The HD Human Biology Project allows HDSA to foster innovative patient-focused research to help the HD community better understand the biology of HD as it occurs in people. There is nothing more exciting or more relevant to HD than scientific observations made in people with the disease”. – George Yohrling, PhD, Senior Director, Mission and Scientific Affairs at HDSA.
Meet Dr. Amber Southwell an HD researcher who was recently awarded HDSA HD Human Biology Project Fellowship. Read about what drew Dr. Southwell to the field of HD research, her passion for her work and how the support of the HD community is critical to advance important research.
Grant support from the HDSA has been invaluable in my search to transition from a postdoctoral position to an independent faculty position. As someone training in Canada, I am not eligible for the transitional funding mechanisms in the United States. The competition for research focused faculty positions at top tier universities in the US is extremely high, and many excellent researchers are overlooked if they do not have independent funding. Support from the HDSA is allowing me to break through this barrier and will be instrumental in establishing my own research group focused on HD.
As governmental research funding becomes more limited, it is extremely important to have non-governmental funding avenues, such as the HD Human Biology Project Fellowship, available to young researchers. Additionally, it is very compelling for researchers when those who are personally affected by HD share their stories and experiences. Every scientist wants to feel that the work they do really matters, and interacting directly with members of the HD community can provide inspiration and focus to young researchers.
In my undergraduate studies at the University of Texas at Austin, I became fascinated with the brain. I realized that with the advancing median age of our population, neurodegenerative diseases will be an increasingly difficult societal burden and decided to focus my efforts on therapeutic development for these intractable diseases. During my doctoral training with Paul Patterson at the California Institute of Technology, I focused my studies on HD because it is inherited. I reasoned that HD always being caused by the same genetic mutation would simplify preclinical studies and allow for preventative therapies. By the time I realized how complex HD is, despite the simple genetics, I was completely immersed and will continue in this course of study until there is no need for it.
The HD research field is extremely collaborative. In my view, we are all on the same team and HD is the only adversary. We are also fortunate to work with a committed, informed, and involved patient, family, and caregiver community. I work with and interact with a broad variety of people touched in different ways by HD. This provides unique perspectives and incredible motivation for my research.
For me, the biggest struggle is the translational timeline for experimental therapeutics. With huntingtin lowering therapies, for the first time, we are now able to prevent the onset of HD in mice and to reverse symptoms once they’ve begun. This has been such an exciting time, and has sparked such a sense of urgency. It is difficult to temper this excitement with the realities of drug development. Mice, while providing enormous insight, are not people, and there are many important and necessary hurdles to cross in safely moving an experimental therapy from mice to men.
I’ve been extremely lucky to have many wonderful mentors, but I think the two that stand out the most are Paul Patterson and Michael Hayden. Paul was my doctoral mentor, and he put me on the path of HD research. He encouraged me through an ambitious project, letting me find my own way, while being there if and when I asked for help. Paul helped teach me to think, to question, and to write as a scientist. Michael is my postdoctoral mentor, and he has helped me to extend my focus beyond my own bench. Michael has helped teach me to mentor, to lead, and to develop an extensive collaborative network. Combining the lessons from these two very different, exceptional men has shaped me profoundly as a scientist and as a person.
We have developed a method called IP-FCM for quantifying levels of the mutant huntingtin protein, the direct cause of HD. IP-FCM is sensitive enough for use in HD patient cerebrospinal fluid, the fluid that bathes the brain. Using an experimental therapy that reduces mutant huntingtin in the brain and IP-FCM in HD mice, we demonstrated that lowering mutant huntingtin in the brain results in a similar reduction of the protein in cerebrospinal fluid. Considering that several huntingtin lowering therapies are in development with one currently in clinical trials, having a method to measure changes in the levels of mutant huntingtin in the brain is critical. Through my HDSA Human Biology Project Fellowship, we will use IP-FCM to determine how mutant huntingtin protein in cerebrospinal fluid changes over time in individuals and will develop a companion method that will allow us to compare levels of mutant and normal huntingtin protein. While the huntingtin lowering therapy that is currently in clinical trials causes reduction of both mutant and normal huntingtin, others in development are specific to only the mutant protein. Thus, it will be important to measure and differentiate both proteins to effectively evaluate these therapies.
My project could provide biomarkers for use in clinical trials allowing clinicians to better evaluate new therapies for efficacy in reducing levels of the toxic mutant huntingtin protein in the brain. Huntingtin lowering therapies are the most targeted and specific interventions for HD with the potential to improve or even prevent all of the many symptoms of HD. Having reliable and accurate methods to evaluate these exciting new therapeutics will be critical in moving them from the lab to the clinic.
The vast majority of my time is happily spent in the lab or with my family. However, before having children, I enjoyed scuba diving and swing dancing, which I did professionally for a time. In fact, my husband and I connected when he was my swing dancing student.