This Fellowship is awarded for a period of two years to early career clinician scientists undergoing medical specialist training with a strong interest in molecular medicine research topics. The fellows are integrated within the clinical setting of the Medical Faculty and aim at doing research at the interface of medicine and basic molecular biology and have the opportunity to work at a laboratory at the medical campus (e.g. OMZ) or at the EMBL. The fellows conduct their research in collaboration with a matching EMBL group.
CDF awardee February 2015:
Johannes Pfeil, MD
Johannes is a physician for Pediatric Rheumatology and Infectious Diseases at the Hospital for Children and Adolescents of Heidelberg University(General Pediatrics).
2007 MD thesis, University Heidelberg
Residency in General Pediatrics, University of Würzburg, Germany (2007-2008)
Physician at the Center for Childhood and Adolescent Medicine (General Pediatrics), University Hospital Heidelberg, since 2008
Board certification in General Pediatrics, 2012
Board certification Pediatric Rheumatology, 2014
Board certification Infectious Diseases, 2015
HRCMM Career Development Fellowship, since 2015.
Clinical host: Dr. Ann-Kristin Müller, Center for Infectious Diseases, Parasitology Unit, University Hospital Heidelberg
EMBL host: Dr. Jeroen Krijgsveld, Genome Biology
Disease studied: Malaria
Malaria, a parasite infection of red blood cells, kills roughly 2000 people per day, most of whom are children in Africa. In experimental immunization trials, intravenous administration of whole attenuated malaria parasites successfully protected humans against wild-type malaria infection. Even though this concept is unfeasible for direct translation towards routine vaccination, it still serves as a model to investigate protective immune responses against malaria.
By applying advanced mass spectrometric analysis, Johannes wants to identify critical targets of protective immunity induced by whole-parasite immunization at the very early and clinically silent malaria liver stage. The successful identification of these targets may provide the basis for future development of highly protective subunit malaria vaccines.
CDF awardee 2014:
Sascha Dietrich, MD
Sascha is physician undergoing specialty training for Hematology and Oncology in the Department of Hematology, Oncology and Rheumatology at the University Medical Center for Internal Medicine, Heidelberg.
2007 MD thesis, University of Jena.
Residency in Internal Medicine and Hematology at Heidelberg University Hospital, since 2006.
Emergency medicine board certification, since 2011.
HRCMM Career Development Fellowship, since 2014.
Clinical hosts: Anthony D. Ho, Department of Internal Medicine V: Hematology, Oncology and Rheumatology, Heidelberg University Hospital
Thorsten Zenz, Department of Translational Oncology, Section Lymphoma Research, National Center for Tumor Diseases (NCT) Heidelberg
EMBL host: Wolfgang Huber, Genome Biology
Disease studied: Hematologic cancers, lympho- proliferative diseases (LPD)
Most cancer patients are treated with chemotherapy irrespective of diverse biology, but the discovery of key pathogenetic mutations has already transformed the treatment of specific cancer types. Successful examples of hematologic cancers include BCR-ABL inhibition of chronic myeloid leukaemia and as recently published by us, BRAF inhibition in hairy cell leukaemia.
We are aiming to understand the functional role of critical signalling pathways in lympho- proliferative diseases (LPD) and to determine the biological basis for differential response to genotype specific treatment. Pathway sensitivity and resistance of primary human tumour cells will be systematically mapped ex vivo using large and diverse compound libraries (up to 2500 compounds) across leukaemia s and lymphoma subtypes (refractory CLL, T-PLL, B-PLL, MCL, LPL, FL) to functionally group patients according to drug sensitivities. Paired with detailed molecular characterization of all tumour samples, and available clinical follow-up of the same patients, this novel and innovative approach provides unique opportunities to identify key pathways that determine sensitivity to specific drugs and drug combinations with the immediate potential for clinical translation.
CDF awardees 2013:
Joachim Kunz, MD
Joachim is an attending physician for Pediatric Hematology and Oncology in the Department of Pediatric Oncology, Hematology, Immunology and Pulmonology at the Hospital for Children and Adolescents of Heidelberg University.
2002 MD thesis, approbation/license to practice medicine, University of Tübingen.
Medical specialist in pediatric hematology and oncology, University Medical Center for Children and Adolescents, Heidelberg, since 2009.
Attending physician in pediatric hematology and oncology, University Medical Center for Children and Adolescents, Heidelberg, since 2013.
HRCMM Career Development Fellowship since 2013.
Clinical host: Andreas E. Kulozik, Department of Pediatric Oncology, Hematology, Immunology and Pulmonology
University Medical Center for Children and Adolescents, Heidelberg
EMBL host: Jan Korbel, Genome Biology
Disease studied: T-cell acute lymphoblastic leukemia (T-ALL) in children
Leukemia is the most common malignancy in childhood. T-ALL accounts for approximately 15% of all ALL in children and adolescents. Whereas the primary T-ALL can be cured in more than 80% of patients with current treatment protocols, relapsed T-ALL is almost invariably fatal: during the time between first diagnosis and relapse, T-ALL evolves into a resistant disease by acquiring new mutations induced by chemotherapy and by selection of subclones. Using whole exome sequencing, Joachim hopes to find mechanisms of treatment resistance and understand the evolution of T-ALL during a patient’s course of disease.
The activating STAT5B N642H mutation is a common abnormality in pediatric T-cell acute lymphoblastic leukemia and confers a higher risk of relapse.
Bandapalli OR, Schuessele S, Kunz JB, Rausch T, Stütz AM, Tal N, Geron I, Gershman N, Izraeli S, Eilers J, Vaezipour N, Kirschner-Schwabe R, Hof J, von Stackelberg A, Schrappe M, Stanulla M, Zimmermann M, Koehler R, Avigad S, Handgretinger R, Frismantas V, Bourquin JP, Bornhauser B, Korbel JO, Muckenthaler MU, Kulozik AE.
Haematologica. 2014 Oct;99(10):e188-92. doi: 10.3324/haematol.2014.104992. Epub 2014 Jun 27.
Pädiatrie 4. Auflage
Kunz J, Kulozik A
Kap 178 Erythrozyten,2014, S 1429-56 Hrsg: Hoffmann, Lentze, Spranger, Zepp: Springer ISBN 978-3-642-41865-5
Lorenz Lehmann, MD
Lorenz is a physician for Cardiology in the Department of Cardiology, Angiology and Pulmonology, at the University Medical Center for Internal Medicine, Heidelberg.
2006 MD thesis, University of Heidelberg.
Physician undertaking specialty training at the Department of Cardiology, Angiology and Pulmonology, University Hospital Heidelberg, since 2007.
Research fellow in experimental cardiology, Johannes Backs lab, University of Heidelberg, since 2007.
HRCMM Career Development Fellowship since 2013.
Clinical host: Hugo A. Katus, Department of Cardiology, Angiology and Pulmonology, University Hospital Heidelberg
EMBL host: Eileen Furlong, Genome Biology
Disease studied: Heart failure
Research focus: Heart failure is one of the main causes of death in the western world. Previously, histone deacetylase 4 (HDAC4) was identified as a cardioprotective factor. Understanding the molecular basis of its posttranslational modifications enabled the development of potential therapeutic tools for the treatment of heart diseases. For instance, the N-terminal part of HDAC4 inhibits specific transcription factors such as MEF2, which is one of the key regulators for pathological cardiac remodeling which leads ultimately to heart failure.
During the HRCMM project Lorenz aims to comprehensively identify MEF2 and HDAC4 regulated genes via ChIP-seq experiments. Subsequently, he will study their contribution to the transition from a healthy to a diseased heart. It is the overall goal to gain a deep understanding of the epigenetic modifications driven by HDAC4 and to identify epigenetic drug targets for cardioprotection.
Essential role of sympathetic endothelin A receptors for adverse cardiac remodeling.
Lehmann LH, Rostosky JS, Buss SJ, Kreusser MM, Krebs J, Mier W, Enseleit F, Spiger K, Hardt SE, Wieland T, Haass M, Lüscher TF, Schneider MD, Parlato R, Gröne HJ, Haberkorn U, Yanagisawa M, Katus HA, Backs J. Proc Natl Acad Sci U S A. 2014 Sep 2. pii: 201409026. [Epub ahead of print]
CaM Kinase II mediates maladaptive post-infarct remodeling and pro-inflammatory chemoattractant signaling but not acute myocardial ischemia/reperfusion injury.
Weinreuter M, Kreusser MM, Beckendorf J, Schreiter FC, Leuschner F, Lehmann LH, Hofmann KP, Rostosky JS, Diemert N, Xu C, Volz HC, Jungmann A, Nickel A, Sticht C, Gretz N, Maack C, Schneider MD, Gröne HJ, Müller OJ, Katus HA, Backs J. EMBO Mol Med. 2014 Sep 5. pii: e201403848. doi: 10.15252/emmm.201403848. [Epub ahead of print]
The Cardiac CaMKII Genes δ and γ Contribute Redundantly to Adverse Remodeling but Inhibit Calcineurin-Induced Myocardial Hypertrophy.
Kreusser MM, Lehmann LH, Keranov S, Hoting MO, Kohlhaas M, Reil JC, Neumann K, Schneider MD, Hill JA, Dobrev D, Maack C, Maier LS, Gröne HJ, Katus HA, Olson EN, Backs J.
Circulation. 2014 Aug 14. pii: CIRCULATIONAHA.114.006185. [Epub ahead of print] PMID:25124496
Depletion of globosides and isoglobosides fully reverts the morphologic phenotype of Fabry disease.
Porubsky S, Jennemann R, Lehmann L, Gröne HJ.
Cell Tissue Res. 2014 Jul 4. [Epub ahead of print]
Histone deacetylase signaling in cardioprotection.
Lehmann LH, Worst BC, Stanmore DA, Backs J.
Cell Mol Life Sci. 2013 Dec 6.
The role of endothelin-1 in the sympathetic nervous system in the heart.
Lehmann LH, Stanmore DA, Backs
J. Life Sci. 2014 Mar 13. pii: S0024-3205(14)00317-8. doi: 10.1016/j.lfs.2014.03.005. [Epub ahead of print] Review. PMID: 24632477
April 2013: Lorenz Lehmann receives Rudi Busse - Young Investigator Award for his work in experimental cardiovascular research.
Stephan Singer, MD
Stephan is a physician for Pathology in the Department of General Pathology at the Institute of Pathology Heidelberg, IPH.
2005 MD thesis, University of Heidelberg.
Physician undertaking specialty training at the Institute of Pathology, University Medical Center Heidelberg, since 2005.
2008 Postdoc Columbia University New York City, USA.
2011 Gerok fellowship SFB/TRR77.
HRCMM Career Development Fellowship since 2013.
Clinical host: Peter Schirmacher, Institute of Pathology Heidelberg
EMBL host: Martin Beck, Structural and Computational Biology
Disease studied: Liver cancer
Research focus: Hepatocellular carcinoma (HCC) is one of the most frequent malignancies world-wide with an increasing incidence and a poor prognosis. Signalling cascades of (hepato-)carcinogenic pathways pass the nuclear envelope through the nuclear pore complex (NPC). The NPC is a multiprotein complex spanning the nuclear envelope and consists of ~30 nucleoporins (Nups). The project investigates compositional changes of the NPC occurring in the process of hepatocarcinogenesis and to what extent NPC remodelling modulates liver cancer-relevant pathways. In collaboration with the Beck lab (EMBL) Stephan will address this in vitro and in vivo by using targeted and non-targeted mass spectrometry, gene expression arrays, cell-based assays, murine HCC models, and human HCC samples. Tumour-specific alterations of the NPC may provide the basis for novel therapeutic approaches.
Overexpression of far upstream element (FUSE) binding protein (FBP)-interacting repressor (FIR) supports growth of hepatocellular carcinoma
Malz, M., Bovet, M., Samarin, J., Rabenhorst, U., Sticht, C., Bissinger, M., Roessler, S., Lorenzo Bermejo, J., Renner, M., Calvisi, D. F., Singer, S., Ganzinger, M., Weber, A., Gretz, N., Zornig, M., Schirmacher, P., and Breuhahn, K.
Hepatology 60,1241-50, 2014
Prosurvival function of the cellular apoptosis susceptibility/importin-α1 transport cycle is repressed by p53 in liver cancer.
Winkler J1, Ori A, Holzer K, Sticht C, Dauch D, Eiteneuer EM, Pinna F, Geffers R, Ehemann V, Andres-Pons A, Breuhahn K, Longerich T, Lorenzo Bermejo J, Gretz N, Zender L, Schirmacher P, Beck M, Singer S.
Hepatology. 2014 May 6. doi: 10.1002/hep.27207. [Epub ahead of print]
July 2014: Stephan Singer receives the Hella-Bühler-Award for his outstanding work in cancer research.