Dr. Lawrence and Chromosome Therapy

Dr. Lawrence and Chromosome Therapy

By Joshua Timmons, Biology, 2016

This past Monday Northeastern hosted a visit with Dr. Jeanne Lawrence, a cell biologist from the University of Massachusetts Medical School. Her talk was a part of Northeastern’s “Profiles in Innovation,” hosted by Northeastern’s president himself, Joseph Auon. During the hour-long discussion, Lawrence outlined her recently published breakthrough in chromosomal silencing, the public’s reaction to the findings, and her personal experience becoming a research scientist.

Down syndrome is a fairly common autosomal disorder that leaves those affected with 3 copies of chromosome 21. It was Lawrence and her colleagues that demonstrated they were capable of “turning off” one of the three chromosomes, restoring tested cells to their intended two copies. The basis for the science rests in a mechanism similar to that of X chromosome silencing in female sex cells, where one of the two chromosomes is completely coated in an RNA that prevents transcription. The research represents a breakthrough as they can now, by inserting an XIST gene, target “extra” chromosomes for inactivation.

Lawrence is humble with the results, and is readily willing to give credit to those that helped in the process. As she explained, growth in several other fields of research made the research possible, X chromosome epigenetics, genome editing technology, and induced pluripotent stem cells being the most notable. Yet as a result of her paper in Nature, a whole new area of research has been “broken open.” Autosomal disorders are among the most ignored in science. The predominant attitude towards them has been that there’s nothing to be done about it — but her research proves that could one day be an outdated philosophy.

However, she is hesitant when people call this a “cure”; this is preliminary research. The average human body has an estimated 40 trillion cells. That means, in people affected by Down syndrome, there are 40 trillion extra copies of chromosome 21. It’s far from feasible to “treat” all these cells; Lawrence herself says she doesn’t see it happening. Research into nanoparticles and the use of the AA virus at a retrovirus may offer treatments down the road, but it’s far from development. Additionally, Lawrence’s research has only, thus far, targeted extra chromosomes in induced pluripotent stem cells from the skin cells of people with Down syndrome. Mouse models are now being used but, as some realize, this is leagues away from human testing.

Despite the present state of the ongoing research, some people with family members impacted by Down syndrome have reacted to the research with ambivalence, if not hostility. Lawrence seemed aware of the line she must walk with her now very public research; she was quick to point out that nobody is trying to “alter” or change those affected by Down syndrome. While the ultimate goal may be the treatment of Down syndrome at an early stage in embryonic development, the research of chromosome silencing doesn’t represent the genetic altering of people who currently have the disorder.

The real next step in Lawrence’s research is to identify an effective procedure for embryonic chromosome targeting. When in development is ideal? Should just the cells most impaired by the extra chromosome be targeted or all of them in the earliest stage of development? Could treated neural stem cells be injected into the brain? These are all huge questions with complicated answers. In Lawrence’s words, “The next step will be just as large as the last one.”

A mother of three in a field still known today for its gender discrimination, Lawrence has always leaned towards the sort of research with “high risk, high reward.” She spent many of her post-doc years working towards the development of the FISH method, a procedure well known today but deemed unlikely to work when she began. Even today, in other areas of research, Lawrence has a propensity to dream big and pursue the questions that seem slightly crazy. She now has ongoing work into the supposed “junk” DNA of our genome, as she believes it may the common difference between our chromosomes that allow them continually interact on a molecular level.

While her work is astounding and her drive admirable, she was unable to answer a relatively simple question during the question-and-answer portion of the talk. A Northeastern business major asked,“How do you prepare for failure?” After pausing for a few seconds to formulate a response, she replied, “That’s a good question, I should think about that in the future” — a telling response from one the country’s most innovative researchers. Where the future of chromosome therapy is headed is unknown, but the one certainty is that it will hold profound implications for the world of autosomal disorders.

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