Andrew A. Sproul, PhD
- Assistant Professor of Pathology & Cell Biology (in the Taub Institute) at CUMC
Dr. Andrew Sproul is the founding Director of the Stem Cell and Cellular Models Platform at the Taub Institute for Research on Alzheimer's Disease and the Aging Brain, a core facility established to provide pluripotent stem cell technology as a resource for neurodegenerative and neurological disease researchers at Columbia University. His laboratory’s main focus is developing robust differentiation protocols for large-scale production of disease-relevant neurons and other CNS cell types, and using gene-editing strategies to create allelic series of isogenic disease and control pluripotent stem cell (PSC) lines. These tools will greatly aid studies of disease mechanisms and provide a better platform for therapeutic screening.
Prior to pursuing his graduate studies, Dr. Sproul trained with Sir Hans Kornberg at Boston University and helped elucidate novel fructose metabolic pathways in E. Coli. He received his PhD in Biological Sciences at Columbia University under the tutelage of Dr. Lloyd Greene, where his studies focused on regulation of the JNK signaling pathway in neuronal cell death. After a short postdoc at the Icahn School of Medicine at Mt Sinai with Dr. Sergei Sokol studying neuronal development, he worked at The New York Stem Cell Foundation for 5 years where he ran the day-to-day operations of a variety of collaborative Alzheimer's iPSC projects under Dr. Scott Noggle. Dr. Sproul started his lab at Columbia in early 2015.
Credentials & Experience
Education & Training
- PhD, 2008 Biological Sciences, Columbia University
Our goal is to develop human stem cell-derived models of Alzheimer's and other neurodegenerative diseases to aid in mechanistic studies and therapeutic development.
Our main focus is modeling the complexities of Alzheimer’s disease (AD) by using genome editing to introduce specific causal and risk mutations into human pluripotent stem cells (PSCs), thus allowing more robust cross comparisons between genotypes and the creation of allelic libraries in the same genetic background. Our first library is being constructed in the H9 human embryonic stem cell (hESC) background and our second library in the IMR90 induced pluripotent stem cell (iPSC) control backbone. We have successfully created knockin lines for multiple familial Alzheimer's disease (FAD) mutations that are available now for Taub researchers, as well as knockin late-onset Alzheimer's disease (LOAD) risk factor lines for several groups within the Taub. In addition to creating genome editing approaches, we have the capacity to generate iPSCs, including from biobanked material. Patient-specific iPSCs can be more advantageous than knockins in some cases, such as for risk factors with moderate penetrance that might require additional genetic components to manifest in the patient. We also differentiate both control and AD PSCs into disease-relevant CNS cell types such as cortical neurons, which can be further manipulated by lentiviral infection.
In terms of our own research, we are interested in both technological advances for stem cell–based cellular modeling and further mechanistic insight into AD. For example, perhaps the biggest drawback of human stem cell models is their lack of full functional maturity. Stem cell derived-cell types such as neurons are more reminiscent of the developing rather than the adult brain. For studying developmental disorders such as autism that is advantageous, but for diseases that affect the aged such Alzheimer’s disease, it becomes less optimal. In collaboration with Dr. Ottavio Arancio’s lab, we are developing novel ways to analyze non-adherent 3D cultures called cortical spheroids (hCSs) for electrophysiological function and maturation. hCSs are mixed neuronal-astrocyte cultures that are a kind of floating ‘minibrain’, and are closer to physiological conditions than monolayer culture. We are currently developing strategies to push the neurons within the spheroids into a more mature state to allow the capacity to study LTP (long-term potentiation), a critical component of memory that has not been well modeled in human PSC-derived cultures thus far. Our laboratory is also interested in elucidating novel mechanistic links between aberrant APP processing and Tau dysregulation.
Paquet D, Kwart D, Chen A, Sproul A, Jacob S, Teo S, Olsen KM, Greg A, Noggle S, Tessier-Lavigne M. (2016) Efficient introduction of specific homozygous and heterozygous mutations using CRISPR/Cas9. Nature. 533(7601):125-9. doi: 10.1038/nature17664. PMID 27120160.
Sproul, AA. (2015) Being human: The role of pluripotent stem cells in regenerative medicine and humanizing Alzheimer's disease models. Mol Aspects Med. 43-44:54-65. doi: 10.1016/j.mam.2015.06.007. PMID: 26101165.
Prè D, Nestor MW, Sproul, AA, Jacob S, Koppensteiner P, Chinchalongporn V, Zimmer M, Yamamoto A, Noggle SA, Arancio O. (2014) A time course analysis of the electrophysiological properties of neurons differentiated from human induced pluripotent stem cells (iPSCs). PLoS One. 9:e103418. PMID: 25072157.
Sproul, AA, Jacob S, Pre D, Kim, SH, Nestor MW, Navarro-Sobrino, M, Santa Maria, I, Zimmer, M, Aubrey S, Steele MW, Kahler DJ, Dranovsky A, Arancio O, Crary JF, Gandy S, Noggle SA. (2014) Characterization and Molecular Profiling of PSEN1 Familial Alzheimer's Disease iPSC-Derived Neural Progenitors. PLoS ONE 9, e84547. PMID: 24416243.
Sproul, AA, Vensand LB, Dusenberry CR, Jacob S, Vonsattel JP, Paull DJ, Shelanski ML, Crary Noggle SA. (2014) Generation of iPSC lines from archived non-cryoprotected biobanked dura mater. Acta Neuropathol Commun 2, 4. PMID: 24398250.
Nestor MW, Paull D, Jacob S, Sproul, AA, Alsaffar A, Campos BA, Noggle SA. (2013) Differentiation of serum-free embryoid bodies from human induced pluripotent stem cells into networks. Stem Cell Res.10(3):454-63. PMID: 23500645.