Systems metabolism


We are a young research group at Karolinska Institutet in Stockholm, Sweden, specializing in detailed analyses of cellular metabolism using modern measurement techniques and mathematical models. Our work aims for a deeper and more quantitative understanding of how various cell types in the human body process nutrients to harvest energy and synthesize macromolecules. In particular, we are interested in the metabolic derangements that occur in cancer cells, but also in specialized modes metabolism unique to other cell types.

Our work involves large-scale data integration, mathematical models of metabolism, transcriptomics, mass-spectrometry based metabolite profiling, and cellular physiology. We are working in close collaboration with colleagues at the University of California, San Diego, as well as Harvard University and the Broad Institute (Boston).


Selected publications

Lyutvinskiy Y, Watrous JD, Jain M, Nilsson R. A Web Service Framework for Interactive Analysis of Metabolomics Data. Anal Chem. 2017 Jun 6;89(11):5713-5718.

Nilsson R, Roci I, Watrous J, Jain M. Estimation of flux ratios without uptake or release data: application to serine and methionine metabolism. Metab Eng. 2017 Sep;43(Pt B):137-146.

Roci I, Gallart-Ayala H, Watrous J, Jain M, Wheelock CE, Nilsson R. A Method for Measuring Metabolism in Sorted Subpopulations of Complex Cell Communities Using Stable Isotope Tracing. J Vis Exp. 2017 Feb 4;(120).

Nilsson R, Jain M. Simultaneous tracing of carbon and nitrogen isotopes in human cells. Molecular Biosystems 2016 May 24;12(6):1929-37.

Roci I, Gallart-Ayala H, Schmidt A, Watrous J, Jain M, Wheelock CE, Nilsson R. Metabolite Profiling and Stable Isotope Tracing in Sorted Subpopulations of Mammalian Cells. Anal Chem. 2016 Mar 1;88(5):2707-13.

Gustafsson Sheppard N, et al. The folate-coupled enzyme MTHFD2 is a nuclear protein and promotes cell proliferation. Scientific Reports 5:15029, 2015.

Jain M, Ngoy S, Sheth SA, Swanson RA, Rhee EP, Liao R, Clish CB, Mootha VK, Nilsson R. A systematic survey of lipids across mouse tissues. Am J Physiol Endocrinol Metab. 2014 Apr 15;306(8):E854-68.

Nilsson R, Jain M, Madhusudhan N, Sheppard NG, Strittmatter L, Kampf C, Huang J, Asplund A, Mootha VK. Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer. Nat Commun. 2014;5:3128.

Sharma S, Quintana A, Findlay GM, Mettlen M, Baust B, Jain M, Nilsson R, Rao A, Hogan PG. An siRNA screen for NFAT activation identifies septins as coordinators of store-operated Ca2+ entry. Nature. 2013 Jul 11;499(7457):238-42.

Maleki S, Björck HM, Folkersen L, Nilsson R, Renner J, Caidahl K, Franco-Cereceda A, Länne T, Eriksson P. Identification of a novel flow-mediated gene expression signature in patients with bicuspid aortic valve. J Mol Med (Berl). 2013 Jan;91(1):129-39.

Jain M, Nilsson R, Sharma S, Madhusudhan N, Kitami T, Souza AL, Kafri R, Kirschner MW, Clish CB, Mootha VK. Metabolite Profiling Identifies a Key Role for Glycine in Rapid Cancer Cell Proliferation. Science. 2012 May 25;336(6084):1040-4.

Gohil VM, Nilsson R, Belcher-Timme CA, Luo B, Root DE, Mootha VK. Mitochondrial and nuclear genomic responses to loss of LRPPRC expression. J Biol Chem. 2010 Apr 30;285(18):13742-7. 

Gohil VM, Sheth SA, Nilsson R, Wojtovich AP, Lee JH, Perocchi F, Chen W, Clish CB, Ayata C, Brookes PS, Mootha VK. Nutrient-sensitized screening for drugs that shift energy metabolism from mitochondrial respiration to glycolysis. Nat Biotechnol. 2010 Mar;28(3):249-55.

Baughman JM, Nilsson R, Gohil VM, Arlow DH, Gauhar Z, Mootha VK. A Computational Screen for Regulators of Oxidative Phosphorylation Implicates SLIRP in Mitochondrial RNA Homeostasis. PLoS Genet. 2009 Aug;5(8):e1000590.

Nilsson R, Schultz IJ, Pierce EL, Soltis KA, Naranuntarat A, Ward DM, Baughman JM, Paradkar PN, Kingsley PD, Culotta VC, Kaplan J, Palis J, Paw BH, Mootha VK. Discovery of Genes Essential for Heme Biosynthesis through Large-Scale Gene Expression Analysis. Cell Metab. 2009 Aug;10(2):119-30.

Peña JM, Nilsson R, Björkegren J, Tegnér J. An Algorithm for Reading Dependencies from the Minimal Undirected Independence Map of a Graphoid that Satisfies Weak Transitivity. The Journal of Machine Learning Research. 2009 10, 1071–1094.

Nilsson R, Björkegren J, Tegnér J. On reliable discovery of molecular signatures. BMC Bioinformatics. 2009 Jan 29;10:38.

Skogsberg J, Dicker A, Rydén M, Aström G, Nilsson R, Bhuiyan H, Vitols S, Mairal A, Langin D, Alberts P, Walum E, Tegnér J, Hamsten A, Arner P, Björkegren J. ApoB100-LDL Acts as a Metabolic Signal from Liver to Peripheral Fat Causing Inhibition of Lipolysis in Adipocytes. PLoS One. 2008;3(11):e3771.

Skogsberg J, Lundström J, Kovacs A, Nilsson R, Noori P, Maleki S, Köhler M, Hamsten A, Tegnér J, Björkegren J Transcriptional Profiling Uncovers a Network of Cholesterol-Responsive Atherosclerosis Target Genes. PLoS Genet. 2008 Mar 14;4(3):e1000036.

Kovacs A, Tornvall P, Nilsson R, Tegnér J, Hamsten A, Björkegren J. Human C-reactive protein slows atherosclerosis development in a mouse model with human-like hypercholesterolemia. PNAS 2007 Aug 21;104(34):13768-73.

Nilsson R, Peña JM, Björkegren J, Tegnér J. Consistent feature selection for pattern recognition in polynomial time. Journal of Machine Learning Research 8, pp. 589–612, 2007.

Nilsson R, Peña JM, Björkegren J, Tegnér J. Detecting multivariate differential expression patterns. BMC Bioinformatics. 2007 May 9;8:150.

Peña JM, Nilsson R, Björkegren J, Tegnér J. Towards scalable and data efficient learning of Markov boundaries. International Journal of Approximate Reasoning 2007 45:2, 211–232.

Tegnér J, Nilsson R, Bajic VB, Björkegren J, Ravasi T. Systems biology of innate immunity. Cell Immunol. 2006 Dec; 244(2): 105–109.

Nilsson R, Bajic VB, Suzuki H, di Bernardo D, Björkegren J, Katayama S, Reid JF, Sweet MJ, Gariboldi M, Carninci P, Hayashizaki Y, Hume DA, Tegner J, Ravasi T. Transcriptional network dynamics in macrophage activation. Genomics. 2006 Aug;88(2):133-42.

Nilsson R, Peña JM, Björkegren J, Tegnér J. Evaluating feature selection for SVMs in high dimensions. In proc. of the 17th European Conference on Machine Learning. 2006 pp. 719–726.

Peña JM, Nilsson R, Björkegren J, Tegnér J. Identifying relevant nodes without learning the model. In proc. of the 22nd Conference on Uncertainty in Artificial Intelligence. 2006 pp. 367–374.

Peña JM, Nilsson R, Björkegren J, Tegnér J. Reading dependencies from the minimal undirected independence map of a graphoid that satisfies weak transitivity. In proc. of the 3rd European Workshop on Probabilistic Graphical Models. 2006 pp. 247–254.

Nilsson R, Björkegren J, Tegnér J. A flexible implementation for support vector machines. The Mathematica Journal. 2006 10:1, pp. 114–127.

Nilsson R, Björkegren J, Tegnér J. A powerful differential expression test for probe-level oligonucleotide microarray data. In proc. of the 2nd IEEE International Workshop on Genomic Signal Processing and Statistics. 2004 pp. 10–14.