Lempradl
Laboratory

Intergenerational Inheritance of Nutritional States

How does parental diet impact the health of future offspring? This is one of the many questions the laboratory of Dr. Adelheid (Heidi) Lempradl seeks to answer. With mounting evidence that nutrition and metabolism can have a ripple effect through the generations, it is critically important to gain a better understanding of how these processes work in order to develop interventions that improve human health.

By determining the molecular mechanisms that underlie phenotype transmission across generations, the Lempradl Laboratory aims to identify and systematically map the nutritional and chemical sources of adverse intergenerational effects. Their ultimate goal is to develop novel ways to prevent transmission of harmful phenotypes to subsequent generations and thus, in the long term, improving health.

Dr. Lempradl and her colleagues were the first to show that paternal diet reprograms metabolism of the offspring in Drosophila. Their findings also identified one of the first gene networks required for proper intergenerational metabolic programming. Additionally, they identified the first epigenetic signature associated with obesity that is conserved across species, firmly establishing Drosophila as a valuable model in the field of intergenerational inheritance.

Her earlier work also resulted in major advances in the understanding of how DNA regulatory elements control gene expression. In 2014, she and her colleagues published novel evidence that strand-specific RNA transcripts act as a key developmental switch for regulatory elements, representing a simple and elegant system for enabling highly complex temporal and spatial gene regulation in development.

Dror E, Fagnocchi L, Wegert V, Apostle S, Grimaldi B, Gruber T, Panzeri I, Heyne S, Höffler KD, Kreiner V, Ching R, Lu TTH, Semwal A, Johnson B, Senapati P, Lempradl A, Schones D, Imhof A, Shen H, Pospisilik JA. 2023. Epigenetic dosage identifies two major and functionally distinct β cell subtypes. Cell Metab.

Pérez-Mojica JE, Enders L, Walsh J, Lau KH, Lempradl A. 2023. Continuous transcriptome analysis reveals novel patterns of early gene expression in Drosophila embryos. Cell Genom.

Yang CH, Longinotto J, Panzeri I, Arrigoni L, Wegert V, Heyne S, Seifert G, Lempradl A, Bonisch U, Pospisilik JA. 2022. Isolation and processing of murine white adipocytes for transcriptome and epigenome analyses. J Vis Exp 184:e64128.

Yang CH*, Fagnocchi L*, Apostle S, Wegert V, Casani-Galdón S, Landgraf K, Panzeri I, Dror E, Heyne S, Wörpel T, Chandler DP, Lu D, Yang T, Gibbons E, Guerreiro R, Brás J, Thomasen M, Grunnert LG, Vaag AA, Gillberg L, Grundberg, E, Conesa A, Körner A, PERMUTE, Pospisilik JA. 2022. Independent phenotypic plasticity axes define distinct obesity subtypes. Nat Metab.

*Co-first authorship
**Highlighted in News & Views
***Dr. Lempradl is part of PERMUTE

Lempradl A. 2019. Germ cell-mediated mechanisms of epigenetic inheritance. Semin Cell Dev Biol.

Justice AE…Lempradl A…Lindgren CM. 2019. Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution. Nat Genet 51(3):452-469.

Lu TT, Heyne S, Dror E, Casas E, Leonhardt L, Boenke T, Yang CH, Sagar, Arrigoni L, Dalgaard K, Terperino R, Enders L, Selveraj M, Ruf M, Raja SJ, Xie H, Boenisch U, Orkin Sh, Lynn FC, Hoffman BG, Grün D, Vovouri T, Lempradl A, Pospisilik JA. 2018. The Polycomb-dependent epigenome controls b cell dysfunction, dedifferentiation and diabetes. Cell Metab 27(6):1294–1308.

Turcot V, Lu Y, Highland HM, Schurmann C, Justice AE, Fine RS, Bradfield JP, Esko T, Giri A, Graff M, Hendricks AE, Karaderi T, Lempradl A, …, Pospisilik JA, Rivadeneira F, Borecki IB, Deloukas P, Frayling TM, Lettre G, North KE, Lindgren CM, JN Hirschhorn, Loos RJF. 2018. Protein-altering variants associated with body mass index implicate 1 pathways that control energy intake and expenditure underpinning obesity. Nat Gen 50(1):26–41.

Theurich S, Tsaousidou E, Hanssen R, Lempradl A, Mauer J, Timper K, Schilbach K, Folz-Donahue K, Heilinger C, Sexl V, Pospisilik JA, Wunderlich FT, Brüning JC. 2017. IL-6/Stat3-dependent induction of a distinct, obesity-associated NK cell subpopulation deteriorates energy and glucose homeostasis. Cell Metab 26(1):171–184.

Dalgaard K, Landgraf K, Heyne S, Lempradl A, Longinotto J, Gossens K, Ruf M, Orthofer M, Strogantsev R, Selvaraj M, Casas E, Teperino R, Surani MA, Zvetkova I, Rimmington D, Tung L, Larder R, Yeo GSH, O’Rahilly S, Whitelaw E, Penninger JM, Jenuwein T, Cheung CL, Ferguson-Smith AC, Coll AP, Körner A, Pospisilik JA. 2016. Trim28 haploinsufficiency triggers bi-stable epigenetic obesity. Cell 164(3):353–364.

Lempradl A, Penninger JM, Pospisilik JA. 2015. Exploring the emerging complexity in transcriptional regulation of energy homeostasis. Nat Rev Genet 16(11):665–681.

Ost A*, Lempradl A*, Casas E, Weigert M, Tiko T, Deniz M, Pantano L, Boenisch U,Itskov PM, Stoeckius M, Ruf M, Rajewsky N, Reuter G, Iovino N, Ribeiro C, Alenius M, Heyne S, Vavouri T, Pospisilik JA. 2014. Paternal diet defines offspring chromatin state and intergenerational obesity. Cell 159(6):1352–1364.
*Co-first authors

Herzog VA*, Lempradl A*, Trupke J, Okulski H, Altmutter C, Ruge F, Boidol B, Kubicek S, Schmauss G, Aumayr K, Ruf M, Pospisilik A, Dimond A, Senergin HB, Vargas ML, Simon JA, Ringrose L. 2014. A strand-specific switch in noncoding transcription switches the function of a Polycomb/Trithorax response element. Nat Genet 46(9):973–981.
*Co-first authors

Teperino R, Lempradl A, Pospisilik JA. 2013. Bridging epigenomics and complex disease: the basics. Cell Mol Life Sci 70(9):1609–1621.

Lempradl A, Ringrose L. 2008. How does noncoding transcription regulate Hox genes? Bioessays 30(2):110–121.

Stampfl S, Lempradl A, Koehler G, Schroeder R. 2007. Monovalent ion dependence of neomycin B binding to an RNA aptamer characterized by spectroscopic methods. Chembiochem 8(10):1137–1145.

Lempradl A, Stampfl S, Koehler G. 2004. RNA-antibiotics interactions: A spectroscopic study of conformational changes upon binding. 48^th Annual Meeting of the Biophysical Society, Baltimore Biophysical Journal 86(1):143A–143A part 2.