Team

Research Focus

Our research group aims to understand the immuno-regulatory transcriptional pathways in the pathology of skeletal and cardiac muscle disorders.

Pro-inflammatory pathways play a major role in the pathophysiology of skeletal and cardiovascular disorders. Immune cells mediate the signaling pathways regulating activation of innate immune signaling through multiple transcriptional regulatory check points changing cells from healthy to diseased state. We have shown that interferon signaling plays an important role in controlling immune-metabolism in the state of obesity and diabetes in mice and humans. Our current research is focused towards understanding of the intracellular transcriptional, molecular and metabolic networks of altered inflammatory response upon cellular damage. The overall goal is to identify new mechanisms and molecules that can be therapeutically targeted using novel tools to understand disease progression in muscle dystrophy and cardiomyopathy.

Research Techniques

We use transgenic animal models and a wide range of molecular biology techniques, enzyme activity assays, lipidomics, metagenomics, metabolomics and proteomics, Reporter-based assays, Seahorse-assays, and FACS analysis to address our scientific questions.

Collaborations

Prof. Norbert Frey, Heidelberg University Hospital

PD. Dr.rer.nat. Ashraf Rangrez, Heidelberg University Hospital

Prof. Florian Leuschner, Heidelberg University Hospital

Prof. Lorenz Lehmann, Heidelberg University Hospital

Prof. Johannes Backs, Heidelberg University Hospital

Prof. Marc Freichel, Heidelberg University Hospital

Prof. Almut Schulze, Heidelberg University Hospital

Prof. Joerg Heeren, University Medical Center-Hamburg Eppendorf

Prof. Thomas Eschenhagen, University Medical Center-Hamburg Eppendorf

Funding

DFG

DZHK

Vacancies

We are currently seeking motivated MD students.

Highly motivated and talented students interested in PhD study in our group are encouraged to apply.

Contact

Dr. rer. nat. Manju Kumari
University Hospital Heidelberg
Innere Medizin III
Im Neuenheimer Feld 669
69120 Heidelberg
Tel.: +49 6221-56-310561
manju.kumari(at)med.uni-heidelberg.de

Selected Publications

1. Suraj J. Patel, Nan Liu, Sam Piaker, Anton Gulko, Maynara L. Andrade, Frankie D. Heyward, Tyler Sermersheim, Nufar Edinger, Harini Srinivasan, Margo P. Emont, Gregory P. Westcott, Jay Luther, Raymond T. Chung, Shuai Yan, Manju Kumari, Reeby Thomas, Yann Deleye, André Tchernof, Phillip J. White, Guido A. Baselli, Marica Meroni, Dario F. De Jesus, Rasheed Ahmad, Rohit N. Kulkarni, Luca Valenti, Linus Tsai, Evan D. Rosen. Hepatic IRF3 fuels dysglycemia in obesity through direct regulation of Ppp2r1b. Sci. Transl. Med. 2022; March 23:14, eabh3831. DOI: 10.1126/scitranslmed.abh383
2. Yan S, Kumari M, Xiao H, Jacobs C, Kochumon K, Jedrychowski M, Chouchani E, Ahmad R, Rosen ED. IRF3 reduces adipose thermogenesis via ISG15-mediated reprogramming of glycolysis. J Clin Invest. 2021; Apr 1: 131(7):e144888.doi.1172/JCI144888.
3. Roh CH, Kumari M, Taleb S, Tenen D, Jacobs C, Lyubetskaya A, Tsai L, Rosen ED. Adipocytes Fail to Maintain Cellular Identity During Obesity Due to Reduced PPARγ Activity and Elevated TGFβ-SMAD Signaling. Mol Metab. 2020;Dec 42;101086.doi:10.1016/j.molmet.2020.101086.
4. Tian T, Heine M, Evangelakos I, Schaltenberg N, Stähler T, Koch-Nolte F, Kumari M*, Heeren J*. The P2X7 ion channel is dispensable for energy and metabolic homeostasis of white and brown adipose tissues. Purinergic Signal. 2020; Oct 6; doi: 10.1007/s11302-020-09738-7.  *co-corresponding author
5. Roh HC, Tsai LTY, Shao M, Tenen D, Shen Y, Kumari M, Lyubetskaya A, Jacobs C, Dawes B, Gupta RK, Rosen ED. Warming Induces Significant Reprogramming of Beige, but Not Brown, Adipocyte Cellular Identity. Cell Metab. 2018; 27:1121-1137.
6. Kazak L, Chouchani ET, Lu GZ, Jedrychowski MP, Bare CJ, Mina AI, Kumari M, Zhang S, Vuckovic I, Laznik-Bogoslavski D, Dzeja P, Banks AS, Rosen ED, Spiegelman BM. Genetic Depletion of Adipocyte Creatine Metabolism Inhibits Diet-Induced Thermogenesis and Drives Obesity. Cell Metab. 2017; 26:660-671.
7. Shen Y, Roh CH, Kumari M, Rosen ED. Adipocyte glucocorticoid receptor is important in lipolysis and insulin resistance due to exogenous steroids, but not insulin resistance caused by high fat feeding. Mol Metab. 2017; 6:1150-1160.
8. Roh CH, Tsai L, Lyubetskaya A, Tenen D, Kumari M, Rosen ED. Simultaneous transcriptional and epigenomic profiling from specific cell types within heterogeneous tissues in vivo. Cell Reports. 2017. (18) 1048-1061.
9. *Kumari M, Wang X, Lantier L, Lyubetskaya A, Eguchi J, Kang S, Tenen D, Roh HC, Kong X, Kazak L, Ahmad R, Rosen ED. IRF3 promotes adipose inflammation and insulin resistance and represses browning. J Clin Invest. 2016; 126:2839-2854.
   *Research highlight in Nature Immunology, Aug 2016 issue.
10.  Folick A, Oakley HD, Yu Y, Armstrong EH, Kumari M, Sanor L, Moore DD, Ortlund EA, Zechner R, Wang MC. Lysosomal signaling molecules regulate longevity in Caenorhabditis elegans. Science. 2015; 347:83-86.
11. Pollak NM, Schweiger M, Jaeger D, Kolb D, Kumari M, Schreiber R, Kolleritsch S, Markolin P, Grabner GF, Heier C, Zierler KA, Rülicke T, Zimmermann R, Lass A, Zechner R, Haemmerle G. Cardiac-specific overexpression of perilipin 5 provokes severe cardiac steatosis via the formation of a lipolytic barrier. J Lipid Res. 2013; 54:1092-1102.
12. Kumari M, Schoiswohl G, Chitraju C, Paar M, Cornaciu I, Rangrez AY, Wongsiriroj N, Nagy HM, Ivanova PT, Scott SA, Knittelfelder O, Rechberger GN, Birner-G R, Eder S, Brown HA, Haemmerle G, Oberer M, Lass A, Kershaw EE, Zimmermann R & Zechner R. Adiponutrin functions as a nutritionally regulated lysophosphatidic acid acyltransferase. Cell Metab 15: 691-702, 2012
13. Haemmerle G, Moustafa T, Woelkart G, Büttner S, Schmidt A, van de Weijer T, Hesselink M, Jaeger D, Kienesberger PC, Zierler K, Schreiber R, Eichmann T, Kolb D, Kotzbeck P, Schweiger M, Kumari M, Eder S, Schoiswohl G, Wongsiriroj N, Pollak NM, Radner FP, Preiss-Landl K, Kolbe T, Rülicke T, Pieske B, Trauner M, Lass A, Zimmermann R, Hoefler G, Cinti S, Kershaw EE, Schrauwen P, Madeo F, Mayer B, Zechner R. ATGL-mediated fat catabolism regulates cardiac mitochondrial function via PPARα and PGC-1. Nat Med. 2011; 17:1076-1085.