Clinical Phenomics

CARAMBA performs pre-clinical and clinical research, targeting endogenous and exogenous molecules, in combination with state-of-the-art bioinformatics with the global goal to improve human health care and disease prevention.

Group member Position
Kim Kultima Associate Professor
Torbjörn Åkerfeldt Physician
Eva Freyhult Researcher/Bioinformatician
Payam Khoonsari Emami Researcher/Bioinformatician
Stephanie Herman PhD student
Christina Zhukovsky PhD student
Niclas Rollborn Laboratory engineer/PhD student

PROJECTS

Clinical Proteomics & Metabolomics
We have developed and implemented mass spectrometry-based methods for proteomics and metabolomics, including targeted and untargeted analyses of hormones, lipids and small signaling molecules in human cerebrospinal fluid and blood samples. These signals are further connected to biological pathways and demographic patient data. We are currently involved in three large efforts;

Characterization and stratification of multiple sclerosis phenotypes
Improve diagnostic markers for chronic pain states
Early detection of Alzheimer’s disease

We are also part of the EU Horizon 2020 project PhenoMeNal with focus on implementing clinical metabolomics into the clinic.

PUBLICATIONS

Carlsson, H., K. Hjorton, S. Abujrais, L. Rönnblom, T. Åkerfeldt, K. Kultima, Measurement of hydroxychloroquine in blood from SLE patients using LC-HRMS – Evaluation of whole blood, plasma and serum as sample matrices. 2020. Arthritis Research & Therapy. Accepted.

Wiberg, A., U. Olsson-Stromberg, S. Herman, K. Kultima, and J. Burman, Profound but Transient Changes in the Inflammatory Milieu of the Blood During Autologous Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant, 2020. 26(1): p. 50-57.

Carlsson, H., S. Abujrais, S. Herman, P.E. Khoonsari, T. Akerfeldt, A. Svenningsson, J. Burman, and K. Kultima, Targeted metabolomics of CSF in healthy individuals and patients with secondary progressive multiple sclerosis using high-resolution mass spectrometry. Metabolomics, 2020. 16(2): p. 26.

Remnestal, J., L. Öijerstedt, A. Ullgren, J. Olofosson, S. Bergström, K. Kultima, M. Ingelsson, L. Kilander, M. Uhlen, A. Månberg, C. Graff, and P. Nilsson, Altered levels of CSF proteins in patients with FTD, presymptomatic mutation carriers and non-carriers. Transl Neurodegener, 2020. Accepted.

Emmerich, A., J. Wellstein, E. Ossipova, I. Baumann, J. Lengquist, K. Kultima, D. Steinhilber, and M. Saul, Proteomics-based characterization of miR-574-5p decoy to CUGBP1 suggests specificity for mPGES-1 regulation in human lung cancer cells. Front Pharmacol, 2020. 11(March 2020).

Hamdeh, S., P.E. Khoonsari, G. Shevchenko, T. Gordh, H. Ericson, and K. Kultima, Increased CSF levels of apolipoproteins and complement factors in trigeminal neuralgia patients – in depth proteomic analysis using mass spectrometry. J Pain, 2020. Accepted.

2019

Abujrais, S., M. Olovsson, M. Ahnoff, A.J. Rasmusson, A. Larsson, T. Akerfeldt, and K. Kultima, A sensitive method detecting trace levels of levonorgestrel using LC-HRMS. Contraception, 2019. 100(3): p. 247-249.

Emami Khoonsari, P., P. Moreno, S. Bergmann, J. Burman, M. Capuccini, M. Carone, M. Cascante, P. de Atauri, C. Foguet, A.N. Gonzalez-Beltran, T. Hankemeier, K. Haug, S. He, S. Herman, D. Johnson, N. Kale, A. Larsson, S. Neumann, K. Peters, L. Pireddu, P. Rocca-Serra, P. Roger, R. Rueedi, C. Ruttkies, N. Sadawi, R.M. Salek, S.A. Sansone, D. Schober, V. Selivanov, E.A. Thevenot, M. van Vliet, G. Zanetti, C. Steinbeck, K. Kultima, and O. Spjuth, Interoperable and scalable data analysis with microservices: applications in metabolomics. Bioinformatics, 2019. 35(19): p. 3752-3760.

Ericson, H., S. Abu Hamdeh, E. Freyhult, F. Stiger, E. Backryd, A. Svenningsson, T. Gordh, and K. Kultima, Cerebrospinal fluid biomarkers of inflammation in trigeminal neuralgia patients operated with microvascular decompression. Pain, 2019. 160(11): p. 2603-2611.

Herman, S., V. Niemela, P. Emami Khoonsari, J. Sundblom, J. Burman, A.M. Landtblom, O. Spjuth, D. Nyholm, and K. Kultima, Alterations in the tyrosine and phenylalanine pathways revealed by biochemical profiling in cerebrospinal fluid of Huntington’s disease subjects. Sci Rep, 2019. 9(1): p. 4129.

Novella, J.A., P. Emami Khoonsari, S. Herman, D. Whitenack, M. Capuccini, J. Burman, K. Kultima, and O. Spjuth, Container-based bioinformatics with Pachyderm. Bioinformatics, 2019. 35(5): p. 839-846.

Saul, M.J., A.B. Hegewald, A.C. Emmerich, E. Ossipova, M. Vogel, I. Baumann, K. Kultima, J. Lengqivst, D. Steinhilber, and P.J. Jakobsson, Mass Spectrometry-Based Proteomics Approach Characterizes the Dual Functionality of miR-328 in Monocytes. Front Pharmacol, 2019. 10: p. 640.

Feresiadou, A., K. Nilsson, M. Ingelsson, R. Press, I. Kmezic, I. Nygren, A. Svenningsson, V. Niemela, T. Gordh, J. Cunningham, K. Kultima, A. Larsson, and J. Burman, Measurement of sCD27 in the cerebrospinal fluid identifies patients with neuroinflammatory disease. J Neuroimmunol, 2019. 332: p. 31-36.

Herman, S., T. Akerfeldt, O. Spjuth, J. Burman, and K. Kultima, Biochemical Differences in Cerebrospinal Fluid between Secondary Progressive and Relapsing(-)Remitting Multiple Sclerosis. Cells, 2019. 8(2).

Khoonsari, P.E., S. Musunri, S. Herman, C.I. Svensson, L. Tanum, T. Gordh, and K. Kultima, Systematic analysis of the cerebrospinal fluid proteome of fibromyalgia patients. J Proteomics, 2019. 190: p. 35-43.

Khoonsari, P.E., E. Ossipova, J. Lengqvist, C.I. Svensson, E. Kosek, D. Kadetoff, P.J. Jakobsson, K. Kultima*, and J. Lampa*, The human CSF pain proteome. J Proteomics, 2019. 190: p. 67-76. *Kultima & Lampa contributed equally as senior authors.

Peters, K., J. Bradbury, S. Bergmann, M. Capuccini, M. Cascante, P. de Atauri, T.M.D. Ebbels, C. Foguet, R. Glen, A. Gonzalez-Beltran, U.L. Gunther, E. Handakas, T. Hankemeier, K. Haug, S. Herman, P. Holub, M. Izzo, D. Jacob, D. Johnson, F. Jourdan, N. Kale, I. Karaman, B. Khalili, P. Emami Khonsari, K. Kultima, S. Lampa, A. Larsson, C. Ludwig, P. Moreno, S. Neumann, J.A. Novella, C. O’Donovan, J.T.M. Pearce, A. Peluso, M.E. Piras, L. Pireddu, M.A.C. Reed, P. Rocca-Serra, P. Roger, A. Rosato, R. Rueedi, C. Ruttkies, N. Sadawi, R.M. Salek, S.A. Sansone, V. Selivanov, O. Spjuth, D. Schober, E.A. Thevenot, M. Tomasoni, M. van Rijswijk, M. van Vliet, M.R. Viant, R.J.M. Weber, G. Zanetti, and C. Steinbeck, PhenoMeNal: processing and analysis of metabolomics data in the cloud. Gigascience, 2019. 8(2).

Larsson, A., J. Tyden, J. Johansson, M. Lipcsey, M. Bergquist, K. Kultima, and A. Mandic-Havelka, Calprotectin is superior to procalcitonin as a sepsis marker and predictor of 30-day mortality in intensive care patients. Scand J Clin Lab Invest, 2019: p. 1-6.

Bersellini Farinotti, A., G. Wigerblad, D. Nascimento, D.B. Bas, C. Morado Urbina, K.S. Nandakumar, K. Sandor, B. Xu, S. Abdelmoaty, M.A. Hunt, K. Angeby Moller, A. Baharpoor, J. Sinclair, K. Jardemark, J.T. Lanner, I. Khmaladze, L.E. Borm, L. Zhang, F. Wermeling, M.S. Cragg, J. Lengqvist, A.J. Chabot-Dore, L. Diatchenko, I. Belfer, M. Collin, K. Kultima, B. Heyman, J.M. Jimenez-Andrade, S. Codeluppi, R. Holmdahl, and C.I. Svensson, Cartilage-binding antibodies induce pain through immune complex-mediated activation of neurons. J Exp Med, 2019. 216(8): p. 1904-1924.

Idborg, H., A. Zandian, E. Ossipova, E. Wigren, C. Preger, F. Mobarrez, A. Checa, A. Sohrabian, P. Pucholt, J.K. Sandling, C. Fernandes-Cerqueira, J. Ronnelid, V. Oke, G. Grosso, M. Kvarnstrom, A. Larsson, C.E. Wheelock, A.C. Syvanen, L. Ronnblom, K. Kultima, H. Persson, S. Graslund, I. Gunnarsson, P. Nilsson, E. Svenungsson, and P.J. Jakobsson, Circulating Levels of Interferon Regulatory Factor-5 Associates With Subgroups of Systemic Lupus Erythematosus Patients. Front Immunol, 2019. 10: p. 1029.

Bergqvist, F., E. Ossipova, H. Idborg, J. Raouf, A. Checa, K. Englund, P. Englund, P.E. Khoonsari, K. Kultima, C.E. Wheelock, K. Larsson, M. Korotkova, and P.J. Jakobsson, Inhibition of mPGES-1 or COX-2 Results in Different Proteomic and Lipidomic Profiles in A549 Lung Cancer Cells. Front Pharmacol, 2019. 10: p. 636.

Karakitsou, E., C. Foguet, P. Atauri, K. Kultima, P. Khoonsari, V. Santos, E. Saccenti, A. Rosato, and M. Cascante, Metabolomics in Systems Medicine- an overview of methods and applications. Current Opinion in Systems Biology, 2019. 15(June 2019): p. 91-99.

Khoonsari, P.E., G. Shevchenko, S. Herman, J. Remnestal, V. Giedraitis, R. Brundin, M. Degerman Gunnarsson, L. Kilander, H. Zetterberg, P. Nilsson, L. Lannfelt, M. Ingelsson, and K. Kultima, Improved Differential Diagnosis of Alzheimer’s Disease by Integrating ELISA and Mass Spectrometry-Based Cerebrospinal Fluid Biomarkers. J Alzheimers Dis, 2019. 67(2): p. 639-651.

2018

Herman, S., P.E. Khoonsari, A. Tolf, J. Steinmetz, H. Zetterberg, T. Akerfeldt, P.J. Jakobsson, A. Larsson, O. Spjuth, J. Burman, and K. Kultima, Integration of magnetic resonance imaging and protein and metabolite CSF measurements to enable early diagnosis of secondary progressive multiple sclerosis.Theranostics, 2018. 8(16): p. 4477-4490. (IF: 8.5). 10.7150/thno.26249.

Sandor, K., S. Krishnan, N.M. Agalave, E. Krock, J.V. Salcido, T. Fernandez-Zafra, P.E. Khoonsari, C.I. Svensson, and K. Kultima, Spinal injection of newly identified cerebellin-1 and cerebellin-2 peptides induce mechanical hypersensitivity in mice.Neuropeptides, 2018. 69: p. 53-59. (IF: 2.9). 10.1016/j.npep.2018.04.004.

2017

Herman, S., P. Emami Khoonsari, O. Aftab, S. Krishnan, E. Strombom, R. Larsson, U. Hammerling, O. Spjuth, K. Kultima, and M. Gustafsson, Mass spectrometry based metabolomics for in vitro systems pharmacology: pitfalls, challenges, and computational solutions.Metabolomics, 2017. 13(7): p. 79. (IF: 3.5). 10.1007/s11306-017-1213-z. Kultima & Gustafsson contributed equally as senior authors.

Almandoz-Gil, L., H. Welander, E. Ihse, P.E. Khoonsari, S. Musunuri, C. Lendel, J. Sigvardson, M. Karlsson, M. Ingelsson, K. Kultima, and J. Bergstrom, Low molar excess of 4-oxo-2-nonenal and 4-hydroxy-2-nonenal promote oligomerization of alpha-synuclein through different pathways.Free Radic Biol Med, 2017. 110: p. 421-431. (IF: 6.0). 10.1016/j.freeradbiomed.2017.07.004. Kultima & Bergström contributed equally as senior authors.

van Rijswijk, M., C. Beirnaert, C. Caron, M. Cascante, V. Dominguez, W.B. Dunn, T.M.D. Ebbels, F. Giacomoni, A. Gonzalez-Beltran, T. Hankemeier, K. Haug, J.L. Izquierdo-Garcia, R.C. Jimenez, F. Jourdan, N. Kale, M.I. Klapa, O. Kohlbacher, K. Koort, K. Kultima, G. Le Corguille, P. Moreno, N.K. Moschonas, S. Neumann, C. O’Donovan, M. Reczko, P. Rocca-Serra, A. Rosato, R.M. Salek, S.A. Sansone, V. Satagopam, D. Schober, R. Shimmo, R.A. Spicer, O. Spjuth, E.A. Thevenot, M.R. Viant, R.J.M. Weber, E.L. Willighagen, G. Zanetti, and C. Steinbeck, The future of metabolomics in ELIXIR.F1000Res, 2017. 6. (IF: NA). 10.12688/f1000research.12342.2.

 Nikitidou, E., P.E. Khoonsari, G. Shevchenko, M. Ingelsson, K. Kultima, and A. Erlandsson,Increased Release of Apolipoprotein E in Extracellular Vesicles Following Amyloid-beta Protofibril Exposure of Neuroglial Co-Cultures.J Alzheimers Dis, 2017. 60(1): p. 305-321. (IF: 3.5). 10.3233/jad-170278.

2016

Khoonsari, P.E., A. Haggmark, M. Lonnberg, M. Mikus, L. Kilander, L. Lannfelt, J. Bergquist, M. Ingelsson, P. Nilsson, K. Kultima, and G. Shevchenko, Analysis of the Cerebrospinal Fluid Proteome in Alzheimer’s Disease.PLoS One, 2016. 11(3): p. e0150672. (IF: 2.8). 10.1371/journal.pone.0150672. Kultima & Shevchenko contributed equally as senior authors.

Remnestal, J., D. Just, N. Mitsios, C. Fredolini, J. Mulder, J.M. Schwenk, M. Uhlen, K. Kultima, M. Ingelsson, L. Kilander, L. Lannfelt, P. Svenningsson, B. Nellgard, H. Zetterberg, K. Blennow, P. Nilsson, and A. Haggmark-Manberg, CSF profiling of the human brain enriched proteome reveals associations of neuromodulin and neurogranin to Alzheimer’s disease.Proteomics Clin Appl, 2016. 10(12): p. 1242-1253. (IF: 3.6). 10.1002/prca.201500150.

 Lind, A.L., P. Emami Khoonsari, M. Sjodin, L. Katila, M. Wetterhall, T. Gordh, and K. Kultima, Spinal Cord Stimulation Alters Protein Levels in the Cerebrospinal Fluid of Neuropathic Pain Patients: A Proteomic Mass Spectrometric Analysis.Neuromodulation, 2016. 19(6): p. 549-62. (IF: 2.8). 10.1111/ner.12473.

Musunuri, S., P.E. Khoonsari, M. Mikus, M. Wetterhall, A. Haggmark-Manberg, L. Lannfelt, A. Erlandsson, J. Bergquist, M. Ingelsson, G. Shevchenko, P. Nilsson, and K. Kultima, Increased Levels of Extracellular Microvesicle Markers and Decreased Levels of Endocytic/Exocytic Proteins in the Alzheimer’s Disease Brain.J Alzheimers Dis, 2016. 54(4): p. 1671-1686. (IF: 3.5). 10.3233/jad-160271.

 Senkowski, W., M. Jarvius, J. Rubin, J. Lengqvist, M.G. Gustafsson, P. Nygren, K. Kultima, R. Larsson, and M. Fryknas, Large-Scale Gene Expression Profiling Platform for Identification of Context-Dependent Drug Responses in Multicellular Tumor Spheroids.Cell Chem Biol, 2016. 23(11): p. 1428-1438. (IF: 4.5). 10.1016/j.chembiol.2016.09.013.

Adori, C., S. Barde, S. Vas, K. Ebner, J. Su, C. Svensson, A.A. Mathe, N. Singewald, R.R. Reinscheid, M. Uhlen, K. Kultima, G. Bagdy, and T. Hokfelt, Exploring the role of neuropeptide S in the regulation of arousal: a functional anatomical study.Brain Struct Funct, 2016. 221(7): p. 3521-46. (IF: 4.2). 10.1007/s00429-015-1117-5.

2015

Musunuri, S., K. Kultima, B.C. Richard, M. Ingelsson, L. Lannfelt, J. Bergquist, and G. Shevchenko, Micellar extraction possesses a new advantage for the analysis of Alzheimer’s disease brain proteome.Anal Bioanal Chem, 2015. 407(4): p. 1041-57. (IF: 3.3). 10.1007/s00216-014-8320-8.

Musunuri, S., M. Wetterhall, M. Ingelsson, L. Lannfelt, K. Artemenko, J. Bergquist, K. Kultima, and G. Shevchenko, Quantification of the brain proteome in Alzheimer’s disease using multiplexed mass spectrometry.J Proteome Res, 2014. 13(4): p. 2056-68. (IF: 4.0). 10.1021/pr401202d.

Su, J., K. Sandor, K. Skold, T. Hokfelt, C.I. Svensson, and K. Kultima, Identification and quantification of neuropeptides in naive mouse spinal cord using mass spectrometry reveals [des-Ser1]-cerebellin as a novel modulator of nociception.J Neurochem, 2014. 130(2): p. 199-214. (IF: 4.6). 10.1111/jnc.12730.

COLLABORATORS