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.
Carlos Galicia Aguirre PhD Candidate, USC-Buck Biology of Aging Program
Carlos completed his B.S. in microbiology, molecular biology and biotechnology from the University of Idaho. His PhD work in the Ellerby lab involves studying the role of senescent cells and repetitive elements in neurodegenerative diseases. He is also interested in the implementation of machine learning methods for new ways to analyze data and find biomedical solutions. During his spare time, he likes to try foods from other cultures, watch scary movies, read and travel.
Sally Mak, PhD Administrative Lab Manager
Dr. Mak is the administrative lab manager in the Ellerby Lab with extensive molecular and biochemical studies in neurodegenerative disease, especially in Parkinson's Disease. Before joining the Buck Institute, she was a staff scientist at UC Davis, Parkinson’s Institute, and SRI International. Dr. Mak's primary job duty in the Ellerby lab is to manage the laboratory and assist in the research of her lab members.
Long McFarlin Postdoctoral Research Fellow
Long obtained her bachelor’s degree from China Pharmaceutical University, where she discovered her passion for pharmacology. Later, she joined the Pharmacology and Toxicology PhD program at the University of Kansas, where she worked on multiple projects elucidating the risk mechanisms and molecular pathology of Alzheimer’s disease. After graduation, she started her postdoctoral training at UCSF and her research focused on Parkinson’s disease and ischemic stroke. She joined Dr. Ellerby’s lab where she studies the role of cellular senescence in Alzheimer’s disease utilizing single cell genomics, in combination with induced pluripotent stem cells.
Stan Moroz Paid Intern
Stanislav Moroz is currently studying at U.C. Davis to complete his B.S. in Chemistry. Since joining the Ellerby Lab in 2018 he has assisted with projects involving the delivery of proteins through the blood brain barrier and characterizing pharmacological interventions in the Huntington’s Disease molecular pathway. Currently, he is looking into the effects of pharmacological interventions in the autophagy molecular pathway in a Huntington’s disease model.
Maria Sanchez, PhD Postdoctoral Research Scholar
Dr. Sanchez obtained her bachelor’s degree from UCLA where she was also involved in neuroscience research focused on neurodegenerative disorders. She received her PhD in Neuroscience from Uniformed Services University of Health Science. Her graduate work focused on enhancing repair mechanisms after demyelination. She joined Dr. Ellerby’s lab where she studies the underlying mechanisms contributing to neurodegeneration.
Fadzai Teramayi Dominican University Graduate Student
Fadzai Teramayi graduated from Luther College with a B.A in Biology. Prior research experiences at Luther, as well as clinical exposure assisting the elderly, encouraged Fadzai’s interest in researching therapies for treating neurodegenerative diseases. Her current research in the Benz and Ellerby lab involves proline dehydrogenase expression and its irreversible inhibition as a potential therapy for Huntington’s disease. In this research she will use mouse models as well as glial cells.
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.
Kenneth Wilson, PhD Postdoctoral Research Fellow
Kenneth received his bachelor’s degree in molecular and cell biology from University of California Berkeley, his master’s degree in biological sciences from Dominican University of California and his PhD from University of Southern California. His current research focuses on understanding how natural genetic variation can influence response to diet to affect longevity and health.
Tanimul Alam, PhD Postdoctoral Research Fellow
Dr. Tanimul Alam was a postdoctoral research fellow at the Prof. Lisa Ellerby lab. His research focused on analysis of signaling pathways in neurodegenerative disorders using iPS cells and CRISPR technologies. Previously, he worked on neural aging in C. elegans with Prof. Leonard Guarente as a postdoctoral researcher at MIT. Dr. Alam obtained his PhD at Nagoya University in Japan, where he studied neural regeneration in C. elegans. In his academic career, he received Japan Society for the Promotion of Science (JSPS) fellowship and Toyobo Biotechnology Foundation Fellowship.
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.
M. G.Melia Granath-Panelo
Melia joined the Ellerby lab as a Dominican University Master’s student in the Fall of 2019. She graduated with a degree in biochemistry from Saint Mary’s College of California, where her research focused on stem cells and regenerative medicine. In the Ellerby lab, her research utilized induced pluripotent stem cells to try to discover potential treatments for Huntington’s disease.
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
S. S.Stephen Scheeler
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 worked on projects involved in genetic manipulation of mice and stem cells in relation to neurodegenerative diseases.
J. S.Jennifer Souja
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.
- 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.
- Gafni J, Papaninikolaou T, DeGiacomo F, Holcomb J, Chen S, Menalled L, Kudwa A, Fizpatrick J, Miller S, Ramboz S, Tuunanen PI, Pehtimaki KK, Yang XW, Park L, Kwak S, Howland D, Park H, Ellerby LM. Caspase-6 Activity in a BACHD Mouse Modulates Steady-State Levels of Mutant Huntingtin Protein is Not Necessary for Production of a 586 Amino Acid Proteolytic Fragment. Neurosci. 32:7454-7465, 2012.
- 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. Highlighted in Science Translational Medicine.
- Naphade S, Embusch A, Madushani L, Ring K, Ellerby LM. Altered Expression of Matrix Metalloproteinases and their Endogenous Inhibitors in a Human Isogenic Stem Cell Model of Huntington’s Disease. Frontiers in Neuroscience, 018 Feb 5;11:736. doi: 10.3389/fnins.2017.00736. eCollection 2017.
- Naphade S, Tshilenge KT, Ellerby LM. Modeling Polyglutamine Expansion Diseases with Induced Pluripotent Stem Cells. Neurotherapeutics. Oct;16(4):979-998. doi: 10.1007/s13311-019-00810-8, 2019.
- Voisin J, Farina F, Naphade S, Fontaine M, Tshilenge KT, Galicia Aguirre C, Lopez-Ramirez A, Dancourt J, Ginisty A, Sasidharan Nair S, Lakshika Madushani K, Zhang N, Lejeune FX, Verny M, Campisi J, Ellerby LM, Neri C. FOXO3 targets are reprogrammed as Huntington’s disease neural cells and striatal neurons face senescence with p16INK4a increase. Aging Cell. Nov;19(11):e13226. doi: 10.1111/acel.13226, 2020.
- Bailus BJ, Scheeler SM, Simons J, Sanchez MA, Tshilenge KT, Creus-Muncunill J, Naphade S, Lopez-Ramirez A, Zhang N, Lakshika Madushani K, Moroz S, Loureiro A, Schreiber KH, Hausch F, Kennedy BK, Ehrlich ME, Ellerby LM. Modulating FKBP5/FKBP51 and Autophagy Lowers HTT levels, Autophagy, 2021 May 24;:1-22. doi: 10.1080/15548627.2021.1904489.
- Ehrlich ME, Ellerby, LM Neuronal Intranuclear Inclusion Disease: Polyglycine Protein is the Culprit. Neuron, 109, 1757-1760, 2021.
- Cirnaru M-D, Sicheng Song S, Tshilenge K-T, Corwin C, Mleczko J, Galicia Aguirre C, Houda Benlhabib H, Bendl J, Apontes P, Fullard JF, Creus-Muncunill J, Reyahi A, Nik AM, Carlsson P, Roussos P, Mooney SD, Ellerby LM Ehrlich ME Unbiased identification of novel transcription factors in striatal compartmentation and striosome maturation, ELife, in press.