Valerio Orlando

  Professor, Bioscience · Head Environmental Epigenetics Research Program

  Office Location: Ibn Al Haytham (Building 2) · Level 3 · Room 3234
  KEEP Website:
                                             Faculty lab website:​

Research Keywords
Chromatin; Epigenetics; Cell Identity; Adaptation; Reprogramming

Research Interests
After the completion of human genome sequencing, it became clear that most of its information (90%) does not satisfies the dogma: one gene-one protein; rather most of it is noncoding, yet essential for life.

Indeed, the DNA‐centered dogma for genetic information is now evolving into a much more complex and flexible dimension provided by the discovery of the Epigenome. This comprises specific structural and topological chromosome components that by complementing DNA-based information determine genome functional organization and expression of cell specific genetic programs. In global terms, the epigenome constitutes the chromosomal molecular interface that allows the genome to interact with the environment. In this context, the epigenome enables cells to learn, remember and maintain their functional states throughout life and enable organisms to integrate environmental signals.

Thus, exploration of how the genome interacts with the environment via the epigenome is now key to fully understand mechanisms of cell and complex organism adaptation and plasticity and how this impacts fundamental aspects of life including development, ageing, nutrition, behavior and associated diseases.

Prof. Orlando's lab is interested in investigating the chromatin and nuclear architecture mediated mechanisms that control cell identity and plasticity. These include signaling to chromatin and nuclear organization by Polycomb proteins; the role of ncRNA and nuclear RNA interference (RNAi) in epigenetic regulation, Epigenomics and how this relates for development and adaptation (e.g. Metabolism), in particular in stress conditions.

Furthermore, as part of the investigation of the mechanistic plastic properties of the genome in response to developmental and environmental cues, Prof. Orlando's lab focuses also on the epigenetic regulation of the expression and dynamics of mammalian transposable elements and their role in cell differentiation, reprogramming and disease.

Main Techniques
Chromatin Immunoprecipitation, Chromosome Conformation Capture, Genome Structural Variation (SNP, CNV, Indels) Transcriptomics, ncRNA analysis, TAP-TAG purification, Proteomics, Generation of stable cell lines, Primary cell culture and induced pluripotent stem cells (iPSC).

Members of the Lab

Dr. Muhammad Shuaib, Research Scientist

Personal profile:

- 2012–2014: Postdoctoral Fellow at the Institute of Genetics Molecular and Cellular Biology (IGBMC), Strasbourg, France. Main subject; the role of CENP-A modifications in faithful chromosome segregation.

- 2008-2012 PhD in Molecular and Cellular Biology, University of Strasbourg and IGBMC, France. Supervisor: Dr. Ali Hamiche, thesis topic: Epigenetic mechanisms of CENP-A loading to centromeric chromatin.

- 2007–2008: Lecturer, Department of Biotechnology, in the University of Malakand, Pakistan.

- 2002-2006 B.S. (Hons) in Biotechnology (Gold medalist). Department of Biotechnology, University of Malakand, Pakistan

Research interests: 

The genome of eukaryotic cell is packed in the form of chromatin, which is comprised of DNA, histone and non-histone proteins. Epigenetic regulations such as chemical modification of DNA or histones and changes in chromatin structure affect how cellular machineries read the genomic information. Muhammad has broad interests in various epigenetic regulatory systems such as Polycomb group proteins (PcG), noncoding RNAs (ncRNA), nuclear RNAi, histone marks and DNA methylation. He obtained Ph.D., from the University of Strasbourg, where he studied the role of histone variant (CENP-A) in epigenetic specification of centromeres and kinetochore formation. He continued his postdoctoral work at the IGBMC, where he studied the role of CENP-A modifications (Phosphorylation / ubiquitination) in cell division and chromosome segregation. 

Currently in KAUST, he is focusing on different projects like; 

- To understand how Polycomb group proteins (PcG) are recruited to specific target genes and regulate their transcription, particularly during cellular differentiation or in response to environmental changes

- To understand the role of ncRNAs in epigenetic regulation and find out how they interact with chromatin-modifying complexes (e.g PcG)

- To explore the link between gene regulation and proteins that write, read and erase histone marks in normal development versus stress condition

- To uncover the function of chromatin associated RNAi machinery in muscle cells

- To focus on developing new techniques to investigate locus specific protein complexes and RNA-protein interaction

Selected publications: 

Shuaib M, Goutte-Gattat D, Ouararhni K, Dimitrov S, Hamiche A. (2014). “Identification of a novel kinase, which is required for CENP-A phosphorylation and faithful chromosome segreggation.” (Submitted to Nature)

Goutte-Gattat* D, Shuaib M*, Ouararhni K*, Gautier T, Skoufias D.A, Hamiche A, Dimitrov S.  “Phosphorylation of the CENP-A amino-terminus in mitotic centromeric chromatin is required for kinetochore function.” Proc Natl Acad Sci USA (2013) 110 (21): 8579-8584. (* Equal contribution) 

Hamiche A, Shuaib M.  “Chaperoning the histone H3 family.” Biochim Biophys Acta-Gene Regulatory Mechanisms (2012) 1819 (3-4): 230-237.

Shuaib M, Ouararhni K, Dimitrov S, Hamiche A.  “HJURP binds CENP-A via a highly conserved N-terminal domain and mediates its deposition at centromeres.” Proc Natl Acad Sci USA (2010) 107(4): 1349-1354. 

Drané P, Ouararhni K, Depaux A, Shuaib M, Hamiche A.  “The death-associated protein DAXX is a novel histone chaperone involved in the replication-independent deposition of H3.3.” Genes & Development (2010) 24(12): 1253-1265.          

Fellowships and awards:

- Post-doctoral Fellowship, French National Institute of Health and Medical Research (INSERM). (2012-2014).                                                                  

- Doctoral Fellowship, French Association for Cancer Research (ARC). (2010-2012)

- PhD Scholarship, Higher Education Commission of Pakistan, for PhD study. (2008-2010)

- Ph.D award 2012, University of Strasbourg, France. (2012). 

- Gold Medal award, Department of Biotechnology, University of Malakand, Pakistan. (2006)

- Travel grant, by University of Strasbourg for 6th Meeting of the Doctorals Schools, Charles University, Prague, Czech Republic. (2010)

- Travel grant, by “European Medicine Research Training Network” and AstraZeneca. EMTRAIN PhD Workshop 2012, AstraZenecca, Manchester, UK.

Dr. Majula Thimma, Research Scientist

Personal profile: 

- 2006 M.Sc (Bioinformatics), University of London.

- 1992 B.Tech (Electronics & Communication Engineering), Anna University, India.

- 1989 B.Sc., (Physics), Madurai Kamaraj University, India.

Research interests: 

Manjula is interested in working on the bioinformatics analysis of the genomic and transcriptomic data generated by the high throughput sequencing platforms.  Various experimental model systems are used to study the functional landscape of epigenetic variations at genome levels and their impact on regulation of gene expression. Manjula is involved in developing bioinformatics analysis pipeline and also by using various bioinformatics software’s that are available to analyze the data in close conjunction with the team members. 

Selected publications: 

Mojib N, Amad M, Thimma M, Aldanondo N, Kumaran M, Irigoien X. “Carotenoid metabolic profiling and transcriptome-genome mining reveal functional equivalence among blue-pigmented copepods and appendicularia.” Mol Ecol. (2014) PMID: 24803335

Hunter S, Apweiler R, Attwood TK, Bairoch A, Bateman A, Binns D, Bork P, Das U, Daugherty L, Duquenne L, Finn RD, Gough J, Haft D, Hulo N, Kahn D, Kelly E, Laugraud A, Letunic I, Lonsdale D, Lopez R, Madera M, Maslen J, McAnulla C, McDowall J, Mistry J, Mitchell A, Mulder N, Natale D, Orengo C, Quinn AF, Selengut JD, Sigrist CJ, Thimma M, Thomas PD, Valentin F, Wilson D, Wu CH, Yeats C.InterPro: “the integrative protein signature database.” Nucleic Acids Res (2009) 37 (Database issue): D211-5. doi: 10.1093/nar/gkn785. Epub 2008 Oct 21.PMID

Tomlinson C, Thimma M, Alexandrakis S, Castillo T, Dennis JL, Brooks A, Bradley T, Turnbull C, Blaveri E, Barton G, Chiba N, Maratou K, Soutter P, Aitman T, Game L, “MiMiR--an integrated platform for microarray data sharing, mining and analysis.” BMC Bioinformatics (2008) 18; 9:379. doi: 10.1186/1471-2105-9-379.PMID:18801157

Mueller M, Goel A, Thimma M, Dickens NJ, Aitman TJ, Mangion J. “eQTL Explorer: integrated mining of combined genetic linkage and expression experiments.” Bioinformatics (2006)15;22(4):509-11. Epub 2005 Dec 15. PMID:16357031

Dr. Gregorio Alanis-Lobato, Postdoc

Personal profile:

- 2009-2010 MSc Computer Science following the Artificial Intelligence/Bioscience track, Department of Mathematical and Computer Sciences and Engineering, King Abdullah University of Science and Technology (KAUST), Saudi Arabia

- 2005-2009 BSc Computer Systems Engineering, Department of Computer Systems, ESCOM - National Polytechnic Institute (NPI), Mexico

- 2002-2005 Technician in Software Programming, Department of Programming, CECyT 9 “Juan de Dios Bátiz Paredes” - NPI, Mexico

Research interests: 

Gregorio’s research interests focus on the identification of genes, proteins and the interactions between them that play important roles in the onset and development of complex human diseases (e.g. Duchene Muscle Dystrophy). For this purpose, he employs and develops machine learning, network science and systems biology techniques for the analysis of massive amounts of biological data.

Selected publications: 

Alanis-Lobato, G., Cannistraci, C.V. & Ravasi, T. “Exploring the Genetics Underlying Autoimmune Diseases with Network Analysis and Link Prediction. “, Proceedings of the MECBME 2014, 167-170.

Alanis-Lobato, G., Cannistraci, C.V. & Ravasi, T. “Exploitation of genetic interaction network topology for the prediction of epistatic behavior.” Genomics (2013) 102(4), 202-208.

Cannistraci, C.V., Alanis-Lobato, G. & Ravasi, T. “Minimum curvilinearity to enhance topological prediction of protein interactions by network embedding.” Bioinformatics 29, i199-i209.

Yanal Ghosheh, PhD student

Personal profile: 

- 2009-2011 MSc Department of Mathematical and Computer Sciences and Engineering, King Abdullah University of Science and Technology (KAUST), Saudi Arabia

- 2004-2009 BSc Computer Engineering, Department of Computer Engineering, Jordan University, Jordan

Research interests:

Yanal is in his third year of PhD study, he is interested in transcriptomic analysis of the non-coding RNA, in particular lncRNA and piRNA and their roles in differentiation and disease in human as well as in mouse development.

Nadine El said, PhD student

Personal profile: 

- 2010-2013 Teaching assistant at the Pharmacognosy/Phytochemistry department at Ain Shams University

- 2009-2011 M.Sc in biotechnology, American University of Cairo –AUC- Cairo, Egypt

- 2003-2008: B.Sc. in Pharmaceutical Sciences, Ain Shams University, Cairo, Egypt

She obtained her MSc in Biotechnology from the American University in Cairo (AUC) with a thesis on identifying Subtilisin Serine protease from the Atlantis II Brine pool of the Red Sea using both metagenomic functional and computational screening approaches (having a KAUST fellowship at AUC for funding my research as part of a collaboration between KAUST and AUC), and B.Sc. in Pharmacy and pharmaceutical Sciences from Ain Shams University.

Research interests:

Nadine is interested in studying the role of chemical modification of ncRNA and Polycomb complex in regulating mammalian skeletal muscle cell function.

Philip Walter, PhD student

Personal profile: 

- 2011- 2012 M.Sc. Chemistry, King Abdullah University of Science and Technology (KAUST).

- 2011 B.Sc. Chemistry, La Sapienza, University of Rome, Italy.

Research interests:

Philip is interested in epigenetics, chromatin, ncRNA, transposons, and  cell differentiation. Philip is investigating the role of chromatin associated SINE/ALU and LINE noncoding RNA in the context of terminal differentiation and stress response in skeletal muscle cells.

Selected publication: 

Daniele M. Scarpino Schietroma, Mattia R. Monaco, Valerio Bucalossi, Philipp E. Walter, Patrizia Gentili and Marco Bella. The Rabe amination after a century: direct addition of N-heterocycles to carbonyl compounds. Org. Biomol. Chem (2012) 10, 4692.

Saba Nathif, PhD student

Personal profile: 

- 2012- 2014 M.Sc in Bioscience, King Abdullah University of Science and Technology (KAUST), Thuwal, KSA

- 2007- 2010 B.Sc in Biotechnology, Taif University, Taif, KSA

Research interests:

Saba is interested in working with Polycomb group proteins (PcG) and trying to investigate the connection between basic epigenetic pathways that include Polycomb complexes, DNA methylation and histone marks and their role in normal development and diseases such as cancer.

Bodor Fallatah, PhD student

Personal profile: 

- 2012- 2013 M.Sc in Bioscience, King Abdullah University of Science and Technology (KAUST), Thuwal, KSA

- 2007- 2010 B.Sc Biological science, department of Biochemistry, King Abdul-Aziz University, Jeddah, KSA

Research interests:

RNA interference (RNAi) is an important pathway that regulates gene expression in several organisms. The role of RNAi in post-transcriptional gene silencing in the cytoplasm is well characterized. However, the association of RNAi components with chromatin and their role in transcriptional regulation is not clear. I am interested in investigating the role of RNAi in the nucleus and how this can impact gene transcription during cell differentiation, adaptation or under stress conditions.

Anastasia Kefalea, Laboratory Manager

Personal profile: 

- 2007-2010: Specialist Diploma in Clinical Immunology, Awarded by the Institute of Biomedical Science, UK

- 2004-2005: Postgraduate Certificate in Biomedical Science, University of Westminster, UK

- 1994-1998: BSc (Hons) Biochemistry with Medical Biosciences, University of Kent, UK

Research interests:

Anastasia is from Greece and spent twelve years in the UK obtaining her academic qualifications and subsequently working for the NHS as a specialist Biomedical Scientist in Immunology. She has received her BSc in Biochemistry with Medical Biosciences from the University of Kent and her PGC in Biomedical Science from the University of Westminster. Her competence to practice as a Biomedical Scientist was awarded by the Health Professions Council (HPC) in the UK in 2005 and she received her Specialist Diploma in Clinical Immunology by the Institute of Biomedical Science (IBMS) in 2010.

Sabir Adroub, Research Technician

Personal profile: 

- 2008-2010 M.Sc. in Biotechnology, RMIT University of Melbourne, Australia

- 2003-2006 B.Sc. in Biotechnology, Adelaide University, Australia

Research interests: 

Next Generation Sequencing, qPCR for copy number and gene expression, SNPs Microarray for genotyping and copy number analysis, Chromosomes analysis and fish.

Selected publications: 

D Ganesamoorthy, DL Bruno, G McGillivray, F Norris, SM White, S Adroub, DJ Amor, A Yeung, R Oertel, MD Pertile, C Ngo, AR Arvaj, S Walker,d,e P Charan, R Palma- Dias, N Woodrow, HR Slater. Meeting the challenge of interpreting high resolution SNP-array data in prenatal diagnosis: Does increased diagnostic power outweigh the risk of uncertain variants? . British Journal of Obstetrics and Gynaecology (2013) 120(5):594-606. doi: 10.1111/1471-0528.12150. 

Yung S Ho, Sabir A Adroub, Maram Abadi, Bader Al Alwan, Reham Alkhateeb, Ge Gao, Alaa Ragab, Shahjahan Ali, Dick van Soolingen, Wilbert Bitter, Arnab Pain, Abdallah M Abdallah. Complete genome sequence of Mycobacterium vaccae type strain ATCC 25954. J Bacteriol. (2012) 194(22): 6339-40. doi: 10.1128/JB.01462-12.

Yung S Ho, Sabir A Adroub, Fajr Aleisa, Hanan Mahmood, Ghofran Othoum, Fahad Rashid, Manal Zaher, Shahjahan Ali, Wilbert Bitter, Arnab Pain, Abdallah M Abdallah. Complete genome sequence of Mycobacterium fortuitum subsp. Fortuitum type strain DSM46621.  J Bacteriol. (2012) 194(22):6337-8. doi: 10.1128/JB.01461-12