Portrait of Dr Fani Papagiannouli

Dr Fani Papagiannouli

Lecturer in Biological Sciences / Stem Cell and Developmental Biology

About

Dr Fani Papagiannouli completed her undergraduate studies in Biology (University of Patras, Greece) in 1998 with honors by the State Scholarships Foundation IKY. She started her Ph.D. at the University of Heidelberg (Germany) and the German Cancer Research Center (DKFZ, Heidelberg), working on the role of the highly conserved polarity and tumor suppressor genes dlg, scrib and lgl in the Drosophila male gonads and testis architecture. After completing her PhD in 2003, she continued her research analysing the development and morphogenetic events of the early Drosophila embryo at Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH). In 2009 she joined the Centre for Organismal Studies (COS, Heidelberg) to study the role of the Hox transcription factors abdA and AbdB in the Drosophila testis. Her work uncovered that abdA controls fate transition within the somatic lineage, while AbdB emerged as a key regulator of stem cell niche positioning and architecture. Genome-wide studies revealed that AbdB in pre-meiotic germ cells provides positional cues for integrin localization by directly controlling Boss/Sev signaling between adjacent cell types. In 2016 Fani moved to Stanford University (USA), with an awarded Fellowship from the German Research Foundation (DFG), to study soma-germline communication and signaling regulation in the Drosophila testis, together with Prof. Margaret Fuller. She returned to Germany in 2018 to continue her studies on the mechanisms and factors that regulate germ cell control during spermatogenesis in Drosophila, hosted by Prof. Maria Leptin at the Institute of Genetics in Cologne. Her latest work revealed that cortical polarity and cellular trafficking regulate EGFR in the somatic epithelial-type cyst cells that encapsulate the germ cells and promote germ cell survival and animal fertility. 

Dr Fani Papagiannouli joined the Medway School of Pharmacy in September 2019 as a Lecturer in Biological Sciences with speciality in Stem Cell and Developmental Biology. Her scientific focus is on the mechanisms and factors that regulate stem cell maintenance and how stem cells interact with their neighbouring cells to shape the niche and local tissue microenvironment. Elucidating the role of transcription factors such as the Hox gene AbdB, as well as that of the cortical polarity proteins Dlg, Scrib and Lgl, and nucleoporins in soma-germline coordination, within the complex gene network underlying testis homeostasis, are some of her main research interests.

Specialist areas
Stem Cell & Developmental Biology, Cell Biology, Gene Regulation, Cell Signaling, Spermatogenesis, Drosophila Genetics, Advanced Microscopy, Histology, Genomics, Proteomics, Image Analysis. 

Orchid URL: https://orcid.org/0000-0003-4094-6688 

Research interests

A fundamental question in biology is how cell-cell communication and exchange of short-range signals regulates cell proliferation and cell fate for setting up functional tissues. In all adult tissues harboring stem cells, tissue homeostasis and repair relies on the proper communication of stem cells and of their differentiating daughter cells with the local tissue microenvironment. 

Research in Papagiannouli’s lab aims to understand the principles underlying cell-cell communication and stem cell-related processes in the Drosophila testis. In this system, germline stem cells and their daughter germ cells proliferate and progressively differentiate enclosed in squamous epithelial-type somatic cyst cells, forming a small organoid-like “cyst”, the unit of differentiation. We are particularly interested in how communication between the germline and the somatic cyst cells is established and maintained, in particular how the somatic cyst cells support the developmental decision of the germline during spermatogenesis. The microenvironment of those cysts provides an ideal model system to investigate how key cellular mechanisms such as endocytosis, polarity cues and nucleocytoplasmic transport cooperate with signaling and transcriptional control to maintain cyst cell-germline communication and achieve a coordinated cellular output.

The lab focuses on how cortical polarity components regulate signaling in the male germline system. Fani Papagiannouli has shown that Dlg, Scrib and Lgl are critically required in the somatic lineage to encapsulate the germ cells and preserve the architecture and homeostasis of the male gonads and larval testes (Marhold§, Papagiannouli§ et al., 2003; Papagiannouli, 2013; Papagiannouli and Mechler, 2009, 2010). Latest findings identified Dlg, Scrib, Lgl and clathrin-mediated endocytosis (CME) as key regulators of EGFR signaling, since knockdown of their function leads to increased EGFR signaling levels, apoptotic death of the neighbouring germ cells and infertility of the male flies (Papagiannouli et. al., 2019). Lowering the EGFR signaling levels in cyst cells can rescue the observed defects, restore germ cell survival and the function of the testis-barrier, while the membrane phospholipid PtdIns(4,5)P2 (PIP2) contributes to EGFR/Ras-mediated activation of the MAPK dpERK downstream of the pathway. Future work aims to dissect the precise mechanistic features underlying the Dlg- and CME- mediated regulation of EGFR signaling, by employing highly innovative proteomic approaches and advanced electron microscopy. 
This project is funded by a Medway School of Pharmacy Post Graduate Research Scholarship. 

Other aspects of on-going research in the lab are to decipher the landscape of nucleoporin function in nucleocytoplasmic transport and cyst cell-germline coordination (Papagiannouli et. al., bioRxiv Oct. 24; doi: 10.1101/452466) and build up on the previously identified role of the Hox transcription factor AbdB in stem cell niche positioning and architecture (Papagiannouli et. al., 2014; Schardt et. al., 2015; Papagiannouli et. al., 2015). 

The high degree of conservation of the components we study, at gene and cellular level across species, will allow us to drive qualitative conclusions on how stem cells communicate with their neighbours to replenish differentiated tissues. Given the role of squamous epithelial cells in the development of prevalent human cancers, the outcome of our research will eventually formulate general rules underlying the function of squamous epithelial cells of broader importance. The regulatory strategies uncovered in our studies could collectively aid the identification of new approaches in regenerative medicine and infertility.

Funding attracted:

Soma-Germline communication and coordination in Drosophila spermatogenesis: understanding the role of cortical polarity proteins Dlg, Lgl and Scrib in testis homeostasis
German Research Foundation (Bonn) 
2016-01-01 to 2017-12-31|Grant
GRANT_NUMBER: 290468141
URL: https://app.dimensions.ai/details/grant/grant.5051365
Source: Fani Papagiannouli via ÜberWizard 

Selected Publications:

PubMed URL: https://www.ncbi.nlm.nih.gov/pubmed/?term=Papagiannouli+F

F. PAPAGIANNOULI*, C. W. Berry, M. T. Fuller (2019), The Dlg-module and clathrin-mediated endocytosis regulate EGFR signaling and cyst cell-germline coordination in the Drosophila testis, Stem Cell Reports, May 14, 12: 1-17 (doi.org/10.1016/j.stemcr.2019.03.008)

F. PAPAGIANNOULI*, M. T. Fuller, I. Lohmann (2018), Nuclear export in somatic cyst cells controls cyst cell-germline coordination and germline differentiation in the Drosophila testis, bioRxiv Oct. 24 (doi: 10.1101/452466)

S. Tamirisa§, F. PAPAGIANNOULI§, E. Rempel, O. Ermakova, N. Trost, J. Zhou, J. Mundorf, S. Brunel, N. Ruhland, M. Boutros, J.U.Lohmann, I.Lohmann, (2018), Decoding the Regulatory Logic of the Drosophila Male Stem Cell System, Cell Reports 24, 3072–3086

L. Schardt, J-J Ander, I. Lohmann*, F. PAPAGIANNOULI*, (2015), Stage-specific control of niche positioning and integrity in the Drosophila testis, Mechanisms of Development Nov;138 Pt 3:336-48.

F. PAPAGIANNOULI *, I Lohmann* (2015), Stage-specific control of niche architecture in the Drosophila testis by the posterior Hox gene Abd-B, Computational & Structural Biotechnology J. (CSBJ)  13:122-30. doi: 10.1016/j.csbj.2015.01.001

F. PAPAGIANNOULI*, L. Schardt, J. Grajcarek, N. Ha, I. Lohmann* (2014), The Hox gene Abd-B controls stem cell niche function in the Drosophila testis, Developmental Cell 28(2):189-202

F. PAPAGIANNOULI * (2013), The internal structure of embryonic gonads and testis development in Drosophila melanogaster requires scrib, lgl and dlg activity in the soma, Int.J.Dev.Biol. 57: 25 - 34 (doi: 10.1387/ijdb.120087fp)

F. PAPAGIANNOULI*, I Lohmann* (2012), Shaping the niche: lessons from the Drosophila testis and other model systems, Biotechnol J. 7(6): 723-36

F. Papagiannouli *, B.M. Mechler (2010), discs large in the Drosophila testis, An Old player on a new task, Fly 4(4): 294-8 

F. PAPAGIANNOULI, B.M. Mechler (2009), discs large regulates somatic cyst cell survival and expansion in Drosophila testis, Cell Research 19(10): 1139-49

J. Marhold§, F. PAPAGIANNOULI§, M. Li, A. Patel, B.M. Mechler (2003), Requirements for scribble expression in newly formed gonads of Drosophila embryos, Mechanisms of Development, Gene Expression patterns 3(2): 143-6.

§ Shared first authorship
* Corresponding author

Teaching

Fani Papagiannouli is actively involved in teaching Pharmacy Students (MPharm) on fundamental biological, cellular and physiological mechanisms. The spectrum of learning topics range from cell division (mitosis and meiosis), genetics, patterns of inheritance and disease, epithelia and cancer, reproductive system, cell biological aspects of toxicology and histology of the gastro-intestinal track to basic statistics and aspects of scientific communication. She is a tutor in Foundation and 1st year Pharmacy Undergraduate Students. 

Teaching Modules:
BIOL1057 – Essentials in Biological Sciences
PHAR1033 – Basic Laboratory Skills
PHAR1034 – Endocrine and Gastrointestinal Pharmacology
PHAR1037 – Introduction to Toxicology
PHAR1058 – Drugs and Diseases

Supervision

The lab of Fani Papagiannouli has currently an open position for a PhD student. 

For more details visit the following link [https://www.kent.ac.uk/scholarships/search/FN24SGCIDS01]. 

The Scholarship is available to both UK and EU nationals to apply via the University of Kent website: https://www.msp.ac.uk/postgraduate/?course_id=785&course_level=postgraduate

Self-funded applicants and those who have access to international scholarship applications, please contact directly Dr. Papagiannouli (f.papagiannouli-227@kent.ac.uk). 

Professional

Collaborations:

Prof. Alice Ting, Stanford University School of Medicine 
Dr. Irina Kolotuev, University of Lausanne 

Peer Review Activities:

Stem Cell Reports (Elsevier)
Molecular and Cellular Endocrinology (MCE) (Elsevier)
Cell & Tissue Research (Springer)
Protoplasma (Springer) 
Journal of Visualized Experiments (JoVE)
National Centre for the Replacement Refinement & Reduction of Animals in Research (NC3Rs), UK

Academic Societies:

BSCB (British Society for Cell Biology)
BSDB (British Society for Developmental Biology)
GfE (Gesellschaft für Entwicklungsbiologie/Gemany Society for Developmental Biology)
vBIO (Verband Biologie, Biowissenschaften und Biomedizin/ Association of Biology, Life Sciences and Biomedicine)

Academic Committees at MSoP:

Students Well-being Working Group
Outreach Research Group 

Publications