Steven Markus, assistant professor at Colorado State University in Fort Collins, Colo., was awarded an MDA research grant totaling $300,000 over a period of three years to study alterations in the dynein gene and their effects in spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). His work to elucidate the molecular basis for dynein dysfunction in motor neuron disease could lay the foundation to identify effective, targeted therapies.
Please describe your current research.
Intracellular transport is a fundamental and critical process whereby various cargos are delivered to appropriate sites where they are needed to promote cell growth, maintenance, and division. Defects in this process compromise the survival and maintenance of several cell types, most notably motor neurons that communicate information from the brain and spinal cord to muscles throughout the body — some of which can be as long as one meter.
A critical component of the transport machinery is a family of motor proteins that carry cargos along long, polarized filaments called microtubules. One of these motors, dynein, is entirely responsible for the transport of cellular cargo such as organelles (structures inside cells) and proteins toward the cell center. Mutations in genes that encode dynein components are linked to several types of motor neuron diseases, including spinal muscular atrophy and amyotrophic lateral sclerosis. The underlying defects that give rise to these diseases are not known. This presents a significant barrier to developing effective and targeted therapeutics.
The goal of our research is to apply a set of rapid, economical, and rigorous experimental strategies to dissect the molecular basis for dynein dysfunction in various types of motor neuron diseases. In addition to providing valuable insights into the pathology of these diseases, our research will lay the necessary foundation to identify effective, targeted therapies that have the potential to alleviate symptoms in affected patients.
What inspired you to study motor neuron disease?
The devastating nature of this disease compounded by the lack of suitable therapeutic intervention initially drew my attention. However, I was especially drawn when I realized that many of the studies we do in our laboratory can be applied to better understand the underlying etiology of several types of motor neuron disease. Given the powerful yet simple tools we have at our disposal to dissect the molecular basis for mutant dynein dysfunction, it seemed foolish not to do all we could to understand these devastating diseases, and potentially make a contribution towards alleviating the suffering of those affected by them.
What is your area of focus within the motor neuron disease field?
My lab studies the mechanisms by which the molecular motor dynein is regulated to perform its myriad functions. One of these functions is to transport various cargos along motor neurons.
Given that dynein function is critical for so many cellular processes (including transport within motor neurons), it is not surprising that defects in dynein function correlate with various pathologies. Thus, a better understanding of how this motor is regulated to perform its cellular functions with precise spatial, temporal and directional precision is important for human health.
Why is it important that MDA continue to fund research in motor neuron diseases like SMA and ALS?
Funding from MDA will enable my lab to perform the research described above that is important for human health, and for potentially alleviating the suffering of innumerable patients affected by motor neuron disease. Without this funding, our work, and the critically important work from many other laboratories, would not be possible, and critical insight into the initiation and progression of motor neuron disease would be less likely to be revealed.
What do you feel people impacted by motor neuron disease can have the most hope about with respect to research right now?
The tools we have at our disposal to answer complex biological questions are becoming extremely sophisticated, and enable a detailed understanding of the mechanisms underlying motor neuron function. With an improved understanding of basic biological principles comes a clearer picture of the various diseases associated with motor neuron dysfunction. The better we understand these diseases, the better able we become at developing treatments for them.
Does your work have any potential implications for other disease fields?
Although dynein dysfunction leads to various types of motor neuron disease, defects in this molecular motor correlate with various other devastating neurological diseases, such as lissencephaly, motor and sensory neuropathy, and cortical malformation. Moreover, given the role of dynein in myriad cellular processes, it’s not surprising that dynein dysfunction also correlates with cancer. Thus, an improved understanding of this motor has important implications for improving human health.
To learn more about how MDA research is accelerating treatments and cures for SMA and ALS, please visit mda.org.
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