Five Questions with Researcher Johanna Hamel

Johanna Hamel

Johanna Hamel, a neurologist at the University of Rochester in New York, was awarded a clinical research training fellowship for her work in comparative studies of RNA toxicity in myotonic dystrophy (DM). The two-year award, co-sponsored by the American Academy of Neurology and the American Brain Foundation, will provide a total of $130,000, including a $10,000-per-year stipend for tuition, to support Hamel’s work to shed light on the molecular processes that drive DM.

Please describe your current research.

Current theories hold that the genetic defect underlying myotonic dystrophy (an abnormally expanded section of DNA, called a repeat expansion or, simply, repeat) results in toxic RNA, which accumulates in the nucleus of the cell where it traps proteins important for normal cell function. However, this may not be the complete explanation, as it has been observed that the extent of proteins trapped does not correlate with the severity of patient symptoms.

I will compare how the extent of toxic RNA accumulation and protein dysfunction in the muscle cell nucleus relates to signs and symptoms of patients. My focus will be mostly on type 2 myotonic dystrophy (DM2), but what we learn studying DM2 will in turn increase our knowledge about type 1 (DM1).

I will be focusing specifically on the relationship between repeat length and effects of toxic RNA, and where there might be mismatches. For example, we generally think that the longer the repeat, the more toxic the RNA, the bigger the problems. However, while in DM2 the repeat lengths are usually much longer than in DM1 and there seems to be more toxic RNA accumulating, DM2 is a milder disease. Understanding this discrepancy might shed light on other mechanisms involved in causing the disease.

What inspired you to study DM?

I first met patients with myotonic dystrophy as a medical student, and eventually those early experiences led to my decision to choose neurology, and many years later, a career in neuromuscular medicine. I have always been interested in multi-systemic diseases involving not only the peripheral, but also the central nervous system, such as myotonic dystrophy.

What is your focus in the field of DM research and why is it important?

I am studying the mechanism through which the genetic defect causes symptoms and signs in myotonic dystrophy and am interested in developing biomarkers.

Therapy approaches for myotonic dystrophy are based on our current partial understanding of the cause of the disease. Learning more about how the disease is caused in muscle may not only guide current development of therapies but also provide more insight about the disease mechanism in other tissue.

How will your research lead to treatments and cures?

Current therapies under investigation for the treatment of myotonic dystrophy are designed to decrease the levels of toxic RNA and thereby release trapped proteins. A better understanding of how and to what extent the RNA is toxic for the cell will help to define therapeutic targets for further drug development. This knowledge about RNA toxicity may also be of use for other genetic disorders caused by toxic RNAs.

What do you feel people impacted by DM can have the most hope about with respect to research right now?

Treatments are currently being developed and tested for myotonic dystrophy type 1, as well as biomarkers to monitor efficacy of these treatments. Our goal is to extend this work to myotonic dystrophy type 2.

Does your work have any potential implications for other disease fields?

There are several other genetic diseases caused by toxic RNAs similar to myotonic dystrophy. Some of these diseases are within the field of neuromuscular medicine, while others primarily affect different organ systems.A better understanding about RNA toxicity will likely be of use in all these disorders.

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