People of Beyond the exome
Prof. Dr. med. Heiko Krude
Institut für Experimentelle Pädiatrische Endokrinologie
Augustenburger Platz 1,
D-13353 Berlin, Germany
Phone: +49 (0)30 4505 566292
FAX: +49 (0)30 4505 66916
Heiko Krude, MD, is a tenured full professor for Experimental Pediatric Endocrinology at the Charité University Hospital, Berlin and director of the Institute for Experimental Pediatric Endocrinology (IEPE). The IEPE harbors the Pediatric Outpatient clinic where clinical studies can be conducted. It also provides lab space for the experimental work as well as for the Berlin Neonatal Screening Program for inherited diseases. In addition he is co-director of the Berlin Center for Rare Diseases (BCSE). He received his doctorate at the Free University of Berlin in 1995 and worked as fellow in pediatrics and later specialized in “pediatric endocrinology” at the “Kaiserin Auguste Viktoria Children’s Hospital” as well as the Charité Children’s Hospital. He finished his training with the Board Certificate in Pediatrics in 2003 and Board certificate in “Pediatric Endocrinology” in 2009. Based on his thesis in molecular endocrinology and his research training as post-doc in the thyroid development-lab of Roberto DiLauro in Naples, Italy, he was always dedicated to the close gap between clinical endocrine questions and their molecular basis, which made him fascinated by translational pediatric endocrinology. His particular research fields were from the beginning on inherited defects with a focus on genetic alterations of the endocrine regulation of body weight and defects in thyroid gland development and thyroid function. Based on an early publication describing a new obesity-syndrome in 1998 (POMC deficiency, Krude et al. 1998) a 15 year ongoing research effort eventually resulted in the successful treatment of this particular form of genetic obesity by applying the missing neuropeptide MSH in 2016 (Kühnen et al. 2016). Concerning the second main research topic “thyroid”, the molecular cause of the most frequent inherited genetic defect of the endocrine system, congenital hypothyroidism, was in the focus for almost 20 years. The clinical aspects of treatment of congenital hypothyroidism were always his parallel task in the sense of translational medicine (Grüters & Krude 2001). Several genetic new very rare diseases associated with a developmental defect of the thyroid have been discovered (Thorwarth et al. 2014, Krude et al. 2002). However, still the majority of patients with congenital hypothyroidism are left without a molecular diagnosis despite the use of Next Generation Sequencing technologies. Further efforts were undertaken to establish also the search for epigenetic alterations (Kühnen et al. 2016) that might also represent one possible molecular mechanism in the pathogenesis of congenital hypothyroidism. More recently, he is now concentrating in the context of the research program “Beyond the Exome” on likely non-coding genetic variants in the regulatory genome in these particular “unsolved” patients with congenital hypothyroidism.
Kühnen P, Clément K, Wiegand S, Blankenstein O, Gottesdiener K, Martini LL, Mai K, Blume-Peytavi U, Grüters A, Krude H. Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist. N Engl J Med 2016;375:240-6.
Kühnen P, Handke D, Waterland RA, Hennig BJ, Silver M, Fulford AJ, Dominguez-Salas P, Moore SE, Prentice AM, Spranger J, Hinney A, Hebebrand J, Heppner FL, Walzer L, Grötzinger C, Gromoll J, Wiegand S, Grüters A, Krude H. Interindividual Variation in DNA Methylation at a Putative POMC Metastable Epiallele Is Associated with Obesity. Cell Metab 2016;24:502-9.
Thorwarth A, Schnittert-Hübener S, Schrumpf P, Müller I, Jyrch S, Dame C, Biebermann H, Kleinau G, Katchanov J, Schuelke M, Ebert G, Steininger A, Bönnemann C, Brockmann K, Christen HJ, Crock P, deZegher F, Griese M, Hewitt J, Ivarsson S, Hübner C, Kapelari K, Plecko B, Rating D, Stoeva I, Ropers HH, Grüters A, Ullmann R, Krude H. Compre-hensive genotyping and clinical characterisation reveal 27 novel NKX2-1 mutations and expand the phenotypic spec-trum. J Med Genet 2014;51:375-87.
Grüters A, Krude H. Detection and treatment of congenital hypothyroidism. Nat Rev Endocrinol 2011;8:104-13.
Krude H, Schütz B, Biebermann H, von Moers A, Schnabel D, Neitzel H, Tönnies H, Weise D, Lafferty A, Schwarz S, DeFelice M, von Deimling A, van Landeghem F, DiLauro R, Grüters A. Choreoathetosis, hypothyroidism, and pulmonary alterations due to human NKX2-1 haploinsufficiency. J Clin Invest 2002;109:475-80.
Krude H, Biebermann H, Luck W, Horn R, Brabant G, Grüters A. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet 1998;19:155-7.