Gunnar Hargus, MD, PhD
Overview
Email: gh2374@cumc.columbia.edu
Academic Appointments
- Assistant Professor of Pathology & Cell Biology
Hospital Affiliations
- NewYork-Presbyterian / Columbia University Irving Medical Center
Languages
- German
Gender
- Male
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Credentials & Experience
Education & Training
- MD, Med Hochschule Lubeck (Germany)
- PhD, Univ of Hamburg/Center for Molecular Neurobiology Hannover (Germany)
- Residency: NewYork-Presbyterian Hospital/Columbia University Medical Center
- Residency: University of Munster/Max Planck Biomedicine Institute (Germany)
- Fellowship: NewYork-Presbyterian Hospital/Columbia University Medical Center
Board Certifications
- Neuropathology
Research
Our research focuses on pluripotent stem cells and their application in developmental biology and in modeling of neurodegenerative diseases with a special focus on frontotemporal dementia (FTD). We have derived induced pluripotent stem (iPS) cells from patients with FTD carrying mutations in the gene encoding the microtubule-associated protein tau as an in vitro model for FTD. These mutations lead to abundant deposition of hyperphosphorylated tau protein within neurons and glial cells in various brain regions including the frontotemporal lobes and the brain stem.
Our aim is to identify mechanisms that lead to neural degeneration in FTD. We apply optimized differentiation protocols to efficiently derive neurons and astrocytes from patient-iPS cells and from CRISPR/CAS9-gene corrected control cells. We currently study metabolic profiles in FTD neurons and astrocytes and we determine phenotypes in these cells at a single cell level by applying single cell RNA sequencing.
Selected Publications
1. Soldner F, Hockemeyer D, Beard C, Gao Q, Bell GW, Cook EG, Hargus G, Blak A, Cooper O, Mitalipova M, Isacson O, Jaenisch R (2009): Parkinson's disease patient- derived induced pluripotent stem cells free of viral reprogramming factors. Cell 136 (5): 964-77
2. Hargus G, Cooper O, Deleidi M, Levy A, Lee K, Marlow E, Yow A, Soldner F, Hockemeyer D, Hallett P, Osborn P, Jaenisch R, and Isacson O (2010): Differentiated Parkinson patient-derived iPS cells grow in the adult rodent brain and reduce motor asymmetry in Parkinsonian rats. Proc Natl Acad Sci USA 107 (36): 15921-6
3. Cooper O, Seo H, Andrabi S, Sundberg M, McLean J, Carrillo-Reid L, Xie Z, Osborn T, Hargus G, Deleidi M, Lawson T, Bogetofte-Thomasen H, Perez-Torres E, Clark L, Moskowitz C, Guardia-Laguarta C, Mazzulli J, Chen L, Volpicelli-Daley L, Romero N, Jiang H, Uitti RJ, Huang L, Opala G, Feng J, Ross OA, Trojanowski JQ, Lee V, Krainc D, Marder K, Pzedborski S, Surmeier J, Wszolek ZK, Dawson TM, Isacson O (2012): Pharmacological Rescue of Mitochondrial Deficits in iPSC-Derived Neural Cells from Patients with Familial Parkinson's Disease. Science Translational Medicine 4(141): 141ra90
4. Reinhardt P, Schmid B, Burbulla LF, Schöndorf DC, Wagner L, Glatza M, Höing S, Hargus G, Heck SA, Dhingra A, Wu G, Müller S, Brockmann K, Kluba T, Maisel M, Krüger R, Berg D, Tsytsyura Y, Thiel CS, Psathaki OE, Klingauf J, Kuhlmann T, Klewin M, Müller H, Gasser T, Schöler HR, Sterneckert J (2013): Genetic correction of a LRRK2 mutation in human iPSCs links Parkinsonian neurodegeneration to ERK- dependent changes in gene expression. Cell Stem Cell 7; 12 (3):354-67
5. Hargus G*, Ehrlich M*, Araúzo-Bravo MJ, Hemmer K, Hallmann AL, Reinhardt P, Kim KP, Adachi K, Santourlidis S, Ghanjati F, Fauser M, Ossig C, Storch A, Kim JB, Schwamborn JC, Sterneckert J, Schöler HR, Kuhlmann T, Zaehres H. (2014): Origin- dependent neural cell identities in differentiated human iPSCs in vitro and after transplantation into the mouse brain. Cell Rep. 8(6):1697-703
6. Hargus G, Ehrlich M, Hallmann AL, Kuhlmann T. (2014): Human stem cell models of neurodegeneration - A novel approach to study disease development. Acta Neuropathologica, 127(2):151-73
7. Ehrlich M, Hallmann AL, Reinhardt P, Araúzo-Bravo MJ, Korr S, Röpke A, Psathaki OE, Ehling P, Meuth SG, Oblak AL, Murrell JR, Ghetti B, Zaehres H, Schöler HR, Sterneckert J, Kuhlmann T*, Hargus G* (2015): Distinct neurodegenerative changes in an induced pluripotent stem cell model of frontotemporal dementia linked to mutant TAU protein. Stem Cell Reports Jul 14;5(1):83-96
8. Hallmann AL, Araúzo-Bravo MJ, Zerfass C, Senner V, Ehrlich M, Psathaki OE, Han DW, Tapia N, Zaehres H, Schöler HR, Kuhlmann T*, Hargus G*. (2016): Comparative transcriptome analysis in induced neural stem cells reveals defined neural cell identities in vitro and after transplantation into the adult rodent brain. Stem Cell Research 2016; May;16(3):776-81
9. Hallmann AL, Araúzo-Bravo MJ, Mavrommatis L, Ehrlich M, RÓ§pke A, Brockhaus J, Missler M, Sterneckert J, Schöler HR, Kuhlmann T*, Zaehres H*, Hargus G* (2017): Astrocyte pathology in a human neural stem cell model of frontotemporal dementia caused by mutant TAU protein. Scientific Reports 7:42991
For a complete list of publications, please visit PubMed.gov