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.

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  • 171 studies published from Nov. 1, 2020 to Oct. 1, 2021
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Adelheid (Heidi) Lempradl, Ph.D.

Assistant Professor, Department of Metabolism and Nutritional Programming

Areas of Expertise

Epigenetics, metabolism, intergenerational inheritance, nutritional programming

Biography

Dr. Adelheid (Heidi) Lempradl is an assistant professor in Van Andel Institute’s Metabolic and Nutritional Programming group, where she investigates how the parental metabolic state is transmitted through generations. She earned her diploma and her Ph.D. from University of Vienna, where she used fluorescent probes to study the structure and folding of lipid membranes and RNAs. She continued her RNA work as a postdoctoral fellow in the lab of Dr. Leonie Ringrose at University of Austria, followed by a fellowship in the lab of Dr. Asifa Akhtar at Max Planck Institute of Immunology and Epigenetics in Freiburg, Germany. Most recently, she was a fellow in the lab of Dr. J. Andrew Pospisilik, also at Max Planck. Her research was the first to demonstrate that acute paternal diet of Drosophila can reprogram offspring metabolism. This work also identified the first epigenetic signature of obesity that is conserved across species, which established the value of Drosophila as a model for intergenerational inheritance. She was the recipient of the 2002 DOC-fFORTE Ph.D. Fellowship from the Austrian Academy of Sciences, was nominated for the Helmholtz Young Investigator Diabetes (HelDi) Award in 2018, and has given invited talks at numerous meetings and symposia, including the keynote address at the SETAC/iEOS Joint Topic Meeting on Environmental and (Eco) Toxicological Omics and Epigenetics.

Selected Publications

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 subtypesNat Metab.

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

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

Justice AE…Lempradl A…Lindgren CM. 2019. Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distributionNat 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 diabetesCell 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 obesityNat 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 homeostasisCell 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 obesityCell 164(3):353–364.

Lempradl A, Penninger JM, Pospisilik JA. 2015. Exploring the emerging complexity in transcriptional regulation of energy homeostasisNat 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 obesityCell 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 elementNat Genet 46(9):973–981.
*Co-first authors

Teperino R, Lempradl A, Pospisilik JA. 2013. Bridging epigenomics and complex disease: the basicsCell 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 methodsChembiochem 8(10):1137–1145.

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

Luba Ginzburg

Research Associate

Ellen Griggs, B.S.

Van Andel Institute Graduate School Student

Thesis: The combined effect of maternal obesity and autism spectrum disorder-associated genetic mutations on neurodevelopment

Dmitri Martirosov

Laboratory Aide

Michelle Minard, B.S.

Senior Administrative Assistant II

Eduardo Perez-Mojica, Ph.D.

Postdoctoral Fellow

Mechanistic dissection of epigenetic inheritance

Joe Roy, BLS, B.S.

Assistant Research Technician

April Rickle

Van Andel Institute Graduate School Student

Thesis: Impact of toxins and nutrients on brain function and development

2022;Krittika Sudhakar;061422;Krittika;Sudhakar;SELECTED

Krittika Sudhakar, Ph.D.

Postdoctoral Fellow

Thesis: The effect of maternal nutrition on offspring development and metabolism