Sudden cardiac death claims the lives of approximately 350,000 Americans each year. Nearly 50% of all coronary deaths are sudden, occurring within 1 hour of the onset of symptoms. Sudden cardiac death is most often due to cardiac arrhythmias such as long QT (LQTS), short QT (SQTS) and Brugada (BrS) syndromes and has significant social and economical consequences. The development of safe and effective therapeutic approaches has been hampered by the absence of an appropriate human in vitro model relevant to genetic arrhythmias.

My work focuses on establishing human arrhythmic in vitro model to gain more pathophysiological insights into different life threatening arrhythmic cardiac diseases. To generate the in vitro arrhythmic human model, we apply the recent breakthrough discovery of induced pluripotent stem cells (iPS cells) by reprogramming adult somatic cells into a pluripotent embryonic stem cell fate with the help of various extrinsic and intrinsic transcriptional factors such as Oct4, Sox2, Klf4 and c-myc.

Skin Biopsy fibroblasts or blood lymphocytes isolated from arrhythmic patients will be genetically reprogrammed into induced pluripotent stem cells (iPS cells) which are capable of being differentiated into various organ specific cell types including cardiomyocytes. Cardiomyocytes obtained from these iPS cells will serve as a relevant human in vitro model for the respective in vivo genetic arrhythmias. Much more importantly, this optimal in vitro model will contribute to develop novel anti-arrhythmic drugs for the efficient therapeutic management and cure of the cardiac arrhythmias.

Doss MX, Koehler CI, Gissel C, Hescheler J, Sachinidis A. “Embryonic stem cells: a promising tool for cell replacement therapy”. Journal of Cellular and Molecular Medicine;8(4):465-73, 2004. PubMed ID: 15601575

Gissel C, Voolstra C, Doss MX, Koehler CI, Winkler J, Hescheler J, Sachinidis A. “An optimized embryonic stem cell model for consistent gene expression and developmental studies: a fundamental study”. Thrombosis and Haemostosis;94(4):719-27, 2005. PubMed ID: 16270623

Doss MX, Potta SP, Hescheler J, Sachinidis A. “Trapping of growth factors by catechins: a possible therapeutical target for prevention of proliferative diseases”. Journal of Nutritional Biochemistry;16(5):259-66, 2005. PubMed ID: 15866224

Gissel C, Doss MX, Hippler-Altenburg R, Hescheler J, Sachinidis A. “Generation and characterization of cardiomyocytes under serum-free conditions”. Methods in Molecular Biology;330:191-219, 2006. PubMed ID: 16846026

Mariappan D, Winkler J, Parthiban V, Doss MX, Hescheler J, Sachinidis A. Dietary small molecules and large-scale gene expression studies: an experimental approach for understanding their beneficial effects on the development of malignant and non-malignant proliferative diseases. Curr Med Chem. 13(13):1481-9. 2006. PubMed ID: 16787199

Doss MX, Winkler J, Chen S, Hippler-Altenburg R, Sotiriadou I, Halbach M, Pfannkuche K, Liang H, Schulz H, Hummel O, Hübner N, Rottscheidt R, Hescheler J, Sachinidis A “Global transcriptome analysis of murine embryonic stem cells derived cardiomyocytes.” Genome Biolog;8(4):R56, 2007. PubMed ID: 17428332

Doss MX, Chen S, Winkler J, Hippler-Altenburg R, Odenthal M, Wickenhauser C, Balaraman S, Schulz H, Hummel O, Hübner N, Ghosh-Choudhury N, Sotiriadou I, Hescheler J, Sachinidis A. “Transcriptomic and phenotypic analysis of embryonic stem cell derived BMP2+ lineage cells: an insight into mesodermal patterning” Genome Biology; 8(9):R184, 2007. PubMed ID: 17784959

Doss MX, Sachinidis A, and Hescheler J “Human ES Cell Derived Cardiomyocytes for Cell Replacement Therapy: A Current Update” Chinese Journal of Physiology 51(4): 1-4, 2008. PubMed ID: 19112880

Pfannkuche K, Wunderlich FT, Doss MX, Spitkovsky D, Reppel M, Sachinidis A, Hescheler J. “Generation of a double-fluorescent double-selectable Cre/loxP indicator vector for monitoring of intracellular recombination events.” Nat Protoc.;3(9):1510-26, 2008. PubMed ID: 18772879

Akasha AA, Sotiriadou I, Doss MX, Halbach M, Winkler J, Baunach JJ, Katsen-Globa A, Zimmermann H, Choo Y, Hescheler J, Sachinidis A.” Entrapment of embryonic stem cells-derived cardiomyocytes in macroporous biodegradable microspheres: preparation and characterization” Cell Physiol Biochem.;22(5-6):665-72, 2008. PubMed ID: 19088448

Aksoy I, Bourillot P, Schreiber V, Schültz H, Hümmel O, Nolden T, Doss MX, Hübner N, Himmelbauer H, Sachinidis A, Hescheler J and Savatier P “Novel STAT3 target genes, including Klf4 and Klf5, exert distinct roles in the inhibition of mesoderm and endoderm differentiation in embryonic stem cells” PLoS Biology (in revision), 2009. PubMed ID: 19088448

Potta SP, Liang H, Pfannkuche K, Winkler J, Chen S, Doss MX, Obernier K, Kamisetti K, Schulz H, Hescheler J and Sachinidis A “Functional characterization and global transcriptome analysis of contractile smooth muscles cells derived from a murine transgenic Acta2 embryonic stem cell lineage” Hypertension;53(2):196-204, 2009. PubMed ID: 19064816

Trouillas M, Saucourt C, Guillotin B, Gauthereau X, Ding L, Buchholz F, Doss MX, Sachinidis A, Hescheler J, Hummel O, Hubner N, Kolde R, Vilo J, Schulz H and Bœuf H “Three LIF-dependent signatures and “competency genes” identified by gene profiling studies in mouse ES cells and early derivatives” BMC Genomics:10:73, 2009. PubMed ID: 19203379

Ding L, Paszkowski-Rogacz M, Nitzsche A, Slabicki MM, Heninger AK, Vries ID, Kittler R, Junqueira M, Shevchenko A, Schulz H, Hubner N, Doss MX, Sachinidis A, Hescheler J, Iacone R, Anastassiadis K, Stewart AF, Pisabarro MT, Caldarelli A, Poser I, Theis M, Buchholz F. “A Genome-Scale RNAi Screen for Oct4 Modulators Defines a Role of the Paf1 Complex for Embryonic Stem Cell Identity” Cell Stem Cell.:4(5):403-15, 2009. PubMed ID: 19345177

Schulz H, Kolde R, Adler P, Aksoy I, Anastassiadis K, Bader M, Billon N, Boeuf H, Bourillot PY, Buchholz F, Dani C, Doss MX, Forrester L, Gitton M, Henrique D, Hescheler J, Himmelbauer H, Hübner N, Karantzali E, Kretsovali A, Lubitz S, Pradier L, Rai M, Reimand J, Rolletschek A, Sachinidis A, Savatier P, Stewart F, Storm MP, Trouillas M, Vilo J, Welham MJ, Winkler J, Wobus AM, Hatzopoulos AK; Functional Genomics in Embryonic Stem Cells Consortium. "The FunGenES database: a genomics resource for mouse embryonic stem cell differentiation".PLoS One. 2009 Sep 3;4(9):e6804. PubMed ID: 19727443

Gunaseeli I, Doss MX, Hescheler J, Sachinidis A "Induced Pluripotent Stem (iPS) Cells as a Model for Accelerating Drug Discovery". Current Medicinal Chemistry (in press)

Doss MX, Wagh V, Schulz H, Kull M, Kolde R, Pfannkuche K, Nolden T, Himmelbauer H, Vilo J, Hescheler J, Sachinidis A: "Global Transcriptomic Analysis of Murine ESC Derived Brachyury+ (T) Cells" Genes to Cells (in press)

Šaric T, Chen S, Kamisseti N, Halbach M, Doss MX, Winkler J, Hescheler J and Sachinidis A “Embryonic Stem Cells and Their Therapeutic Potential” 2008 "Handbook of Cardiac Stem Cell Therapy" (edited by Ioannis Dimarakis et al.)