Experimental Psychiatry and Neurology
Our research is aimed at understanding molecular mechanisms causing disease by disruption in higher-level brain functioning.
In particular, we are interested in the interplay between neurons and glia cells for the development and maintenance of appropriate brain circuits.
By using cellular reprogramming we create subject-specific cellular models including neurons and glia-like cells derived from diseased subjects and matched healthy controls. These models are then amenable for genetic engineering as well as compound screening.
Our research is carried out in close collaboration with the clinic and includes large-scale systematic collection of clinical data and biological material from a variety of subjects with chronic brain disorders such as schizophrenia and bipolar disorders.
Collecting interdisciplinary data for each subject we are also able to follow up our findings from subject-specific cell cultures with for example analyses of cerebrospinal fluid or data obtained from positron-emission tomography scans.
- Jessica Gracias
- Funda Orhan
- Carl Sellgren, Group leader
- Sanna Bruno
- Samudyata Samudyata
- Ana Oliveira
- Sravan Goparaju
The current projects in our laboratory can be divided into four major categories:
- Assay development including cellular high-throughput approaches as well as more complete models such as organoids.
- Patient vs. control comparisons.
- Disease-orientated mechanistic studies using for example genetic engineering.
- High-throughput compound screening.
- Marianne och Marcus Wallenbergs Stiftelse
- Knut och Alice Wallenbergs Stiftelse
- Swedish Research Council
Our research team works in close co-operation with several national and international groups in order to build a representative biobank of live cells from subjects with psychiatric and neurological disorders.
We are part of the Karolinska Schizophrenia Project (KaSP) and among our close collaborators are also Massachusetts General Hospital Neurobank (PI: Roy Perlis/Harvard Medical School) and Clinically Integrated Brain Research Initiative Sweden (PI: Mikael Landén/ Sahlgrenska Akademin vid Göteborgs universitet).
Increased synapse elimination by microglia in schizophrenia patient-derived models of synaptic pruning.
Sellgren CM, Gracias J, Watmuff B, Biag JD, Thanos JM, Whittredge PB, et al
Nat. Neurosci. 2019 03;22(3):374-385
Patient-specific models of microglia-mediated engulfment of synapses and neural progenitors.
Sellgren CM, Sheridan SD, Gracias J, Xuan D, Fu T, Perlis RH
Mol. Psychiatry 2017 02;22(2):170-177
A genome-wide association study of kynurenic acid in cerebrospinal fluid: implications for psychosis and cognitive impairment in bipolar disorder.
Sellgren CM, Kegel ME, Bergen SE, Ekman CJ, Olsson S, Larsson M, et al
Mol. Psychiatry 2016 10;21(10):1342-50
CSF GABA is reduced in first-episode psychosis and associates to symptom severity.
Orhan F, Fatouros-Bergman H, Goiny M, Malmqvist A, Piehl F, , et al
Mol. Psychiatry 2018 05;23(5):1244-1250
Blood metabolomics analysis identifies abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism in bipolar disorder.
Yoshimi N, Futamura T, Kakumoto K, Salehi AM, Sellgren CM, Holmén-Larsson J, et al
BBA Clin 2016 Jun;5():151-8
Markers of neuroinflammation and neuronal injury in bipolar disorder: Relation to prospective clinical outcomes.
Isgren A, Sellgren C, Ekman CJ, Holmén-Larsson J, Blennow K, Zetterberg H, et al
Brain Behav. Immun. 2017 Oct;65():195-201