Prof. Mandrup heads the Mandrup Laboratory which is among the world leading laboratories in the field of transcriptional networks that regulate adipocyte differentiation and function. Her group was among the first to apply deep sequencing-based technologies to investigate aspects of transcriptional networks (Nielsen et al., 2008), and since then they have investigated various aspects of transcription factor networks in many different cell systems including adipocytes, mesenchymal stem cells, and pancreatic β-cells, and have integrated this with metabolic data.
The Mandrup Laboratory was also the first to map chromatin remodeling during a differentiation process (Siersbæk et al 2011), and using a combined genomics and proteomics approach they demonstrated extensive cooperativity between transcription factors at the level of genomics hotspots and super-enhancers at early stages of adipogenesis (Siersbæk et al, 2014).
Moreover they showed that browning of human adipocytes involves considerable genomic reprogramming involving PPARγ super-enhancers, and they identified KLF11 as a transcription factor that is required for this process (Loft et al., 2015). They showed that activation of inflammatory pathways in adipocytes drives a selective co-factorsquelching from super-enhancers that mediates the repression of the adipocyte gene program (Schmidt et al. 2015).
They used promoter capture HiC to generate the first dynamic 3D map of how enhancers contact their promoters during a differentiation process (Siersbæk et al., 2017). Recently, the group showed that commitment of mesenchymal stem cells to adipocytes and osteoblasts follows different strategies for activation of enhancers, and they applied IMAGE, a novel machine-learning algorithm developed in-house (Madsen et al. 2018), to predict the relative contribution of all expressed transcription factors. This allowed them to identify a large group of stem cell factors that act as molecular switches of this process (Rauch et al, 2019).
M. Madan Babu
Prof. Babu heads the Center for Data Driven Discovery at the Section for Structural Biology, St. Jude Childrens' Research Hospital (2020- ) and is an Adjunct Professor at SDU, Odense (2017-).
His group investigates how regulation is achieved at multiple levels of complexity in cellular systems and how this influences evolution of organisms and their genome. His group has established new computational approaches to analyse, integrate and interpret biological systems of different scales (atomic-, molecular-, omic- cellular- and population-scale) and develops algorithms for biological data mining and data integration. More recently, his group developed (a) experimental approaches to discover functions of protein segments and their variants, and (b) machine-learning approaches to understand how natural variation can influence protein function.
This expertise in diverse areas of genomics, population genetics, computational and systems biology is critical for data analysis, identification of obesity associated genes, gene networks, signaling signatures of adipocytes and understanding the impact of natural variation within ADIPOSIGN. Recently, Madan’s group established the molecular signatures of GPCRs, which are the targets for over one-third of approved drug targets. By integrating this knowledge with human polymorphisms, his group revealed the molecular origins of variability in drug response, with implications for personalized and precision medicine.
Equally significant is their research on unstructured proteins, which do not adopt defined structures but still perform critical function for survival. Their paradigm-shifting work firmly established the previously under-appreciated roles of unstructured proteins in biology and disease.
Prof. Kornfeld was recently recruited as Professor to Department for Biochemistry and Molecular Biology, University of Southern Denmark (2018), where he is now heading a research group focusing on the role of noncoding RNAs and epigenomics modifiers in the control of adipocyte function.
He is particularly interested in the role of these modifiers during nutritional overload, extended lifespan and calorie restriction. JWK has a strong background in mouse (patho)-physiology, transgenesis, noncoding RNAs, and (post)-transcriptional gene regulation, which will greatly benefit ADIPOSIGN in functionally interrogating the altered molecular circuitry of adipocytes during metabolic disease.
Assoc. Prof. Gerhart-Hines heads the Brown Adipose Metabolism group at the Novo Nordisk Foundation (NNF) Center for Basic Metabolic Research at the University of Copenhagen.
His group seeks to understand the molecular underpinnings of environmental and circadian control in adipose biology and systemic energy homeostasis. His group is particularly focused on identifying the G protein-coupled receptor (GPCR) signaling networks mediating this control. ZGH employs a wide array of adipose-related genetic mouse tools and state-of-the-art in vivo metabolic phenotyping instrumentation.
This expertise and technology will be of immense value in driving the physiological characterizations in ADIPOSIGN. As a demonstration of early success from his efforts studying adipose GPCRs, ZGH has recently formed a spin-out company, Embark Biotech IvS, based on an adipocyte-derived GPCR ligand to treat obesity.