Many diseases that impact brain function develop during aging and affect the quality of life and our ability to live a successful healthy lifespan. These neurological diseases include Huntington’s, Alzheimer’s, and Parkinson’s. The Ellerby lab focuses on understanding the fundamental mechanisms that lead to age-related neurodegenerative diseases and identifying new therapeutic targets for these diseases. We are excited to use new technologies to interrogate why these neurological diseases are so abundant as we age and identify small molecule or protein therapeutics for these diseases. Induced pluripotent stem cells (iPSC) derived from patient cells, genomics, proteomics, small molecule screens, single cell analysis, and CRISPR/Cas9 are all technologies applied to deepen our understanding of these diseases and aging.
Why it matters
The societal burden of neurological disorders such as Alzheimer’s disease and related diseases of the brain is profound. The demographic change in the age structure of populations in developed nations has a huge impact on society and the economy. The approaches utilized in the Ellerby lab are aimed at identifying therapeutic targets and drugs and moving toward phase I clinical trials for neurological diseases.
New technologies are dramatically enhancing our ability to understand and alter the underlying causes of aging and neurodegenerative diseases. There’s a palpable sense of excitement for what is possible.
Lisa Ellerby, PhD
Dr. Ellerby grew up in the Bay Area and received her PhD in chemistry from the University of California, Santa Cruz. She carried out her postdoctoral training at the University of California, Los Angeles. During her postdoctoral training with National Academy member Dr. Joan Valentine, she studied the mechanism of superoxide dismutase and invented a novel biosensor technology published in Science. She also received an American Cancer Society fellowship for her research. Lisa Ellerby is a founding faculty member at the Buck Institute.
Dr. Ellerby has published more than 100 scientific papers and holds more than eight patents. She has served on the National Institutes of Health study group for over 15 years and also serves on review boards for numerous nonprofits, including the Huntington’s Disease Society of America, French National Research Agency, National Ataxia Foundation, and Hereditary Disease Foundation. She was an editorial board member of the Journal of Biological Sciences for 15 years and is currently an associate editor for the Journal of Huntington’s Disease. Dr. Ellerby has experience working with biotech companies and has been funded by companies such as BioMarin.
Barbara Bailus, PhD Postdoctoral Research Fellow
Dr. Bailus is a postdoctoral research fellow in the Ellerby lab. She is an expert on gene editing enzymes and Angelman syndrome. Dr. Bailus received her PhD in genetics with a double emphasis in biotechnology and translational research from the University of California, Davis. Her doctoral work focused on creating gene editing therapeutics for Angelman syndrome. During her graduate career, she was the recipient of both a National Science Foundation Fellowship and a Howard Hughes Fellowship. Her current research focuses on genetic editing for neurodegenerative diseases and understanding the regulatory pathways involved in Huntington’s disease.
Swati Naphade, PhD Postdoctoral Research Fellow
Dr. Naphade received her PhD in molecular, cellular, and developmental biology from Ohio State University. Her dissertation was focused on elucidating the role of a novel growth factor, progranulin, in spinal cord injury and neurodegenerative diseases. As a postdoctoral researcher at the University of California, San Diego, from 2013 to 2016, she studied hematopoietic stem cell therapy for the treatment of rare lysosomal disorders. She joined the Buck in April 2016. Swati’s research in the Ellerby lab focuses on Huntington’s disease (HD), stem cell modeling of disease, gene editing, and novel therapeutic targets for treatment of HD.
Stephen Scheeler PhD Candidate, USC-Buck Biology of Aging Program
Stephen is a graduate student in the USC-Buck Biology of Aging PhD program. He began his research career in Maryland while working on his bachelor’s degree in biotechnology. During that time, he studied the effects of botulinum toxin in relation to neurons derived from mouse embryonic stem cells at the Aberdeen Proving Ground. After completing his undergraduate studies, Stephen worked at the National Institute on Aging in the translational research department, where he evaluated nutritional and genetic changes in fruit flies, until beginning his PhD studies at USC. In the Ellerby lab, he has been working on projects involved in genetic manipulation of mice and stem cells in relation to neurodegenerative diseases.
Jesse Simons Research Associate
Jesse’s voyage into the field of biology began when he obtained his bachelor’s degree in biology at Chapman University in Southern California in 2014. In 2015, he entered the master’s program in biology at Dominican University of California in the Bay Area, where he interned in the Kapahi lab at the Buck Institute. His work for Dr. Kapahi included analysis of a diet-dependent effect on genes that regulate intestinal health in fruit flies, and the potential applications of this for human intestinal diseases. After successfully completing his program at Dominican, Jesse accepted a position as a Research Associate I in Dr. Ellerby's lab, working on neurodegenerative diseases. Many of his projects involve collaborations between the Ellerby lab and other labs or are focused on the potential therapeutic mechanisms of targeting specific pathways involved in neurodegenerative diseases.
Kizito-Tshitoko Tshilenge, PhD Postdoctoral Research Scholar
Dr. Kizito-Tshitoko came to the Buck from the University of Nantes, France, where he obtained his PhD in molecular biology, working on a project involving gene therapy for inherited retinal dystrophies (IRDs). Specifically, he evaluated the use of an adeno-associated virus-based nanocarrier to deliver therapeutic nucleic acids and restore visual function in large animal models of IRDs. He was drawn to the Ellerby lab as a postdoctoral scholar because he wanted to continue working on the nervous system and neurological dysfunction. His project in the lab is studying molecular mechanisms of neurodegeneration in Huntington's disease (HD) using human induced pluripotent stem cell (iPSC) derived from HD patients. Specifically, he is focused on understanding how neural stem cells derived from HD patients are altered and cause disease when they are differentiated into affected cell types such as medium spiny neurons.
R. O.Robert O’Brien, PhD
Robert O'Brien received his BS in Biological Sciences from the University of Vermont, where his undergraduate research training focused on forward and reverse genetic techniques to study the symbiotic relationship between legumes and the soil bacterium Rhizobium. He received his PhD from the University of California, San Diego, where he used mass spectrometry to study post-translational regulation of proteins in embryonic stem cells. His work in the Ellerby Lab focuses on understanding the role that post-translational modifications of the protein that causes Huntington's Disease (huntingtin) play in the toxicity of the protein. Specifically, examining interactions of caspase cleavage products of huntingtin in mouse models of HD and the role of acetylation in the turnover of huntingtin in cell culture-based models of the disease.
K. R.Karen Ring, PhD
Karen Ring received her PhD in Biomedical Sciences from the University of California, San Francisco in the laboratory of Dr. Yadong Huang. Her thesis research identified a novel way to directly reprogram mouse and human fibroblasts into induced neural stem cells. As a postdoctoral scholar in Dr. Lisa Ellerby's lab, Karen continues her passion for regenerative medicine and neuroscience by studying molecular mechanisms behind Huntington's disease (HD) using human induced pluripotent stem cell lines derived from HD patients. More specifically, Karen is interested in developing techniques to efficiently generate different types of neurons and other brain cells that are affected in Huntington's disease
N. Z.Ningzhe Zhang, PhD
Ningzhe received a Ph.D. degree from University of Rochester where he studied function and development of glial cells and their progenitors in rodent central nervous systems. After joining Dr. Ellerby’s lab at Buck in 2008, he continued the study in neuroscience with a focus on the neurodegenerative disease: Huntington’s disease (HD). He is using multiple systems, including animal models and cell models, to uncover disease mechanisms and to search for potential therapies for HD. One important part is to utilize human induced pluripotent stem cells to model the disease, make genetic correction and eventually replace cells lost in HD.
L. M.Lakshika Madushani
Lakshika Madushani attained her B.S. from UC Santa Cruz in Molecular Cell and Developmental Biology. She is currently completing her Master's in Biology from Dominican University of California and working in Dr. Ellerby's lab investigating the role of Matrix Metalloproteinases in Huntington's Disease using stem cell and mouse models.
- Miller, J. P., Holcomb, J., Al-Ramahi, I., de Haro, M., Gafni, J., Zhang, N., Kim, E., Sanhueza, M., Torcassi, C., Kwak, S., Botas, J., Hughes, R. E., Ellerby, L. M. (2010, July 29). Matrix metalloproteinases are modifiers of Huntingtin proteolysis and toxicity in Huntington’s disease. Neuron, 67(2), 199–212. Cover article.
- An, M. C., Zhang, N., Scott, G., Montoro, D., Wittkop, T., Mooney, S., Melov, S., Ellerby, L. M. (2012 Aug 3)Genetic correction of Huntington’s disease phenotypes in induced pluripotent stem cells. Cell Stem Cell, 11(2), 253–263.
- Min, S. W., Chen, X., Tracy, T. E., Li, Y., Zhou, Y., Wang, C., Shirakawa, K., Minami, S. S., Defensor, E., Mok, S. A., Sohn, P. D., Schilling, B., Cong, X., Ellerby, L., Gibson, B. W., Johnson, J., Krogan, N., Shamloo, M., Gestwicki, J., Masliah, E., Verdin, E., Gan, L. (2015 Oct). Critical role of acetylation in tau-mediated neurodegeneration and cognitive deficits. Nat. Med, 21(10), 1154–1162.
- Ring, K., An, M. C., Zhang, N., O’Brien, R. N., Gao, F., Atwood, R., Bailus, B. J., Melov, S., Mooney, S., Coppola, G., Ellerby, L. M. (2015 Dec 8). Genomic analysis reveals disruption of striatal neuronal development and therapeutic targets in a human neural stem cell model of Huntington’s disease. Stem Cell Reports, 5(6), 1023–1038.