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          About NIAMS
          Jens Kalchschmidt, Ph.D.





Jens Kalchschmidt, Ph.D.


Research Fellow
    Laboratory of Molecular Immunogenetics, Genomics and Immunity Section Image
              Headshot Jens 
            Contact Information

                                                  301-451-7422
                
                                                9000 Rockville Pike
                  
            10 Center Drive
      
                  
            Building 10, Room 13C120
      
                                   Bethesda MD 20892
                
                                                kalchschmidtjs@mail.nih.gov 
                                          Media Resources
                                  
            High Resolution Image 
                Summary
          Jens Kalchschmidt, Ph.D., studied molecular biotechnology at the University of Heidelberg before joining the trinational study course at the Ecole Supérieure de Biotechnologie de Strasbourg. For his master's thesis, he worked in the target identification and validation unit for cancer research at the Novartis Institutes for Biomedical Research in Basel. Dr. Kalchschmidt received a 1+3 Wellcome Trust Ph.D. fellowship to join the Molecular and Cellular Basis of Infection program at Imperial College London and obtained his Ph.D. in the laboratory of Professor Martin Allday, studying gene regulation by Epstein-Barr virus nuclear antigen 3C. For his postdoctoral work, Dr. Kalchschmidt joined the laboratory of Dr. Rafael Casellas at the NIAMS, where he studies the mammalian Mediator complex and sets up CRISPR/Cas9 screens to dissect gene regulatory networks in human B cells.He aims to understand B cell regulatory mechanisms better and identify novel therapeutic targets for B cell lymphoma.
        
                  Research Statement
          
            During his Ph.D in the laboratory of Professor Martin Allday, Dr. Kalchschmidt investigated the molecular mechanisms by which Epstein-Barr virus nuclear antigen 3C (EBNA3C) regulates host gene expression.****Intrigued by the fact that EBNA3C can act as either activator or repressor of its target genes, he chose to study the most upregulated gene (*AICDA*) and the three most repressed genes (*COBLL1*, *ADAM28,* and *ADAMDEC1*). Changes to histone modifications at these loci correlated well with gene expression and indicated a two-step mechanism for EBNA3C-mediated repression. Surprisingly, recruitment of a Polycomb protein, generally linked to gene repression, was observed at all four genes, irrespective of being activated or repressed by EBNA3C. Furthermore, unexpected recruitment of the DNA-binding transcription factor RBPJ at EBNA3C binding sites was detected only when EBNA3C was functional. This challenged existing models of how RBPJ, a repressive transcription factor of the Notch signaling pathway, functions in EBNA3C-mediated gene regulation. Furthermore, the direct activation of *AICDA* by EBNA3C may play a role in EBV-associated lymphoma as it encodes a B cell-specific protein required for somatic hypermutation and class switch recombination, but also causes off-target DNA damage that can result in B cell lymphomagenesis.

To follow his interest and broaden his expertise in gene regulation, Dr. Kalchschmidt joined Dr. Rafael Casellas’ lab at the NIAMS to study the role of the mammalian Mediator complex in gene regulation. Mediator, a large 33 subunit multi-protein complex conserved across eukaryotes, plays an integral part in eukaryotic gene expression. In collaboration with the laboratory of Dr. Francisco Asturias, he worked on the genetic, functional, and structural characterization of the mammalian Mediator complex. CRISPR/Cas9 gene targeting identified essential subunits required for cell survival and a set of nonessential subunits that, upon deletion, mostly affected genes regulated by multiple enhancers. Structural analysis revealed that most essential subunits form a conserved core similar to yeast Mediator. Nonessential subunits, some of which are mammalian specific, added to the structural complexity of the mammalian Mediator.

Contrary to current models that indicate Mediator acts as a topological bridge linking enhancers and promoters, depletion of Mediator does not alter genome architecture. Furthermore, conformational changes in Mediator were observed that increased interactions with RNA polymerase II. These results led to the proposal that the structural flexibility of Mediator enables it to integrate and relay regulatory signals between transcription factors and RNA polymerase II and that Mediator forms a functional, instead of an architectural, bridge linking enhancers and promoters. 

            Scientific Publications
              Structure of mammalian Mediator complex reveals Tail module architecture and interaction with a conserved core.

    Zhao H, Young N, Kalchschmidt J, Lieberman J, El Khattabi L, Casellas R, Asturias FJ
        

                    Nat Commun.
        
                    2021 Mar 1;
        
                    12(1).
        
                    doi: 10.1038/s41467-021-21601-w
                            PMID: 33649303
  A Pliable Mediator Acts as a Functional Rather Than an Architectural Bridge between Promoters and Enhancers.

    El Khattabi L, Zhao H, Kalchschmidt J, Young N, Jung S, Van Blerkom P, Kieffer-Kwon P, Kieffer-Kwon KR, Park S, Wang X, Krebs J, Tripathi S, Sakabe N, Sobreira DR, Huang SC, Rao SSP, Pruett N, Chauss D, Sadler E, Lopez A, Nóbrega MA, Aiden EL, Asturias FJ, Casellas R
        

                    Cell.
        
                    2019 Aug 22;
        
                    178(5).
        
                    doi: 10.1016/j.cell.2019.07.011
                            PMID: 31402173
  Plasmacytoid dendritic cells respond to Epstein-Barr virus infection with a distinct type I interferon subtype profile.

    Gujer C, Murer A, Müller A, Vanoaica D, Sutter K, Jacque E, Fournier N, Kalchschmidt J, Zbinden A, Capaul R, Dzionek A, Mondon P, Dittmer U, Münz C
        

                    Blood Adv.
        
                    2019 Apr 9;
        
                    3(7).
        
                    doi: 10.1182/bloodadvances.2018025536
                            PMID: 30952679
  EBV persistence without its EBNA3A and 3C oncogenes in vivo.

    Murer A, McHugh D, Caduff N, Kalchschmidt J, Barros M, Zbinden A, Capaul R, Niedobitek G, Allday M, Chijioke O, Münz C
        

                    PLoS Pathog.
        
                    2018 Apr;
        
                    14(4).
        
                    doi: 10.1371/journal.ppat.1007039
                            PMID: 29709016
  Epstein-Barr virus nuclear protein EBNA3C directly induces expression of AID and somatic mutations in B cells.

    Kalchschmidt JS, Bashford-Rogers R, Paschos K, Gillman AC, Styles CT, Kellam P, Allday MJ
        

                    J Exp Med.
        
                    2016 May 30;
        
                    213(6).
        
                    doi: 10.1084/jem.20160120
                            PMID: 27217538
  EBNA3C Directs Recruitment of RBPJ (CBF1) to Chromatin during the Process of Gene Repression in EBV Infected B Cells.

    Kalchschmidt JS, Gillman AC, Paschos K, Bazot Q, Kempkes B, Allday MJ
        

                    PLoS Pathog.
        
                    2016 Jan;
        
                    12(1).
        
                    doi: 10.1371/journal.ppat.1005383
                            PMID: 26751214
  Epstein-Barr Virus Proteins EBNA3A and EBNA3C Together Induce Expression of the Oncogenic MicroRNA Cluster miR-221/miR-222 and Ablate Expression of Its Target p57KIP2.

    Bazot Q, Paschos K, Skalska L, Kalchschmidt JS, Parker GA, Allday MJ
        

                    PLoS Pathog.
        
                    2015 Jul;
        
                    11(7).
        
                    doi: 10.1371/journal.ppat.1005031
                            PMID: 26153983
  In vivo time-lapse imaging shows diverse niche engagement by quiescent and naturally activated hematopoietic stem cells.

    Rashidi NM, Scott MK, Scherf N, Krinner A, Kalchschmidt JS, Gounaris K, Selkirk ME, Roeder I, Lo Celso C
        

                    Blood.
        
                    2014 Jul 3;
        
                    124(1).
        
                    doi: 10.1182/blood-2013-10-534859
                            PMID: 24850759 
          Education
              
            **Imperial College London**
Ph.D. (2016)

**Imperial College London**
M.Res. (2012)

**Ecole Superieur de Biotechnologie de Strasbourg**
M.S. (2011)

**University of Strasbourg**
M.S. (2011)             
                        Experience
              
            **Research Fellow**
NIAMS (2021-present)

**Visiting Fellow**
NIAMS (2016-2021)


Last Updated: October 2022


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