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Molecular Pathogenesis of B-cell Lymphomas and Mesotheliomas

The elucidation of molecular pathomechanisms in tumor development represents the prerequisite i) to understand the biological behavior of tumors and ii) to identify molecular markers and signatures of diagnostic and prognostic value that allow stratification of patients for risk-adapted therapy decisions.
My research work focusses on the analysis of B-cell non-Hodgkin lymphomas. During the past years it resulted in the isolation of several genes (i.a. ATM) that are involved in the pathogenesis of B-cell chronic lymphocytic leukemia and mantle cell lymphoma. Currently, my work in the research group of the Institute of Clinical Pathology concentrates on the molecular pathogenesis of follicular lymphoma (FL). FL, one of the most common lymphomas in adults in Western countries, is an incurable disease, and its pathogenesis is only partly understood. Because of its highly variable clinical course the treatment of FL is one of the most controversial topics in oncology. The aim of our current study is to develop an accurate gene expression-based survival model for patients with FL that is applicable in a routine diagnostic setting to stratify the patients for risk-adapted therapy. For this purpose, the expression of genes (selected on the basis of microarray expression data) will be analyzed and correlated with clinical data. In a further study, we are investigating the molecular pathomechanisms of malignant mesotheliomas (genomic abberations; structural, epigenetic alterations and expression of candidate genes). This study is aimed at the isolation of i) pathogenically relevant alterations and ii) diagnostic markers that allow for the molecular distinction between mesotheliomas and other tumors residing in the lung (lung carcinoma, metastases).
 
Major Projects
  • Gene expression-based survival model for patients with follicular lymphoma
  • Pathogenically relevant alterations and diagnostic markers in malignant mesotheliomas
Dr. Claudia Kalla

phone: ++49-711-8101 5756

Selected References
  • Kalla C, Scheuermann MO, Kube I, Schlotter M, Mertens D, Döhner H, Stilgenbauer S, Lichter P. (2007) Analysis of 11q22-q23 deletion target genes in B-cell chronic lymphocytic leukaemia: evidence for a pathogenic role of NPAT, CUL5, and PPP2R1B. European Journal of Cancer 43(8):1328-35.
  • Briani C, Schlotter M, Lichter P, Kalla C. (2006) Development of a mantle cell lymphoma in an ATM heterozygous woman after occupational exposure to ionising radiation and somatic mutation of the second allele. Leukemia Research 30(9):1193-6.
  • Kalla C, Nentwich H, Schlotter M, Mertens D, Wildenberger K, Döhner H, Stilgenbauer S, Lichter P. (2005) Translocation t(X;11)(q13;q23) in B-cell chronic lymphocytic leukemia disrupts two novel genes. Genes Chromosomes Cancer 42(2):128-43.
  • Bridger JM, Kalla C, Wodrich H, Weitz S, King J, Khazai K, Kräusslich H-G, Lichter P. (2005) Nuclear RNAs confined to a reticular compartment between chromosome territories. Experimental Cell Research 302(2):180-93.
  • Mertens D, Wolf S, Schroeter P, Schaffner C, Döhner H, Stilgenbauer S, Lichter P. (2002) Down-regulation of candidate tumor suppressor genes within chromosome band 13q14.3 is independent of the DNA methylation pattern in B-cell chronic lymphocytic leukemia. Blood 99(11):4116-21.
  • Schaffner C, Idler I, Stilgenbauer S, Döhner H, Lichter P.2000) Mantle cell lymphoma is characterized by inactivation of the ATM gene. Proc Natl Acad Sci U S A 97(6):2773-8.
  • Schaffner C, Stilgenbauer S, Rappold GA, Döhner H, Lichter P. (1999) Somatic ATM mutations indicate a pathogenic role of ATM in B-cell chronic lymphocytic leukemia. Blood 94(2):748-53.
  • Stilgenbauer S*, Schaffner C*, Litterst A, Liebisch P, Gilad S, Bar-Shira A, James MR, Lichter P, Döhner H. (1997) Biallelic mutations in the ATM gene in T-prolymphocytic leukemia. Nature Medicine 3(10):1155-9. * gemeinsame Erstautorenschaft
Major Networks and Collaborations
  • 1996 - present: Prof. H. Döhner, Prof. S. Stilgenbauer, Department of Internal Medicine III, University of Ulm
  • 2009 – present: Prof. P. Lichter, German Cancer Research Center (DKFZ), Heidelberg
Extramural Funding
  • 1996: Leopoldina-Förderstipendium
  • 2004 – 2006: Deutsche Krebshilfe „Identifizierung pathogenetisch relevanter Gene in den chromosomalen Banden 11q22-q23 bei der chronisch lymphatischen Leukämie des B-Zell-Typs“
  • 2008 – 2010: Wilhelm-Sander-Stiftung „Molekularbiologische Untersuchungen zur Funktion des BRWD3-Gens und dessen Bedeutung für die Pathogenese der chronisch-lymphatischen Leukämie des B-Zell-Typs

Curriculum Vitae Claudia Kalla, PhD

Affiliation
Post doctoral scientist
Research Group of the Institute of Pathology, Robert Bosch Hospital

Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology
Auerbachstr. 112
D - 70376 Stuttgart Germany
phone: ++49-711-8101 5756
fax: ++49-711-859295
email: claudia.kalla@ikp-stuttgart.de
Education and Professional Career
1985 – 1990 Study of Biology, Martin Luther University Halle-Wittenberg
1990 Diploma degree for biology, field of specialization: genetics
1990-1995 PhD student, Institute of Genetics, University Halle-Wittenberg
1995-1996 Principle researcher, Institute of Human Genetics, University Halle-Wittenberg
1996 Doctor’s degree for natural sciences (PhD), Institute of Genetics, University Halle-Wittenberg
1996 Leopoldina-Förderstipendium, principle researcher at the German Cancer Research Center (DKFZ) Heidelberg
1996-2009 Post doctoral scientist at the DKFZ Heidelberg, Division of Molecular Genetics (Head Prof. P. Lichter)
1/2010 - present Post doctoral scientist at the Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart Research Group of the Institute of Clinical Pathology, Robert Bosch Hospital, Stuttgart (Head Prof. G. Ott)
Professional Memberships
1992-1998: Deutsche Botanische Gesellschaft
Since 1997: European Association for Cancer Research (EACR)