contact information:  telse@umich.edu

Curriculum Vitae

1992-2000 Medical Studies at the University of Hamburg/Germany and the Leopold Franzens University of Innsbruck/Austria

1995-2000 Doctoral Thesis at the Institute for Hormone and Fertility Research at the University of Hamburg: ‘Molecular determinants of Glucocorticoid Action in the Immune System’

2001-2003 Clinical Training at the University Hospital of Hamburg Eppendorf/Germany

2003-current Postdoctoral Research Fellow Metabolism, Endocrinology and Diabetes, Dept. of Internal Medicine, University of Michigan Health System, Ann Arbor, USA

1995-2000 Scholarship through the ‘Studienstiftung des Deutschen Volkes’

2003-2005 Scholarship through the ‘Deutsche Forschungsgemeinschaft’: The role of AgRP in adrenocortical steroidogenesis and organ maintenance

Since 2006 Garry Betty Scholar in Adrenocortical Cancer Research

Member of the Endocrine Society and the Deutsche Gesellschaft fuer Endokrinologie

Research Interest

Role of telomere maintenance in adrenocortical carcinogenesis and development

Our laboratory has recently cloned the gene mutation responsible for the adrenocortical dysplasia (acd) mouse. This mouse mutant was first described in 1994 and displays a disorganized adrenal cortex consisting of cytomegalic pleomorphic cells. The gene mutated in these mice, Acd/Tpp1 encodes a part of the telomere cap complex, which is important to protect telomeres, the outer ends of the chromosomes, from recognition by and deleterious activation of the DNA repair machinery. Additionally Act/TPP1 regulates telomerase access to the telomere. Over the course of consecutive cell divisions telomeres usually shorten due to the end replication problem and critically shortened dysfunctional telomeres may lead to the execution of apoptosis or senescence. To overcome telomere shortening human tumors reactivate telomerase or alternative telomere maintenance mechanisms (ALT) in order to ensure unrestricted clonal proliferation.

Specific research focuses are
1) the role of TMMs in human adrenal tumors and
2) the role of dysfunctional telomeres in carcinogenesis:

1) In order to understand TMMs in adrenocortical neoplasms we use tissue samples collected at the University of Michigan (Collaboration with Dr. T.J. Giordano, Dept. of Pathology). Tissue samples, gene expression arrays and tissue arrays are analyzed for several surrogate markers of TMM, such as PNA-FISH/PML immunocytochemistry, TRAP assay and telomere length analysis. This research is aimed to understand TMMs in adrenocortical cancer explore its usefulness in experimental therapy and diagnosis.

2) Using the acd mouse model and MEFs derived from this mouse strain we are currently investigating the role of telomere dysfunction in adrenocortical development and carcinogenesis. Probably most of the acd phenotype can be explained by the telomere dysfunction induced removal of cells from the proliferative pool through senescence and apoptosis. Acd/TPP1 deficient cells develop chromosomal fusions and other genomic abnormalities which could through breakage fusion bridge cycles provide the basis for malignant transformation. Similar genomic aberration are commonly described in human tumors, though the mechanisms through which they occur is not fully understood. Crossing the acd mice to other mouse strains lacking tumor suppressor genes may provide an additional oncogenic event enhancing tumorgenisis. We are currently analyzing some of these double mutant mice.

My overall interest is to add to the understanding of the pathophysiology of the adrenal cortex. Rather than generally studying mechanisms of carcinogenesis or general embryonic development my research is clearly focused on the organ of the adrenal cortex. While common diseases such as colon, breast and prostate cancer are well researched, adrenocortical cancer is an often neglected disease. This may be due to the very low incidence of adrenocortical cancer, affecting 1-2/Million population per year, as well as to the fact that this disease very often falls in between disciplines, mainly oncology and endocrinology. From my perspective, the interdisciplinary approach basic and clinical research makes it a very interesting research area. The ultimate goal is to translate some of the experimental results into clinical medicine, therapy and diagnostic procedure.


Literature

Else, T. and Hammer, G. D., Lingappa, V. R. (2005): Disorders of the Hypothalamus and Pituitary Gland in Pathophysiology of Disease: An Introduction to Clinical Medicine (McGraw-Hill, Eds. McPhee, S.J., Lingappa, V.R. and Ganong, W.F.)
 

Else, T. and Hammer, G. D. (2005): Adrenal Neoplasms Big & Small in Clinical Endocrinology Update (Toronto, Endocrine Society)

Else, T. and Hammer, G. D. (2006): Adrenocortical Function, factors controlling development thereof in Encyclopedia of Stress (Elsevier, Ed. Fink, G.)
 

Keegan, C.E., Hutz, J.E., Else, T., Adamska, M., Shah, S.P., Kent, A.E., Howes, J.M., Beamer, W.G. and Hammer, G.D. (2005): Urogenital and caudal dysgenesis in adrenocortical dysplasia (acd) mice is caused by a splicing mutation in a novel telomeric regulator. Hum Mol Genet 14(1):113-23
 

Else, T. and Hammer, G.D. (2005): Genetic Analysis of Adrenal Abscence: Agenesis and Aplasia. TEMS 16(10): 458-468
Lichtenauer, U., Duchniewicz, M., Kolanczyk, M., Höflich, A., Hahner, S., Else, T., Bicknell, A. B., Tomasz Zemojtel, T., Stallings, N. R.,

Hammer, G. D., Scheele, J., Beuschlein, F. (2007): Pbx-1 and SF-1 synergistically affect adrenocortical growth and steroidogenesis. Endocrinology 148(2):693-704
 

Hockemeyer, D., Palm, W., Else, T., Daniels, J. P., Takai, K. K., Ye, J. Z., Keegan, C. E. , de Lange, T., Hammer, G. D. (2007):Telomere protection by mammalian Pot1 requires interaction with Tpp1. Nat Struct Mol Biol. 14(8):754-61.
 

Else, T., Theisen, B. K., Yipin Wu, Y, Hutz, J. E., Keegan, C. E., Hammer, G. D., Ferguson, D. O. (2007):Tpp1/Acd maintains genomic stability through a complex role in telomere protection Chromosome Research (in press)

Else, T.,Giordano, T. J. ,Hammer, G. D.: Evaluation of Telomere Length Maintenance Mechanisms in Adrenocortical Carcinoma. (in review)