HiF-Seq™ platform enables high efficiency single cell sequencing and is particularly well-suited for frozen tissue sections from post-mortem brain tissue which have been challenging for conventional single cell sequencing technologies.

Using this proprietary technology, we are creating the world’s largest repository of data from high-quality, clinically characterized brain tissues of patients with neurodegenerative diseases including Alzheimer’s and Parkinson’s. With this approach, we can study  genomic information for individual cells.

In parallel, we are developing automation systems for sample processing, including sample and library preparation for single cell sequencing which provides scalability at high accuracy and low cost.

As the repository of data derived from the HiF-snRNAseq™ platform continues to grow, it will be increasingly valuable for guiding development of diagnostic assays and therapeutics. We have already discovered a significant list of novel biomarkers and therapeutic targets.

 

Elucidating critical disease pathways, biomarkers and targets with unprecedented resolution to inform development of new therapeutics and diagnostics.

 

HiF-Seq™ Platform

 

Analysis

 

 
 

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Ko, H.S., Y. Lee, J.-H. Shin, S.S. Karuppagounder, B.S. Gadad, A.J. Koleske, O. Pletnikova, J.C. Troncoso, V.L. Dawson*, T.M. Dawson. Phosphorylation by the c-Abl Protein Tyrosine Kinase Inhibits Parkin’s Ubiquitination and Protective Function.” Proc. Natl. Acad. Sci. U.S.A., published ahead of print September 7, 2010, doi:10.1073/pnas.1006083107; 107:16691-16696 (2010) PMID: 20823226, PMCID: PMC2944759.

Shin, J.-H., H.S. Ko, H.C. Kang, Y. Lee, Y.-I. Lee, O. Pletinkova, J.C. Troncoso, V.L. Dawson* and T.M. Dawso*. “PARIS (ZNF746) Repression of PGC-1α Contributes to Neurodegeneration in Parkinson’s Disease.” Cell, 144:689-702 (2011), PMID: 21376232, PMCID: PMC3063894.

 

Lee, Y., S.S. Karuppagounder, J.-H. Shin, Y.-I. Lee. H.S. Ko, D. Swing, B.D. Lee. H.C. Kang, L. Tessarollo, V.L. Dawson and T.M. Dawson, “Parthanatos Mediates AIMP2 Activated Age Dependent Dopaminergic Neuronal Loss.” Nature Neuroscience, 16:1392-1400 (2013). PMID: 23974709, PMCID: PMC3785563.

  

Brahmachari, S., P.Ge, S.H. Lee, D. Kim, S.S. Karuppagounder, M. Kumar, X. Mao, Y. Lee, O. Pletnikova, J.C. Troncoso, V.L. Dawson, T.M.Dawson and H.S. Ko. “Activation of tyrosine kinase c-Abl contributes to a-Synuclein-Induced Neurodegeneration.” J. Clinical Investigation, 26:2970-2988.  doi: 10.1172/JCI85456. (2016). PMID: 27348587, PMCID: PMC4966315.

 

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Kam, T.-I., X. Mao, H. Park, S.S. Karuppagounder, S.-C. Chou, G.E. Umanah, S. Brahmachari, S.P. Yun, N. Panicker, R. Chen, S.A. Andrabi, C. Qi, G.G. Poirier, O. Pletnikova, J.C. Troncoso, L.M. Bekris, J.B. Leverenz, A.Pantelyat, H.S. Ko, L.S. Rosenthal, T.M. Dawson and V.L. Dawson “Poly (ADP-ribose) Drives Pathologic a-Synuclein Neurodegeneration.” *Both authors contributed equally, Science 362, eaat8407 (2018). DOI: 10.1126/science.aat8407, PMID: 30385548, PMCID: PMC6431793.

 

Brahmachari, S., C. Yuan, S.S. Karuppagounder, P.Ge, D. Kim, A. Liu, H. Jiang, X. Mao, Y. Lee, D.A. Swing, L. Tessarollo, H.S. Ko, V.L. Dawson and T.M. Dawson. “Parkin interacting substrate zinc finger protein 746 is a pathologic mediator in Parkinson’s disease, Brain, 142:2380-2401 (2019) DOI: 10.1093/brain/awz172 PMID: 31237944, PMCID: PMC6658849.

Pirooznia, S.K., C. Yuan, M. Khan, S.S. Karuppagounder, L. Wang, Y. Xiong, S.U. Kang, Y. Lee, V.L. Dawson and T.M. Dawson. “PARIS induced defects in mitochondrial biogenesis drives dopamine neuron loss under conditions of Parkin or PINK1 deficiency.” Molecular Neurodegneration, Mar 5;15(1):17. doi: 10.1186/s13024-020-00363-x. PMID: 32138754