
Lei MaoRobert Koch Institut | RKI · Department for Infectious Disease Epidemiology
Lei Mao
Robert Koch Institute
About
80
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Introduction
Dr. Lei Mao is passionate in continuous research and teaching in a broader field of Life Sciences. She teaches at Charité Berlin and at the Technical University Berlin. Her current research involves bioinformatics, systems biological and research data management at the Robert Koch Institute, Germany.
Additional affiliations
September 2014 - September 2014
November 2014 - present
October 2012 - present
Publications
Publications (80)
Mycobacterium (M.) abscessus infections in Cystic Fibrosis (CF) patients cause a deterioration of lung function. Treatment of these multidrug-resistant pathogens is associated with severe side-effects, while frequently unsuccessful. Insight on M. abscessus genomic evolvement during chronic lung infection would be beneficial for improving treatment...
Mycobacterium (M.) abscessus infections in Cystic Fibrosis (CF) patients cause a deterioration of lung function. Treatment of these multidrug-resistant pathogens is associated with severe side-effects, while frequently unsuccessful. Insight on M. abscessus genomic evolvement during chronic lung infection would be beneficial for improving treatment...
Der ELN-Wegweiser soll sowohl Verantwortlichen für Informationsinfrastrukturen als auch Forschenden die notwendigen Informationen an die Hand geben, den Entscheidungsprozess zur Auswahl eines geeigneten ELN individuell und bedarfsgerecht gestalten zu können.
Mycobacterium avium subsp. hominissuis (MAH) is an opportunistic human pathogen widespread in the environment. Genomic islands (GI)s represent a part of the accessory genome of bacteria and influence virulence, drug-resistance or fitness and trigger bacterial evolution. We previously identified a novel GI in four MAH genomes. Here, we further explo...
As just one species in the larger ecosystem, the health and disease status of human beings is highly dependent on other biological species in their environment, both inside and outside of the human body. Since proteins are the major functional building blocks of the biological world, most homeostasis regulations are realized at the protein level. D...
D inosaurierkochen, ein Gürtel-tier und weiße Pappschachteln liegen auf dem Tischi mA usstel-lungssaal 14 des Berliner Museums für Naturkunde.V orsichtig öffnet Heinrich Mallison einen der Kartons und holt einen präparierten Marder heraus.A nd er Pfote baumelt das kleine Etikett mit der Sammlungs-nummer."Dasi st ZMB_61493", ruft der wissenschaftlic...
This discussion paper is the joint effort of the Dechema Zukunftsforum Biotechnologie. I was heavily involved in the writing of chapter 1: “Gesundheit”, and also co-worked in chapter 2.
This discussion paper is the joint effort of the Dechema Zukunftsforum Biotechnologie. Fourty years after the first study dealing with the potential of biotechnology the Zukunftsforum, as a group of young scientists takes a look at the role of biotechnology to realize the bioeconomy.
The advancement of modern therapy concepts has dramatically extended the postsurvival rates of patients with malignant gastric cancer. However, a remaining setback is the drug resistance of recurrent cancer, which casts a dark shadow over disease prognosis. The original work of Klein et al. [Proteomics Clin. Appl. 2013, 7, 813-824] has outlined a r...
Yeast has been an established model system for cellular aging since more than 50 years and has functioned as a model that allows the investigation of individual gene functions, of gene and protein interactions, and of network structures through individual assays to high-throughput experiments. Thanks to the unbiased screening repertoire yeast will...
Yeast has been an established model system for cellular aging since more than 50 years and has functioned as a model that allows the investigation of individual gene functions, of gene and protein interactions, and of network structures through individual assays to high-throughput experiments. Thanks to the unbiased screening repertoire yeast will...
Hormesis describes the drug action of low dose stimulation and high dose inhibition. The hormesis phenomenon has been observed in a wide range of biological systems. Although known in its descriptive context, the underlying mode-of-action of hormesis is largely unexplored. Recently, the hormesis concept has been receiving increasing attention in th...
Gene expression profiles can be used to infer previously unknown transcriptional regulatory interaction among thousands of genes, via systems biology 'reverse engineering' approaches. We 'reverse engineered' an embryonic stem (ES)-specific transcriptional network from 171 gene expression profiles, measured in ES cells, to identify master regulators...
Genetic background of an individual can drastically influence an organism’s response upon environmental stress and pathological stimulus. Previous studies in inbred rats showed that compared to Brown Norway (BN), Dahl salt-sensitive (SS) rat exerts strong hypoxia susceptibility. However, despite extensive narrow-down approaches via the chromosome s...
Structure of the hypoxia-associated genetic core network de novo generated by information theoretic network remodeling approach using the transcriptomic data. Node 1 and Node 2 are genes (indicated by gene symbol) that significantly co-regulate, and therefore potentially interact. The weight of interaction is given in the third column.
Enriched Gene Ontology terms, KEGG pathways, gene set, and cytogenetic bands of protein expression alterations under different system conditions. The first number gives the number of genes belong to the given enriched term. Number in parenthesis indicates the multiple test adjusted p-value (Fisher’s exact Test).
ABSTRACT: Parkinson's disease (PD) is histologically well defined by its characteristic degeneration of dopaminergic neurons in the substantia nigra pars compacta. Remarkably, divergent PD-related mutations can generate comparable brain region specific pathologies. This indicates that some intrinsic region-specificity respecting differential neuron...
Kainate, a glutamate analogue, activates kainate and AMPA receptors inducing strong synaptic activation. Systemic kainate application to rodents results in seizures, neurodegeneration, and neuronal remodeling in the brain. It is therefore used to investigate molecular mechanisms responsible for these conditions. We analyzed proteome alterations in...
Neurodegenerative disorders (ND) belong to the most devastating diseases in the industrialized western world. Alzheimer disease (AD) is the most prevalent among these disorders followed by Parkinson disease (PD). Huntington disease (HD) is an autosomal dominantly inherited condition with a single mutation that causes disease in almost 100% of all c...
Dosage imbalance is responsible for several genetic diseases, among which Down syndrome is caused by the trisomy of human chromosome 21.
To elucidate the extent to which the dosage imbalance of specific human chromosome 21 genes perturb distinct molecular pathways, we developed the first mouse embryonic stem (ES) cell bank of human chromosome 21 ge...
Identification and validation of inducible/exchangeable recombinant mES clones. (a) Recombinant mES clones were identified by PCR analysis. (b) q-PCR analysis and Luciferase assays using Dual Luciferase Reporter Assay System was performed on mES clones overexpressing the firefly luciferase (Luc) gene. The system was activated upon the removal of Tc...
List of 32 genes overexpressed in mouse ES cells. In this table we list the 32 genes selected to be integrated in the Rosa26 locus and overexpressed using the Tet-off system in mES cells.
Time course of induction of three clones (biological replicates) selected for each gene. In this table we report the time course of the induction of mES clones that overexpress the 32 ORFs. For each gene, three drug-resistant mES biological replicates, whose names are indicated in the specific column, were selected to be tested for their sensitivit...
Summary of q-PCR validation of microarray data. In this table we show the validation by q-PCR of the differential expression of a subset of the most up-regulated and down-regulated genes detected by microarray analysis of the seven effective genes, as ranked by differential expression ratio.
Primer pairs used in q-PCR.
Complete list of differentially expressed genes following the overexpression of Aire, one of the effective genes.
Complete list of differentially expressed genes following the overexpression of Erg, one of the effective genes.
Complete list of differentially expressed genes following the overexpression of Nrip1, one of the effective genes.
Complete list of differentially expressed genes following the overexpression of Pdxk, one of the effective genes.
Comparison of overexpression experiments with the transcriptional response of the transchromosomic tc1 mouse line. X-Y graphs comparing the transcriptional response of Tc1 with the response obtained in the individual overexpression experiments. Each dot represents a gene whose expression was statistically significant in both the Tc1 and the indicat...
A complete list of GO terms significantly enriched in the subsets of genes differentially expressed after overexpression of 11 out of 13 silent genes.
GO enrichment analysis for five (Bach1, Dscr1-Rcan1, DYRK1A, Gabpa and SNF1LK) out of thirteen silent genes, as assessed by microarray analysis. In this table we report the GO enrichment analysis for five out of thirteen silent genes (Bach1, Dscr1-Rcan1, DYRK1A, Gabpa, SNF1LK); supporting references for a subset of significant biological processes...
Complete list of differentially expressed genes following the overexpression of Olig2, one of the effective genes.
Complete list of differentially expressed genes following the overexpression of Runx1, one of the effective genes.
Complete list of differentially expressed genes following the overexpression of Sim2, one of the effective genes.
Raw data of the proteomic analysis, using 2DGE, following the induction of two Runx1 overexpressing clones (E6 and E7). Three technical repeats were performed for each biological replicate: this comprises 6 gels for E6 and 6 gels for E7. For each clone we ran three replicates for t0 (control) and three replicates for t48 hours. Corresponding t0 and...
Comparison of relative expression levels for 20 genes in the EB3 parental cell line and in the inducible clones at 0 hours of induction by multiple statistical t-tests. In this table we show the comparison of the relative expression of 20 genes (the 13 transcription factors, the single transcriptional activator and the 6 kinases) in the EB3 cell li...
A complete list of significantly enriched GO terms for the seven effective genes.
Summary of results derived from the comparison between the analysis of mES overexpressing effective clones and the transchromosomic Tc1 mouse line.
Differential protein expression variation in mES cells overexpressing Runx1. In this table we report the complete list of the proteins whose expression changed following the induction of Runx1
Primer pairs used in PCR.
List of all the mouse orthologs of HSA21 genes sorted according to their basal expression level in mES cells (from the most to the least expressed).
Biological aging is often described by its phenotypic effect on individuals. Still, its causes are more likely found on the molecular level. Biological organisms can be considered as reliability-engineered, robust systems and applying reliability theory to their basic nonaging components, proteins, could provide insight into the aging mechanism. Re...
Progenitor cells such as mesenchymal stem cells (MSCs) have elicited great hopes for therapeutic augmentation of physiological regeneration processes, e.g., for bone fracture healing. However, regeneration potential decreases with age, which raises questions about the efficiency of autologous approaches in elderly patients. To elucidate the mechani...
Huntington's disease (HD) is fatal in humans within 15 to 20 years of symptomatic disease. Although late stage HD has been studied extensively, protein expression changes that occur at the early stages of disease and during disease progression have not been reported. In this study, we used a large 2‐D gel/mass spectrometry based proteomics approach...
We have analyzed three mouse models for Alzheimer's disease (AD) using our high‐resolution 2‐dimensional gel electrophoresis technology in combination with fluorescent dyes and mass spectrometry. We found numerous protein expression changes in brain regions of transgenic mice which largely preceeded the occurrence of amyloid plaques. Interestingly,...
In recent years proteomics became increasingly important to functional genomics. Although a large amount of data is generated by high throughput large-scale techniques, a connection of these mostly heterogeneous data from different analytical platforms and of different experiments is limited. Data mining procedures and algorithms are often insuffic...
Huntington disease (HD) is fatal in humans within 15-20 years of symptomatic disease. Although late stage HD has been studied extensively, protein expression changes that occur at the early stages of disease and during disease progression have not been reported. In this study, we used a large two-dimensional gel/mass spectrometry-based proteomics a...
Cell volume alteration represents an important factor contributing to the pathology of late-onset diseases. Previously, it was reported that protein biosynthesis and degradation are inversely (trans) regulated during cell volume regulation. Upon cell shrinkage, protein biosynthesis was up-regulated and protein degradation down-regulated. Cell swell...
Proteins significantly altered in transgenic mouse brain regions hippocampus (H) and cortex (C) of different ages (1, 2, 7 and 15 months) as well as in cortex of 16 days old APP23 mouse embryos (ED16).
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The amyloid precursor protein (APP) was assumed to be an important neuron-morphoregulatory protein and plays a central role in Alzheimer's disease (AD) pathology. In the study presented here, we analyzed the APP-transgenic mouse model APP23 using 2-dimensional gel electrophoresis technology in combination with DIGE and mass spectrometry. We investi...
In recent years, a large number of proteomics studies for various diseases were conducted, such as for cancer, cardiovascular and neurodegenerative disorders (NDs). The availability of huge data sets with a large number of differentially expressed proteins showed for the first time that not all protein changes between a diseased and a control state...
Treatment of mice by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridene hydrochloride (MPTP) is a well established animal model for Parkinson's disease (PD), while overexpression of L1 cell adhesion molecule (L1cam) has been proposed to attenuate the degeneration of dopaminergic neurons induced by MPTP. To gain insight into the role of L1cam in the patho...
Mouse embryonic brain development involves sequential differentiation of multipotent progenitors into neurons and glia cells. Using microarrays and large 2-DE, we investigated the mouse brain transcriptome and proteome of embryonic days 9.5, 11.5, and 13.5. During this developmental period, neural progenitor cells shift from proliferation to neuron...
Cardiovascular diseases are known to manifest different clinical symptoms in men and women. Basically this is due to gender-specific genotypes and sexual hormones. We studied gender specificity on the protein expression level in the mouse and human heart, with particular emphasis on the age-dependency of sex-specific protein expression. We first st...
Protein expression profile changes in transgenic ES cell lines.
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Supplementary method of network entropy calculation
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Large numbers of protein expression changes are usually observed in mouse models for neurodegenerative diseases, even when only a single gene was mutated in each case. To study the effect of gene dose alterations on the cellular proteome, we carried out a proteomic investigation on murine embryonic stem cells that either overexpressed individual ge...
Brains of the mouse from three developmental stages, embryo day 16 (Ed16), postnatal stage one week (1W) and eight weeks (8W), were distributed to different laboratories for a collaborative proteome analysis (The Human Brain Proteome Project). As one of the laboratories involved in this project, we separated total protein extracts of the brains by...
Neurodegenerative disorders (ND) encompass clinically and genetically heterogeneous diseases with considerable overlap of their clinical, neuropathological and molecular phenotype. Various causes of neurodegeneration in disease may affect eventually the same proteins within protein networks. To identify common changes in ND, we compared brain prote...
The accumulation of mitochondria containing mutated genomes was proposed to be an important factor involved in aging. Although the level of mutated mtDNA has shown to increase over time, it is currently not possible to directly measure the mtDNA mutation rate within living cells. The combination of mathematical modeling and controlled experiments i...
Neurodegenerative disorders (ND) are often age-associated, chronic and progressive diseases without effective long-term treatment modalities. The identification of proteins at common nodal points in the regulatory network of ND may add to our understanding of their (common) pathology and provide a foothold for therapy. In an effort to characterize...
In vitro culture models that employ human liver cells could be potent tools for predictive studies on drug toxicity and metabolism in the pharmaceutical industry. A bioreactor culture model was developed that permits the three-dimensional co-culture of liver cells under continuous medium perfusion with decentralised mass exchange and integral oxyge...
An important consideration for the utilisation of in vitro culture models for studies on drug metabolism as an alternative to animal testing is the maintenance of a defined degree of cell differentiation. Thus, in vitro conditions reflecting as near as possible the in vivo situation of the cells within the whole organ are required. A bioreactor was...
Eine besondere Schwierigkeit bei der Etablierung von in vitro-Modellen mit Humanzellen liegt derzeit in der unzureichenden Verfügbarkeit von humanem Lebergewebe. Die wachsende Zahl von split-liver-Transplantationen könnte zwar in Zukunft dazu beitragen, daß Lebergewebe gesunder Spender zugänglich ist, jedoch kann die Konservierung von Spenderorgane...
Aufgrund der zentralen Rolle der Leber in der Verstoffwechselung von Fremdstoffen sind in vitro-Leberzellkulturmodelle zum Ersatz von Metabolismusstudien am Tier von besonderem Interesse. Der Fortschritt im Bereich der Gentechnik in den letzten Jahren hat die Etablierung humaner Leberzellinien ermöglicht. Gegenüber primären Leberzellen bieten Zelli...
An important consideration for the standardization of in vitro culture models for studies on xenobiotic metabolism as an alternative to animal experiments is the maintenance of a defined degree of cell differentiation. A hepatocyte bioreactor was developed which allows the reorganization of hepatocytes and nonparenchymal cells of the liver to form...
Alternativ zu Tierversuchen läßt sich der hepatische Metabolismus pharmakologisch wirksamer Substanzen in Leberzellkulturen in vitro untersuchen; sichere und reproduzierbare Modelle, die außerdem günstige Voraussetzungen zur Reduktion der Entdifferenzierung der Hepatozyten aufweisen, sind jedoch dafür erforderlich.
Die Alterungsforschung hat heute aufgrund der Verschiebung der demografischen Altersstruktur eine hohe Bedeutung. Ziel der Habilitationsschrift war es, Einblicke in die allgemeinen Mechanismen des Alterns zu erhalten. Inspiriert durch den Bereich des System-Engineering wurde die Reliabilitätsstheorie als eine vielversprechende Theoriebasis gewählt....