome by ‘copy and paste.’ So, the original copy of the gene (DNA) remains where it is, but an RNA produced from the gene will go on to be reverse transcribed into a new piece of DNA, and the new copy of the gene will be inserted elsewhere in the genome. An important motivating factor in my research is that L1 expression in cancer correlates with worse patient outcomes.

A set of 80-100 L1 sequences are still mobile and capable of inducing disease in any given individual. Although L1 is thought to be repressed in most somatic cells, retrotransposition is demonstrable in most epithelial tumors, making it a “hallmark of cancer.” Accumulating evidence suggests that L1 contributes to cancer via effects on gene expression and DNA damage. However, other mechanisms may also be relevant: proteins that are present in the cell will interact with L1 RNA. In some cases these proteins constitute the cell’s defenses against L1 — their purpose is to destroy the RNA. In other cases the L1, being a parasite, is able to appropriate proteins from their typical roles in the healthy homeostasis of the cell and repurpose them. This dysregulation can exacerbate disease. There appears to be a fundamentally reciprocal linkage between cancer development and L1 activity: cancer makes a favorable environment for L1 expression, and L1 expression exacerbates cancer development. This linkage is, therefore, an important target for cancer research.”

In the simplest terms, John studies the struggle between a selfish gene and the cells that host it. Like a terrible roommate you’re stuck with; how to limit your own stress? You probably take sweet revenge when you can, but, the emotional scars persist. And, sticking with sketchy analogies, imagine that you get some new neighbors who like to party too much – and they get on with your roommate like a house on fire – turning your living situation into an even bigger nightmare characterized by chronic anxiety and alarm. Well, that’s L1 and cancer. It’s hard to make light of cancer – but where disease is concerned, excessive worry is already abundant, so a little levity goes a long way.

Regarding the future application of this work, John aims to discover and characterize the contributions of protein-protein interactions to L1 molecular biology and the role of L1 in cancer evolution. He says, “Although our work is focussed on elucidating the relationships between L1 and cancer – and holds potential for diagnostic, prognostic, and/or therapeutic clinical value – we face a secondary challenge related to a lack of methods and technology applicable for our purposes. Therefore, on the one hand, we hope to solve the negative impact of L1 on human health, and on the other hand, we develop and provide generalized solutions for studying protein interactions in cancer.”

The Researcher

John’s inspiration to pursue this subject came from an interest in the challenges of analyzing and characterizing difficult and exotic phenomena in human molecular cell biology, and in translating basic research tools into clinical applications. “LINE-1 retrotransposons pose such challenges and have emerging clinical importance; and frankly, I simply find them fascinating for all of their intricacies and remaining secrets,” he says.

And, when his research concludes? John plans to continue his work in cancer research but will move, more generally, into cancer and human disease interactome research.

“I believe that protein interactions will increasingly become valid druggable targets, vastly expanding our ability to provide therapies and cures, once we have developed sufficient understanding of how their networks form and behave – which likely remains yet many years away. I am also interested in harnessing retrotransposons as synthetic genome engineering tools, perhaps complementing, or surpassing, what today is generating excitement in the form of CRISPR/Cas.”

Interested in connecting with John? Connect with him via e-mail, LinkedIn, Facebook or Research Gate below.

lacava@gmail.com
www.linkedin.com/in/jlacava
www.researchgate.net/profile/John_LaCava
https://www.facebook.com/soundsofscience.net/
https://www.facebook.com/b13logy/

Thank you, John, for sharing your impactful work with us, and the Iris.ai Community!

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