Klinik und Poliklinik
für Innere Medizin II
Klinik und Poliklinik für Innere Medizin II
Direktor: Univ.-Prof. Dr. med. Roland. M. Schmid
direktion.med2@mri.tum.de

Arbeitsgruppe PD Dr. Maximilian Reichert

Unsere Arbeitsgruppe beschäftigt sich mit der Erforschung der Rolle epithelialer Plastizität in der Embryonalentwicklung, Regeneration und Tumorentstehung/-progression der Bauchspeicheldrüse sowie der Generierung von neuartigen Zellkultursystemen (z.B. Organoiden) von Patienten mit gastrointestinalen Tumorerkrankungen zur potentiellen Beurteilung von Prognose, Therapieansprechen und Resistenzen.

Team

  • PD Dr. med. Maximilian Reichert (Leitung)
  • Karin Feldmann, M.sc. (PhD candidate)
  • Dr. med. vet. Zahra Dantes, VMD, PhD (Postdoc)
  • Katja Peschke, M.sc. (PhD candidate)
  • Aristeidis Papargyriou, M.sc. (PhD candidate)
  • Raphela Ranjan, M.sc. (PhD candidate)
  • Arlett Schäfer (MD candidate)
  • Patrick Wustrow (MD candidate)

Forschungsgebiet

Die Arbeitsgruppe von Herrn PD Dr. Reichert beschäftigt sich mit der Rolle epithelialer Plastizität in der Embryonalentwicklung, Regeneration und Tumorentstehung/-progression der Bauchspeicheldrüse. Am Bespiel der Bauchspeicheldrüse werden zudem allgemeingültige Mechanismen von Tumorstreuung (Dissemination) sowie sekundärer Tumorformation (Kolonisierung und Metastasierung) erörtert. Letztlich ist es ein großes Anliegen der Gruppe, die gewonnenen Erkenntnisse in neuartige Therapiekonzepte umzusetzen.

englische Seite

Publikationen

  1. Reichert M, Saur D, Hamacher R, Schmid RM, Schneider G. Phosphoinositide-3-kinase signaling controls S-phase kinase-associated protein 2 transcription via E2F1 in pancreatic ductal adenocarcinoma cells. Cancer Res. 2007 May 1;67(9):4149-56.
  2. Kolb S, Fritsch R, Saur D, Reichert M, Schmid RM, Schneider G. HMGA1 controls transcription of insulin receptor to regulate cyclin D1 translation in pancreatic cancer cells. Cancer Research 2007;67(10):4679-86.
  3. Schneider G, Reichert M, Saur D, Hamacher R, Fritsch R, Schmid RM. HDAC3 is linked to cell cycle machinery in MiaPaCa2 cells by regulating transcription of skp2. Cell Proliferation 2007;40(4):522-31.
  4. Hamacher R, Saur D, Fritsch R, Reichert M, Schmid RM, Schneider G. Casein kinase II inhibition induces apoptosis in pancreatic cancer cells. Oncol Rep 2007;18(3):695-701.
  5. Schild C, Wirth M, Reichert M, Schmid RM, Saur D, Schneider G. PI3K signaling maintains c-myc expression to regulate transcription of E2F1 in pancreatic cancer cells. Mol Carcinog 2009
  6. Wescott MP, Rovira M, Reichert M, von Burstin J, Means A, Leach SD, Rustgi AK. Pancreatic Ductal Morphogenesis and the Pdx1 Homeodomain Transcription Factor. Mol Biol Cell 2009 Nov;20(22):4838-44
  7. von Burstin J, Reichert M, Wescott MP, Rustgi AK. The pancreatic and duodenal homeobox protein PDX-1 regulates the ductal specific keratin 19 through the degradation of MEIS1 and DNA binding. PLoS One. 2010 Aug 19;5(8).
  8. Pinho AV, Rooman I, Reichert M, De Medts N, Bouwens L, Rustgi AK, Real FX. Adult pancreatic acinar cells dedifferentiate to an embryonic progenitor phenotype with concomitant activation of a senescence program that is present in chronic pancreatitis. Gut. 2011 Jul;60(7):958-66. doi: 10.1136/gut.2010.225920. Epub 2010 Dec 30.
  9. Reichert M, Rustgi AK. Pancreatic ductal cells in development, regeneration, and neoplasia. J Clin Invest. 2011 Dec;121(12):4572-8. doi: 10.1172/JCI57131. Epub 2011 Dec 1. Review.
  10. Botta GP, Reginato MJ, Reichert M, Rustgi AK, Lelkes PI. Constitutive K-RasG12D activation of ERK2 specifically regulates 3D invasion of human pancreatic cancer cells via MMP-1. Mol Cancer Res. 2012 Feb;10(2):183-96. doi: 10.1158/1541-7786.MCR-11-0399. Epub 2011 Dec 8.
  11. Rhim AD, Mirek ET, Aiello NM, Maitra A, Bailey JM, McAllister F, Reichert M, Beatty GL, Rustgi AK, Vonderheide RH, Leach SD, Stanger BZ. EMT and dissemination precede pancreatic tumor formation. Cell. 2012 Jan 20;148(1-2):349-61. doi: 10.1016/j.cell.2011.11.025. (recommended by Faculty of 1000, comment in Cell 2012 and Nat. Rev. Cancer 2012)
  12. Conradt L, Henrich A, Wirth M, Reichert M, Lesina M, Algül H, Schmid RM, Krämer OH, Saur D, Schneider G. Mdm2 inhibitors synergize with topoisomerase II inhibitors to induce p53-independent pancreatic cancer cell death. Int J Cancer. 2013 May 15;132(10):2248-57. doi: 10.1002/ijc.27916. Epub 2012 Nov 26.
  13. Reichert M, Takano S, von Burstin J, Kim SB, Lee JS, Ihida-Stansbury K, Hahn C, Heeg S, Schneider G, Rhim AD, Stanger BZ, Rustgi AK. The Prrx1 homeodomain transcription factor plays a central role in pancreatic regeneration and carcinogenesis. Genes Dev. 2013 Feb 1;27(3):288-300. doi:10.1101/gad.204453.112. Epub 2013 Jan 25. (recommended by Faculty of 1000)
  14. Diersch S, Wenzel P, Szameitat M, Eser P, Paul MC, Seidler B, Eser S, Messer M, Reichert M, Pagel P, Esposito I, Schmid RM, Saur D, Schneider G. Efemp1 and p27Kip1 modulate responsiveness of pancreatic cancer cells towards a dual PI3K/mTOR inhibitor in preclinical models. Oncotarget. 2013 Feb;4(2):277-88.
  15. Botta GP, Reichert M, Reginato MJ, Heeg S, Rustgi AK, Lelkes PI. ERK2-regulated TIMP1 induces hyperproliferation of K-Ras(G12D)-transformed pancreatic ductal cells. Neoplasia. 2013 Apr;15(4):359-72.
  16. Reichert M, Takano S, Heeg S, Bakir B, Botta GP, Rustgi AK Gregory P. Botta, Anil K. Rustgi. Isolating Murine Pancreatic Ductal Cells using Magnetic Beads in Development, Regeneration and Cancer, Nature Protocols, 2013 Jun 20;8(7):1354-65. doi: 10.1038/nprot.2013.079.
  17. Kim J, Hoffman JP, Alpaugh RK, Rhim AD, Reichert M, Stanger BZ, Furth EE, Sepulveda AR, Yuan CX, Won KJ, Donahue G, Sands J, Gumbs AA, Zaret KS. An iPSC Line from Human Pancreatic Ductal Adenocarcinoma Undergoes Early to Invasive Stages of Pancreatic Cancer Progression. Cell Rep. 2013 Jun 19. doi:pii: S2211-1247(13)00269-6. 10.1016/j.celrep.2013.05.036. (Editor's choice Science 2013)
  18. Gao T, McKenna B, Li C, Reichert M, Nguyen J, Singh T, Yang C, Pannikar A, Doliba N, Edlund H, Matschinsky F, Stein R, Stanger BZ. Pdx1 maintains β-cell identity and function by repressing an a-cell identity. Cell Metabolism. 2014 Feb 4;19(2):259-71. doi: 10.1016/j.cmet.2013.12.002.
  19. Bhattacharya S, Katlinski KV, Reichert M, Takano S, Brice A, Zhao B, Yu Q, Zheng H, Carbone CJ, Katlinskaya YV, Leu NA, McCorkell KA, Srinivasan S, Girondo M, Rui H, May MJ, Avadhani NG, Rustgi AK, Fuchs SY. Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury. EMBO Mol Med, 2014 Jan 30.
  20. Worthley DL, Churchill M, Compton JT, Tailor Y, Rao M, Si Y, Levin D, Schwartz MG, Uygur A, Hayakawa Y, Gross S, Renz BW, Setlik W, Martinez AN, Chen X, Nizami S, Lee HG, Kang HP, Caldwell JM, Asfaha S, Westphalen CB, Graham T, Jin G, Nagar K, Wang H, Kheirbek MA, Kolhe A, Carpenter J, Glaire M, Nair A, Renders S, Manieri N, Muthupalani S, Fox JG, Reichert M, Giraud AS, Schwabe RF, Pradere JP, Walton K, Prakash A, Gumucio D, Rustgi AK, Stappenbeck TS, Friedman RA, Gershon MD, Sims P, Grikscheit T, Lee FY, Karsenty G, Mukherjee S, Wang TC. Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential. Cell. 2015 Jan 15;160(1-2):269-84. doi: 10.1016/j.cell.2014.11.042.
  21. von Burstin J, Diersch S, Schneider G, Reichert M, Rustgi AK, Schmid RM. Detection of Tumor Suppressor Genes in Cancer Development by a Novel shRNA-Based Method. Mol Cancer Res. 2015 May;13(5):863-9. doi: 10.1158/1541-7786.MCR-14-0709. Epub 2015 Feb 27. PMID: 25724428
  22. Reichert M, Rhim AD, Rustgi AK. Culturing primary mouse pancreatic ductal cells. Cold Spring Harb Protoc. 2015 Jun 1;2015(6):pdb.prot078279. doi: 10.1101/pdb.prot078279. PMID: 26034301
  23. Ferreira MJ, McKenna LB, Zhang J, Reichert M, Bakir B, Buza EL, Furth EE, Bogue CW, Rustgi AK, Kaestner KH. Spontaneous Pancreatitis Caused by Tissue-Specific Gene Ablation of Hhex in Mice. Cell Mol Gastroenterol Hepatol. 2015 Sep 1;1(5):550-569. PMID: 26740970
  24. Reichert M, Blume K, Kleger A, Hartmann D, von Figura G. Developmental Pathways Direct Pancreatic Cancer Initiation from Its Cellular Origin. Stem Cells Int. 2016; 2016:9298535. doi: 10.1155/2016/9298535. Epub 2015 Nov 22. Review. PMID: 26681957
  25. Takano S, Reichert M*, Bakir B, Das KK, Nishida T, Miyazaki M, Heeg S, Collins MA, Marchand B, Hicks PD, Maitra A, Rustgi AK*. Prrx1 isoform switching regulates pancreatic cancer invasion and metastatic colonization. Genes Dev. 2016 Jan 15;30(2):233-47. doi: 10.1101/gad.263327.115. PMID: 26773005 *Corresponding authors (highlighted in Nature Reviews Cancer)
  26. Westphalen CB, Takemoto Y, Tanaka T, Macchini M, Jiang Z, Renz BW, Chen X, Ormanns S, Nagar K, Tailor Y, May R, Cho Y, Asfaha S, Worthley DL, Hayakawa Y, Urbanska AM, Quante M, Reichert M, Broyde J, Subramaniam PS, Remotti H, Su GH, Rustgi AK, Friedman RA, Honig B, Califano A, Houchen CW, Olive KP, Wang TC. Dclk1 Defines Quiescent Pancreatic Progenitors that Promote Injury-Induced Regeneration and Tumorigenesis. Cell Stem Cell. 2016 Apr 7;18(4):441-55. doi: 10.1016/j.stem.2016.03.016. PMID: 27058937
  27. Lubeseder-Martellato C, Hidalgo-Sastre A, Hartmann C, Alexandrow K, Kamyabi-Moghaddam Z, Sipos B, Wirth M, Neff F, Reichert M, Heid I, Schneider G, Braren R, Schmid RM, Siveke JT. Membranous CD24 drives the epithelial phenotype of pancreatic cancer. Oncotarget. 2016 May 17. doi: 10.18632/oncotarget.9402. PMID: 27203385
  28. Heeg S, Das KK, Reichert M, Bakir B, Takano S, Caspers J, Aiello NM, Wu K, Neesse A, Maitra A, Iacobuzio-Donahue CA, Hicks P, Rustgi AK. ETS-Transcription Factor ETV1 Regulates Stromal Expansion and Metastasis in Pancreatic Cancer. Gastroenterology. 2016 Jun 16. pii: S0016-5085(16)34619-4. doi: 10.1053/j.gastro.2016.06.005. PMID: 27318148
  29. Diersch S, Wirth M, Schneeweis C, Jörs S, Geisler F, Siveke JT, Rad R, Schmid RM, Saur D, Rustgi AK, Reichert M, Schneider G. Kras(G12D) induces EGFR-MYC cross signaling in murine primary pancreatic ductal epithelial cells. Oncogene. 2016 Jul 21;35(29):3880-6. doi: 10.1038/onc.2015.437. Epub 2015 Nov 23. PMID: 26592448
  30. Schneeweis C, Wirth M, Saur D, Reichert M, Schneider G. Oncogenic KRAS and the EGFR loop in pancreatic carcinogenesis - a connection to licensing nodes. Small GTPases. 2016 Nov 23:0. [Epub ahead of print] PMID: 27880072
  31. Westphalen CB, Renz B, Reichert M, Rustgi AK, Wang TC. Cellular Plasticity and Heterogeneity in Pancreatic Regeneration and Malignancy. Cancer Cell & Microenvironment 2016; 3: e1472. doi: 10.14800/ccm.1472
  32. Renz BW, Takahashi R, Tanaka T, Macchini M, Hayakawa Y, Dantes Z, Maurer HC, Chen X, Jiang Z, Westphalen CB, Ilmer M, Valenti G, Mohanta SK, Habenicht AJR, Middelhoff M, Chu T, Nagar K, Tailor Y, Casadei R, Di Marco M, Kleespies A, Friedman RA, Remotti H, Reichert M, Worthley DL, Neumann J, Werner J, Iuga AC, Olive KP, Wang TC. β2 Adrenergic-Neurotrophin Feedforward Loop Promotes Pancreatic Cancer. Cancer Cell. 2017 Dec 1. pii: S1535-6108(17)30510-X. doi: 10.1016/j.ccell.2017.11.007. PMID: 29249692
  33. Hassan Z, Schneeweis C, Wirth M, Veltkamp C, Dantes Z, Feuerecker B, Ceyhan GO, Knauer SK, Weichert W, Schmid RM, Stauber R, Arlt A, Krämer OH, Rad R, Reichert M, Saur D, Schneider G. MTOR inhibitor-based combination therapies for pancreatic cancer. Br J Cancer. 2018 Feb 6;118(3):366-377. doi: 10.1038/bjc.2017.421.
  34. Das KK, Heeg S, Pitarresi JR, Reichert M, Bakir B, Takano S, Kopp JL, Wahl-Feuerstein A, Hicks P, Sander M, Rustgi AK. ETV5 regulates ductal morphogenesis with Sox9 and is critical for regeneration from pancreatitis. Dev Dyn. 2018 Mar 13. doi: 10.1002/dvdy.24626.
  35. Moreira L, Bakir B, Chatterji P, Dantes Z, Reichert M, Anil Rustgi AK. Pancreas 3D organoids: current and future aspects as a research platform for personalized medicine in pancreatic cancer. Cellular and Molecular Gastroenterology and Hepatology (CMGH). DOI: http://dx.doi.org/10.1016/j.jcmgh.2017.12.004
  36. Ruess DA, Heynen GJ, Ciecielski KJ, Ai J, Berninger A, Kabacaoglu D, Görgülü K, Dantes Z, Wörmann SM, Diakopoulos KN, Karpathaki AF, Kowalska M, Kaya-Aksoy E, Song L, van der Laan EAZ, López-Alberca MP, Nazaré M, Reichert M, Saur D, Erkan MM, Hopt UT, Sainz B Jr, Birchmeier W, Schmid RM, Lesina M, Algül H. Mutant KRAS-driven cancers depend on PTPN11/SHP2 phosphatase. Nat Med. 2018 Jul;24(7):954-960. doi: 10.1038/s41591-018-0024-8. Epub 2018 May 28.
  37. Reichert M*, Bakir B, Moreira L, Pitarresi JR, Feldmann K, Simon L, Suzuki K, Maddipati R, Rhim AD, Schlitter AM, Kriegsmann M, Weichert W, Wirth M, Schuck K, Schneider G, Saur D, Reynolds AB, Klein-Szanto AJ, Pehlivanoglu B, Memis B, Adsay NV, Rustgi AK*. Regulation of Epithelial Plasticity Determines Metastatic Organotropism in Pancreatic Cancer. Dev Cell. 2018 Jun 18;45(6):696-711.e8. doi: 10.1016/j.devcel.2018.05.025. *Corresponding authors
  38. Renz BW, Tanaka T, Sunagawa M, Takahashi R, Jiang Z, Macchini M, Dantes Z, Valenti G, White RA, Middelhoff MA, Ilmer M, Oberstein PE, Angele MK, Deng H, Hayakawa Y, Westphalen CB, Werner J, Remotti H, Reichert M, Tailor YH, Nagar K, Friedman RA, Iuga AC, Olive KP, Wang TC. Cholinergic Signaling via Muscarinic Receptors Directly and Indirectly Suppresses Pancreatic Tumorigenesis and Cancer Stemness. Cancer Discov. 2018 Sep 5. pii: CD-18-0046. doi: 10.1158/2159-8290.CD-18-0046.
  39. Marchand B, Pitarresi JR, Reichert M, Suzuki K, Laczkó D, Rustgi AK. PRRX1 isoforms cooperate with FOXM1 to regulate the DNA damage response in pancreatic cancer cells. Oncogene. 2019 Jan 31. doi: 10.1038/s41388-019-0725-6. PMID: 30705403
  40. Li H, Shi K, Reichert M, Lin K, Tselousov N, Braren R, Fu D, Schmid R, Li J, Menze B. Differential Diagnosis for Pancreatic Cysts in CT Scans Using Densely-Connected Convolutional Networks. Conf Proc IEEE Eng Med Biol Soc. 2019 Jul;2019:2095-2098. doi: 10.1109/EMBC.2019.8856745. PMID: 31946314
  41. Biederstädt A, Hassan Z, Schneeweis C, Schick M, Schneider L, Muckenhuber A, Hong Y, Siegers G, Nilsson L, Wirth M, Dantes Z, Steiger K, Schunck K, Langston S, Lenhof HP, Coluccio A, Orben F, Slawska J, Scherger A, Saur D, Müller S, Rad R, Weichert W, Nilsson J, Reichert M, Schneider G, Keller U. SUMO pathway inhibition targets an aggressive pancreatic cancer subtype. Gut. 2020 Jan 30. pii: gutjnl-2018-317856. doi: 10.1136/gutjnl-2018-317856. PMID: 32001555

 

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Wissenschaftliche Arbeiten

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Kontakt und Ansprechpartner

Leitung: PD Dr. med. Maximilian Reichert
Klinik und Poliklinik für Innere Medizin II
Klinikum rechts der Isar der TUM
Trogerstr. 32 (Raum 1.04), 81675 München
Tel.: (0 89) 41 40 - 27 45
Fax: (0 89) 41 40 - 24 69

E-Mail: maximilian.reichert@mri.tum.de