Maya Maor Nof, a postdoctoral research fellow at Stanford University School of Medicine in California, was awarded the 2017 SSSI-MDA Fellowship Award. The award, co-sponsored by Strength, Science & Stories of Inspiration (SSSI), will provide a total of $40,000 over two years to support Maor Nof’s work to shed light on the mechanisms underlying nerve cell death in ALS (amyotrophic lateral sclerosis).
Please describe your current research.
ALS, or amyotrophic lateral sclerosis, is a progressive fatal neurodegenerative disease that affects nerve cells in the brain and the spinal cord. ALS has a prevalence of 4-5 per 100,000 people and the risk of developing ALS increases as men and women grow older.
Certain types of nerve cells, called motor neurons, reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body. The progressive degeneration of motor neurons in ALS eventually leads to their demise. When motor neurons die, the ability of the brain to initiate and control muscle movement is lost. With voluntary muscle action progressively affected, people lose the ability to speak, eat, move and breathe. Respiratory failure is often the cause of death, and typically occurs within five years of diagnosis. Despite tremendous efforts over the last two decades, no effective therapeutics have been identified to prevent, slow, or stop neuronal death in patients.
It is becoming increasingly apparent that microtubules (MTs), which are the filaments that enable the structural support of the cell, are likely to be a critical component of this disease. Accumulating data argues that MT stability, particularly alterations in their dynamics, may be the initial driving force behind ALS. I wish to study, using mouse models, whether these alterations in microtubule stability can cause epigenetic changes (factors that influence the activity of genes but do not change the basic coding, or DNA sequence, of a gene) leading to neuronal cell death. Overall, the future findings of my proposed study may provide novel insight into the mechanisms of MTs dysfunction and cell death in this devastating human disease.
What inspired you to study ALS?
During my undergraduate studies, I read a book called “Tuesdays with Morrie.” It’s an autobiographical documentary book, written by the American writer Mitch Albom, that describes his weekly meetings each Tuesday with Morrie, his former college professor who was diagnosed with ALS. This book gave me a perspective on ALS, sharing an intimate description of the thoughts of someone as his body deteriorated, and inspired me to study the mechanism of this devastating disease.
What is your focus in the field of ALS research?
I am focusing on the dysfunction of microtubules. These are tubular structures inside the cell that play an important role in various process. They maintain the structure of the cell, provide a platform for intracellular transport and are involved in secretory vesicles, organelles and intracellular macromolecular assemblies.
Why is your focus important?
As many of the processes in which microtubules play an important role are also disrupted in ALS, this makes me believe that microtubules are indeed the driving force initiating the disease. This notion is also supported by recent findings revealing that mutation to a microtubule gene is sufficient to cause a familial form of ALS.
What is the expected outcome of this research?
I hope that by studying the disruption of the microtubules and looking at the neuronal gene expression profile changes, I will be able to better understand the molecular pathways that may cause this disease.
How will your research lead to treatments and cures?
My goal is to gain a better understanding of the changes in gene expression as a result of microtubule dysfunction, which may form the basis of this disease. In the long term, an understanding of this gene expression regulation program will advance the current knowledge about ALS and potentially may help spur novel therapeutic strategies.
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