Meet the Next Generation

Posted on at October 5, 2017
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From the use of super-resolution imaging techniques to study brain synapses to the use of antisense oligonucleotides to silence genes, the new generation of HD researchers is taking the field in exciting directions. Those whose research is particularly remarkable have been invited by the HSG to attend the November 2017 HSG Annual Meeting in Colorado. Here, they will present their backgrounds, their current work, and their vision for the future of HD research.

HDSA Human Biology Fellows

Name: Amber Southwell, PhD

Education:

– BS, Biochemistry, University of Texas at Austin, Austin, TX 

– BS, Molecular Biology, University of Texas at Austin Austin, TX

– PhD, Neurobiology, California Institute of Technology, Pasadena, CA

– Postdoctoral Fellowship, University of British Columbia, Vancouver, Canada

Current position: Assistant Professor of Neuroscience, University of Central Florida, Orlando, FL

Current research interests: My research focuses on developing experimental therapies for neurodegenerative diseases, with a focus on HD. Our goal is to bring therapies from conception through to clinical translation. In addition to therapeutics, we also develop model systems and companion biomarkers to make this possible.

Reasons for interest in HD research: I became interested in therapeutic research for neurodegenerative diseases because I saw how medical science was increasing longevity, but not quality of life, due to the increasing prevalence of these intractable diseases. I focused on HD because it is the most common genetic neurodegenerative disease, allowing for genetic model system development, as well as preventative therapeutic strategies.

Hopes for the future of HD research: Like most of us, my hope is that a truly preventative therapy will be developed to protect those with the HD mutation from developing the disease. At one time, people thought about the possibility of eradicating the HD mutation through family planning, but now that we know how common new mutations are, and how many people in the general population carry a reduced penetrance allele for HD, it has become apparent that we will never eliminate the HD mutation. Now, our hope is that a positive genetic test for HD is followed by an effective, preventative treatment regimen.

Hobbies and interests: My main hobby is neuroscience, even outside of the lab. I love reading about the brain and all the cool things it can do, and all the truly weird things that go wrong when it is not working correctly. I also love cooking, dancing, SCUBA diving, and playing with my amazing kids.

Name: Daniel Wilton, PhD

Education:

– BS, Biochemistry, University of Birmingham, Birmingham, UK

– PhD, Neuroscience, University College London, London, UK

Current position: Postdoctoral fellow, Stevens Lab, F.M. Kirby Neurobiology Research Center, Boston Children’s Hospital, Boston, MA

Current research interests: My research focuses on how the nervous and immune systems interact to facilitate synapse elimination during developmental pruning windows, as well as how these processes become dysregulated in HD. In my work, I use a number of different transgenic mouse models, which parallel many aspects of disease progression in humans, and enable investigation of specific circuits through the selective elimination of mHTT from different brain regions. In conjunction with stereotactic surgeries to label specific neural connections, I use a number of super-resolution imaging techniques, including array tomography, and structured illumination microscopy, to study the role of microglia-synapse interactions in HD. In parallel, I am using a number of molecular and pharmacological approaches to dissect the signals involved in cross-talk between complement and microglia, and the mechanisms that lead to the targeting of vulnerable synapses. My ongoing studies are aimed at discerning the molecular and cellular mechanisms involved in the region-specific neurodegeneration observed in HD.

Reasons for interest in HD research: What I find compelling about HD from a research perspective is that while a great deal of extraordinary work has been done to understand the disease and the aberrant functions of mHTT, very little is known about the specific molecular mechanisms that drive the characteristic pathology in HD. It is still unclear how the ubiquitous expression of mHTT leads to the selective degeneration of specific brain regions and even circuits. The glial cells I study are the resident immune cells of the brain; therefore, my research has led me to look at the role of the immune system in HD pathogenesis. I believe this is a particularly underexplored research area, and one that is potentially very important, given that some of the earliest quantified changes in HD relate to perturbations in the immune system. 

Hopes for the future of HD research: Last year, I attended the HDSA annual conference and presented some of my current work, which gave me the opportunity to meet some of the families affected by HD, and witness the courage, generosity, and strength of this community. My own work has personally benefited from the willingness of people burdened by this terrible disease to step forward and participate in research efforts. I am very grateful for this, and I am hopeful that the work we are doing in the Stevens Lab will help to move our understanding of the disease forward, and eventually enable the development of useful therapeutics.

Hobbies and interests: I enjoy playing a number of sports, including soccer and tennis. I also enjoy learning languages, reading, and cooking. 

Name: Lisa Salazar, PhD

Education:

– BS, Biology and Chemistry (Mathematics Minor), College of Saint Mary, Omaha, NE

– PhD, Biological Sciences, University of California, Irvine, CA

Current position: Assistant Project Scientist, laboratory of Dr. Leslie Thompson, Department of Psychiatry and Human Behavior, University of California, Irvine, CA

Current research interests: I have dedicated my scientific career to understanding the molecular processes that regulate normal cellular function, and how these processes are altered in disease. These studies reach across multiple fields, including the immunological signals involved in chronic transplant rejection; fibroblast growth factor signaling in cancer; and, more recently, HD, with a focus on altered gene expression in the presence of mHTT. Through my HDSA Human Biology fellowship, I am evaluating the potential of total versus mHTT lowering to correct cellular and gene expression changes in neurons derived from HD patient stem cells. My goal is to systematically determine the specific, and potentially complex, alterations to normal neuronal function and gene expression when total HTT is reduced, as well as the differential effects of preferentially reducing mHTT compared to total HTT knockdown. A major part of this work involves the generation of iPS cell lines derived from unaffected and affected individuals that can be induced to reduce total HTT or mHTT at any point along the path from stem cells to mature neurons. These studies also include determining the effects of total HTT—lowering following treatment with ASOs or siRNA delivered using a highly effective lipid nanoparticle system. Results from these studies will further inform clinical HTT-lowering treatments.

Hopes for the future of HD research: It is an exciting time in HD research, with the advent of nucleotide-based HTT-lowering strategies holding great promise as a possible disease-modifying treatment. It is my hope that HD research will continue to identify rational therapies that modify disease progression, improving the prognosis and quality of life for HD patients and those who care about them.

Hobbies and interests: Hiking, spending time with family and friends, volunteering in therapeutic horseback riding lessons, and working to improve the lives of people with disabilities.

Shoulson Scholars

Name: Filipe Brogueira Rodrigues, MD, MSc

Education:

– MD, Faculty of University, University of Lisbon, Lisboa, Portugal

– MSc, Faculty of University, University of Lisbon, Lisboa, Portugal

Current position: Clinical Research Fellow, UCL Huntington’s Disease Centre, London, United Kingdom; Honorary Neurology Registrar, National Hospital for Neurology & Neurosurgery, London, United Kingdom

Current research interests: I am a clinical academic with a medical background, currently developing my skills and knowledge in statistics and research methodology. My areas of academic interest are research synthesis and methodology, and outcomes measures and biomarkers in HD. My field of clinical interest is neurodegeneration and neurogenetics with a special focus on HD. 

Reasons for interest in HD research: I have been clinically and academically involved with HD since 2013, when I started applying my research techniques to HD, and began to evaluate participants for the REGISTRY study in Lisbon, Portugal, under the supervision of Professor Ferreira. In 2015, I joined the UCLcHuntington’s Disease Centre led by Professor Tabrizi and Professor Bates, where I work under the supervision of Dr. Wild. My research focus has been on the systematic evaluation of new therapeutic interventions, optimization of clinical trials’ designs, and development of new outcomes measures. 

Hopes for the future of HD research: During my short, but rich, involvement with the HD community, I have grown to learn that every step regardless of its size is important in the fight against this condition. I am firmly convicted that we have never been closer to find an intervention with the power to change the course of the disease as we are today, and that there is still a lot to be done in the symptomatic intervention’s domain, where investment is needed both research- and clinically-wise.

Hobbies and interests: Sports, gastronomy, and contemporary art.

Name: Eric Keller

Education:

– Currently working on undergraduate degree, biotechnology major (animal option), biochemistry minor, Rutgers University, Newark, NJ, USA

Current position:

– Undergraduate Researcher, Samuel L. Baily Huntington’s Disease Family Service Center, Rutgers New Jersey Medical School, Newark, NJ, USA

– Undergraduate Researcher, Structural Biology Laboratory, Rutgers University, Newark, NJ, USA

Current research interests: I am currently interested in learning how the HTT aggregates transfer from cell to cell. The lab I am in is trying to figure out the mechanism that mutant HTT uses to pass into other cells. We are also interested in visualizing the many different forms of mHTT via cryo-em and 3D tomography. 

Reasons for interest in HD research: Huntington disease runs in my family, and now I possess enough knowledge to research the subject further. 

Hopes for the future: I’d like to explore the possibilities of CRISPR/Cas9 and other recent biotechnology developments, and apply them to HD research.

Hobbies and interests: I am very passionate about soccer and am a fan of the Tottenham Hotspurs. When I am not in the lab or at work, I like to play Frisbee and video games, and watch movies. 

Name: Elvina Chu, MBBS, MRCP, PhD

Education:

– BSc(Hons), Psychology University of London, England

– MBBS King’s College London GKT School of Medical Education, London, England

– MRCPsych, Maudsley training scheme, London, England

– PhD, Neuroimaging in schizophrenia, University College London, England

Current position:

Consultant Neuropsychiatrist, St. Andrew’s Healthcare, Northampton

Honorary Consultant Neuropsychiatrist, The National Hospital for Neurology and Neurosurgery, Queen Square, London, England

Current research interests: I am concerned about the lack of psychiatric support available to those with Huntington disease, especially when a more complex clinical presentation is evident. The service provided in our tertiary outpatient clinic was evaluated, and the aim will be to use this to evidence the utility of neuropsychiatry services and create a benchmark for future standards of clinical care.

Reasons for interest in HD research: In 2008, I met my first patient with Huntington disease after having been persuaded to experience an HD clinic at Queen Square by Professor Sarah Tabrizi. I was intrigued at how a disease due to one clearly defined genetic mutation could result in such varied psychiatric presentations, and I was in awe of how the families and caregivers coped.

Hopes for the future of HD research: By developing a thorough understanding of the basic science behind HD we have been able to develop novel treatment strategies that target a specific mechanism. I hope that we can extrapolate from the varied psychiatric presentations seen in HD to demonstrate and effectively treat the biological mechanisms of psychiatric disease.

Hobbies and interests: I love playing the piano and listening to classical music. I also enjoy the great outdoors and downhill skiing. This year, I finally have found the time to improve my French.

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