As the 25th anniversary of the identification of the genetic expansion responsible for HD approaches, a new generation of HD researchers is emerging. Scientists, investigators, and clinicians from diverse professional backgrounds have come together to apply their expertise to the study of HD biology and therapeutic development. HD Insights interviewed six of these next-generation HD researchers who have been invited by the Huntington Study Group (HSG) to attend the 2015 HSG annual meeting. We bring you their backgrounds, their current work, and their vision for the future of HD research in this edition.
They come from all over the world, bringing experience in nursing, engineering, mathematics, and the biological sciences. Their research has been recognized as particularly promising by the HD research community. Three of them represent the inaugural group of HSG Shoulson Scholars, recognized as outstanding junior investigators with promising futures in HD research. The others are among those recognized by the Huntington’s Disease Society of America (HDSA) as HD Human Biology Project Fellows. The HDSA HD Human Biology Project was launched in 2013 to fund research that advances understanding of the biology of HD in human patients.
Together with the winners of the second annual HD Insights of the Year competition, these individuals represent the promise of future HD research and therapeutic development. We hope that the brief profiles presented here will be the first of many opportunities they will have to share their excellent work and their service to the HD research community.
Next Generation Scholars at HSG 2015
2015 Shoulson Scholars
Kelly Andrzejewski, DO, PhD, Nancy Downing, PhD, RN, SANE-A George McNally, BMedSci 2013
HDSA HD Human Biology Project Fellows
Helen Budworth, DPhil Tanya Garcia, PhD Jun Hua, PhD
NAME: Kelly L. Andrzejewski, DO, PhD
EDUCATION: BS, Biology, Canisius College, Buffalo, NY; DO, Michigan State University College of Osteopathic Medicine, East Lansing, MI; PhD, Michigan State University, East Lansing, MI
CURRENT POSITION: Experimental Therapeutics in Movement Disorders Fellow, University of Rochester Medical Center, Rochester, NY
HOBBIES: Spending time with family and friends
RESEARCH INTERESTS: Dr. Andrzejewski conducted her PhD research on a mouse model of Parkinson disease, which sparked her interest in pursuing training as a movement disorders specialist. She completed her neurology residency at University Hospitals Case Medical Center in Cleveland, OH, and then joined the Experimental Therapeutics fellowship program at the University of Rochester. Her clinical experience with HD patients during her fellowship led her to focus her research on assessing the feasibility of measuring HD motor symptoms using wearable sensors and smartphone technologies. After completing her movement disorders fellowship in June 2016, she plans to practice as a movement disorders specialist and HD clinical trial investigator. She is also interested in further investigating the role of the cannabinoid system in HD pathophysiology and exploring other potential therapies for HD.
HOPES FOR THE FUTURE: Dr. Andrzejewski hopes that the next ten years will bring new treatments to slow or halt the progression of HD. She told HD Insights, “We all know that research takes a long time, and that we need groups of investigators such as those that make up the Huntington Study Group to help develop new treatments for HD.”
PUBLICATION HIGHLIGHT: Andrzejewski K, Gwin J, Harris DA et al. Sensor-based remote measurement of the motor symptoms of Huntington’s disease. [abstract] To be presented during the Ninth Annual Huntington Disease Clinical Research Symposium, October 24, 2015, Tampa, FL.
NAME: Nancy R. Downing, PhD, RN, SANE-A
EDUCATION: BSN, RN, and PhD, College of Nursing, University of Iowa, Iowa City, IA; postdoctoral research with Janet Williams, PhD, RN, FAAN, and Jane Paulsen, PhD
CURRENT POSITION: Assistant Professor, College of Nursing, Carver College of Medicine
Department of Psychiatry, University of Iowa
HOBBIES: Bicycling, including the 15,000-person RAGBRAI Ride across Iowa
RESEARCH INTERESTS: Dr. Downing’s research focuses on improving quality of life and caregiver experiences for individuals with HD, those at-risk for HD, and their families. She describes these measures as “palliative,” emphasizing that despite the tendency to conflate this with end-of-life care, these measures are aimed at improving quality of life and functioning throughout the disease course.
She is currently developing patient-reported outcome measures that can better measure quality of life for HD patients and their caregivers, as well as investigating the ways in which HD gene carriers and their families conceptualize and cope with the gradual loss of function in HD. Through her work identifying lifestyle-based interventions, Dr. Downing hopes to elucidate low-risk ways for individuals at risk for HD, and those living with the disease, to improve their functioning. As a geneticist, she is interested in the effects of these interventions on epigenetic modifications that may affect HD progression.
HOPES FOR THE FUTURE: Dr. Downing hopes that the next ten years will bring the development of gene-based therapeutics that can modify disease course. She hopes that lifestyle-based adjuvants to biological therapies identified through large-scale studies, such as diet changes, physical exercise, and mental exercises, will become mainstream and help to improve patients’ and families’ quality of life.
PUBLICATION HIGHLIGHT: Downing NR, Kim JI, Williams JK, et al. WHODAS 2.0 in prodromal Huntington disease: measures of functioning in neuropsychiatric disease. Eur J Hum Genet. 2014 Aug;22(8):958-63.
NAME: George McNally, BMedSci
EDUCATION: BMedSci, Psychological Medicine, University of Birmingham, Birmingham, England
CURRENT POSITION: Final-year medical student, University of Birmingham
HOBBIES: Playing sports, including field hockey, skiing, golf, and tennis
RESEARCH INTERESTS: Mr. McNally became interested in neuropsychiatric rating scales used in HD through his research mentor, Dr. Hugh Rickards. His work has focused on exploring the validity of the Problem Behaviors Assessment (PBA), developed by Dr. David Craufurd, using novel analytical methods. His research has led to a collaboration with Dr. Craufurd to further develop seven apathy items into a potential PBA subscale. This is Mr. McNally’s first foray into research, and he plans to continue his work in HD research when he finishes his medical training and moves into clinical practice.
HOPES FOR THE FUTURE: Mr. McNally hopes that efforts to modernize and refine rating scales and other assessment tools will help improve the detection of important symptom changes in HD clinical trials, and especially inform trials of novel disease-modifying therapies.
NAME: Helen Budworth, DPhil
EDUCATION: BS, Genetics and Microbiology, University of Liverpool, Liverpool, England; DPhil in Biochemistry, Wolfson College, University of Oxford, Oxford, England; post-doctoral research at the Lawrence Berkeley National Laboratory, Berkeley, CA
CURRENT POSITION: Biochemist Research Scientist, Lawrence Berkeley National Laboratory
HOBBIES: Surfing and enjoying the beautiful beaches of California
RESEARCH INTERESTS: Dr. Budworth has devoted her career to studying mechanisms of DNA repair in human disease and exposure to harmful agents. She joined Dr. Cynthia McMurray’s lab in 2011, applying her knowledge of DNA repair mechanisms to the study of HD. In 2013, Dr. Budworth was awarded an HDSA HD Human Biology Award to study transcriptomic and metabolomic biomarkers of HD progression in humans. Her work has led to a collaboration with Dr. Christopher Ross at Johns Hopkins University, in which blood samples from individuals with HD and control patients are analyzed for their transcript and metabolite patterns. They then correlate the metabolite profiles of plasma from patients with the gene expression differences observed in genes that control metabolic processing. The work holds promise for producing robust biomarkers of HD progression.
HOPES FOR THE FUTURE: Dr. Budworth told HD Insights, “We are on the cusp of breakthroughs for much more effective treatments for HD. Gene therapy, and the evolution of more gene editing tools, will hopefully be of great benefit to HD patients, in whom the monallelic single gene mutation is a very good target for gene therapy. Our lab has identified the role of somatic expansion in the onset of disease, that is, further expansion of the polyglutamine repeat in patients, in addition to what they inherit. This opens the door for new therapeutic options − by slowing down or blocking somatic expansion, we can delay the onset of disease. This is a very exciting avenue for therapeutics.”
PUBLICATION HIGHLIGHT: Budworth H, Harris FR, Williams P, et al. Suppression of somatic expansion delays the onset of pathophysiology in a mouse model of Huntington’s disease. PLoS Genet. 2015 Aug 6;11(8):e1005267. doi: 10.1371/journal.pgen.1005267. eCollection 2015.
NAME: Tanya Garcia, PhD
EDUCATION: BS, Mathematics, University of California, Irvine, CA; MS, Industrial Engineering and Operations Research, University of California, Berkeley, CA; MSc, Statistics, University of Western Ontario, London, ON, Canada; PhD, Statistics, Texas A&M University, College Station, TX
CURRENT POSITION: Assistant Professor of Biostatistics, School of Public Health, Texas A&M University
HOBBIES: Traveling, hiking, and exploring the outdoors with her husband and two rescued dogs
RESEARCH INTERESTS: Dr. Garcia’s work focuses on the development of statistical models to predict HD progression. Using data from previous observational studies such as PREDICT and COHORT, she and her colleagues are developing an advanced statistical model of patient-specific features of HD progression. The model aims to be able to predict not only when events occur in the progression of the disease, but also how long it takes those events to occur in time. The applications of the model could be far-reaching. In particular, Dr. Garcia and colleagues hope to be able to better predict and design clinical trials by using the model to inform power calculations and effect sizes needed in trial design of the trials.
HOPES FOR THE FUTURE: “We are close to finding out which different biomarkers are really associated with disease onset,” Dr. Garcia told HD Insights. “We hope we will have very reliable, targetable biomarkers in 10 years, and that our developing statistical methods will help with this process.”
PUBLICATION HIGHLIGHT: Wang Y, Garcia TP, Ma Y. Nonparametric estimation for censored mixture data with application to the cooperative Huntington’s observational research trial. J Am Stat Assoc. 2012;107(500):1324-1338.
NAME: Jun Hua, PhD
EDUCATION: BS, Electrical Engineering, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China; MS, Precision Instruments, Shanghai Jiao Tong University,
Shanghai, People’s Republic of China; MSE, Biomedical Engineering, and PhD, Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD
CURRENT POSITION: Assistant Professor and Research Scientist, F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD; Assistant Professor, Russell H. Morgan Department of Radiology, Johns Hopkins University
HOBBIES: Spending time with his two young children, skiing and snowboarding, playing various sports and traveling with family
RESEARCH INTERESTS: Dr. Hua specializes in the development and application of advanced MRI technologies to the study of human neurological diseases. Dr. Hua’s research collaboration with Dr. Christopher Ross has revealed increased blood volume in small arteries and arterioles in the brains of prodromal HD patients, before brain atrophy can be observed. His current research is focused on the use of novel functional and physiological MRI techniques to develop early functional biomarkers of HD progression based on neurovascular and metabolic changes in the brain. He emphasizes the importance of HD as a model disease that can shed light on the mechanisms of other neurodegenerative diseases.
HOPES FOR THE FUTURE: Dr. Hua hopes to see improvements in functional biomarkers, which have historically been difficult to develop due to the small effect sizes and difficulty in detecting these biomarkers with current methods. He is particularly interested in new technological developments that will enable more accurate and specific biomarker detection.
PUBLICATION HIGHLIGHT: Hua J, Unschuld PG, Margolis RL, et al. Elevated arteriolar cerebral blood volume in prodromal Huntington’s disease patients. Mov Disord. 2014 Mar;29(3):396-401. doi: 10.1002/mds.25591. Epub 2013 Jul 11.