Prof Julia Cordero - Local and Systemic Functions of the Intestine in Health and Disease
Introduction
The adult intestine is a major barrier epithelium with vital endocrine, immune and metabolic roles, leading to the coordination of whole-body physiology. These functions are achieved by specialised cells such as absorptive enterocytes and secretory enteroendocrine cells, which are generated by intestinal stem cells (ISCs). Stem cells constantly repair the intestinal epithelium by adjusting their proliferation and differentiation to tissue intrinsic as well as micro- and macro-environmental signals. How do these signals integrate to preserve intestinal and whole-body health?
Work in our laboratory is devoted to deciphering the cellular and molecular mechanisms regulating ISC behaviour during tissue regeneration and tumourigenesis. We are also interested in understanding how the intestine interacts with other tissues and organs to maintain organismal balance and how these interactions are deregulated in intestinal diseases such as cancer or inflammation. We use the fruit fly Drosophila melanogaster as our primary in vivo research model system combined with suitable mammalian paradigms.
Our research aims to identify mechanisms that could be used in translational efforts to restore intestinal regeneration as well as to prevent malignant transformation of the intestine and alleviate the systemic consequences of intestinal malfunction.
Biography
Education and qualifications
2007. Ph.D. degree in the Molecular Cell Biology Program, Washington University School of Medicine. Saint Louis, MO, USA. Thesis Advisor: Dr. Ross L. Cagan
1999: “Licenciada en Biología Molecular”, San Luis National University. San Luis, Argentina.
Appointments
2016-present: Senior Research Fellow, School of Cancer Sciences, University of Glasgow.
2016-present: Honorary Group Leader, Cancer Research UK Scotland Institute, Glasgow.
2016-Present: Senior Research Fellow. Wolfson Wohl Cancer Research Centre. Institute of Cancer Sciences, University of Glasgow.
2014-2016. Junior Research Fellow. Wolfson Wohl Cancer Research Centre. Institute of
Cancer Sciences. University of Glasgow. Glasgow, United Kingdom.
2009-2014: Postdoctoral Fellow, Cancer Research UK Beatson Institute
2007-2008: Post-doctoral Fellow, Mount Sinai School of Medicine New York, NY. USA
2000-2002: Research Assistant, Department of Internal Medicine, Renal Division, Washington University School of Medicine, Saint Louis, MO, USA
Recent Publications
2024
Medina AB, Perochon J, Johnson C, Tian Y, Bellec K, Yu Y, Cordero JB. Neuroendocrine Control of Intestinal Regeneration Through the Vascular Niche in Drosophila. bioRxiv. 2024:2024.2009.2010.612352.
2022
Chen Z, Cordero J, Alqarni AM, Slack C, Zeidler MP, Bellantuono I. Zoledronate Extends Health Span and Survival via the Mevalonate Pathway in a FOXO-dependent Manner. J Gerontol A Biol Sci Med Sci. 2022;77:1494-1502.
Medina A, Bellec K, Polcowñuk S, Cordero JB. Investigating local and systemic intestinal signalling in health and disease with Drosophila. Dis Model Mech. 2022; 15:dmm049332
2021
Guillermin O, Angelis N, Sidor CM, Ridgway R, Baulies A, Kucharska A, Antas P, Rose MR, Cordero J, Sansom O, Li VSW, Thompson BJ. Wnt and Src signals converge on YAP-TEAD to drive intestinal regeneration. Embo j. 2021:e105770.
Hodgson JA, Parvy JP, Yu Y, Vidal M, Cordero JB. Drosophila Larval Models of Invasive Tumorigenesis for In Vivo Studies on Tumour/Peripheral Host Tissue Interactions during Cancer Cachexia. Int J Mol Sci. 2021;22: 8317
Nászai M, Bellec K, Yu Y, Román-Fernández A, Sandilands E, Johansson J, Campbell AD, Norman JC, Sansom OJ, Bryant DM, Cordero JB. RAL GTPases mediate EGFR-driven intestinal stem cell proliferation and tumourigenesis. Elife. 2021 Jun 7;10:e63807.
Perochon J, Yu Y, Aughey GN, Medina AB, Southall TD, Cordero JB. Dynamic adult tracheal plasticity drives stem cell adaptation to changes in intestinal homeostasis in Drosophila. Nat Cell Biol. 2021; 23:485–496
2020
Bellec K, Cordero JB. The Peroxisome: A New Player in Intestinal Epithelial Repair. Dev Cell. 2020;53:131-132.
2019
Johansson J, Naszai M, Hodder M, Pickering K, Miller BW, Ridgway RA, Yu Y, Peschard P, Brachmann B, Campbell AD, Cordero, JB1, Sansom, OJ. RAL GTPases drive intestinal stem cell function and regeneration through internalization of WNT signalosomes. Cell Stem Cell. Apr 4;24(4):592-607.e7. Commentary in Cell Stem Cell 2019 Apr 4;24:499-500.
Parvy JP1, Yu Y, Dostalova A, Kondo S, Kurjan A, Bulet P, Lemaitre B, Vidal M, Cordero JB. The antimicrobial peptide Defensin cooperates with Tumour Necrosis Factor to drive tumour cell death in Drosophila. Elife. 2019;8: e45061. Recommended by the Faculty of 1000.
Scopelliti A, Bauer C, Yu Y, Zhang T, Krüspig B, Murphy DJ, Vidal M, Maddocks OK, Cordero JB. A neuronal relay mediates a nutrient responsive gut/fat body axis regulating energy homeostasis in adult Drosophila. Cell Metab. 2019 Feb 5;29:269-284.e10.
2018
Parvy JP, Hodgson JA, Cordero JB. Drosophila as a Model System to Study Nonautonomous Mechanisms Affecting Tumour Growth and Cell Death. Biomed Res Int. 2018:7152962.
Perochon J, Carroll LR, Cordero JB. Wnt Signalling in Intestinal Stem Cells: Lessons from Mice and Flies. Genes (Basel). 2018;9. pii: E138.
2017
Tian A, Benchabane H, Wang Z, Zimmerman C, Xin N, Perochon J, Kalna G, Sansom OJ, Cheng C, Cordero JB, Ahmed Y. Intestinal stem cell overproliferation resulting from inactivation of the APC tumor suppressor requires the transcription cofactors Earthbound and Erect wing. PLoS Genet. 2017 Jul 14;13:e1006870.
2016
Scopelliti A, Bauer C, Cordero J and Vidal M. Bursicon-α subunit modulates dLGR2 activity in the adult Drosophila melanogaster midgut independently to Bursicon-β. Cell Cycle. 2016;15:1538-44.
Elbediwy A, Vincent-Mistiaen ZI, Spencer-Dene B, Stone RK, Boeing S, Wculek SK, Cordero J, Tan EH, Ridgway R, Brunton VG, Sahai E, Gerhardt H, Behrens A, Malanchi I, Sansom OJ, Thompson BJ. Integrin signalling regulates YAP and TAZ to control skin homeostasis. Development. 2016;143:1674-87.
Lab Members
Group Leader
Julia Cordero
Julia.Cordero@glasgow.ac.uk
Julia Cordero was born and raised in Argentina. After completing her University studies in her home country, Julia moved to the USA to her PhD studies in the laboratory of Ross Cagan at Washington University in St Louis where she studied developmental tissue patterning in Drosophila. In 2009, Julia moved to Owen Sansom’s group at the CRUK Beatson Institute in Glasgow for her postdoctoral work, funded by Marie-Curie and EMBO long-term fellowships. During her post-doc Julia discovered novel mechanisms driving intestinal regeneration and cancer using both flies and mice. Julia started her independent research group towards the end of 2014 at the Institute of Cancer Sciences, University of Glasgow, funded by a Dorothy Hodgkin Fellowship from the Royal Society, a Sir Henry Dale Fellowship from the Wellcome Trust and Royal Society and, most recently, a Wellcome Trust Senior Research Fellowship. Julia is Professor of Systemic Signaling Biology at the University of Glasgow and Honorary Group Leader at the CRUK Beatson Institute. Julia’s laboratory combines Drosophila and mouse model systems to study local and whole-body functions of the intestine in health and disease. Outside of the lab, Julia enjoys travelling, physical exercise and, most of all, spending time with her family.
Postdoctoral Scientists
Karen Bellec
Karen.Bellec@glasgow.ac.uk
Karen was born and raised in France. After studies in Cellular Biology and Genetics, she joined the Epithelia Dynamics and Mechanics’ team for her PhD under the supervision of Dr Roland Le Borgne in Rennes, France. Karen’s PhD work focused on the role of the Stratum protein in the regulation of Notch signalling in Drosophila melanogaster. This project allowed her to develop great skills in genetics, advanced microscopy and intracellular trafficking. Karen joined the lab in January 2019 to study how intestinal stem cells adapt to tissue damage to drive regeneration and to also tip the balance in favour of French Nationals in the lab.
Jack Holcombe
Jack.Holcombe@glasgow.ac.uk
Jack studied Biology at the University of Sheffield followed by a brief foray into Amphioxus evo-devo for his Masters at St Andrews. During his time in St Andrews Jack became fascinated by our bodies ability to withstand damage and maintain a homeostatic environment. Realising he would need a new experimental workhorse; Jack entered the wonderful world of Drosophila. For his PhD Jack moved to the Weavers lab at the University of Bristol where he explored the metabolic mechanisms that drive tissue resilience and healthy renal function. Alongside this, he also investigated the modes of cellular and subcellular repair that support effective wound closure. Drawn back to Scotland by the mountains and the promise of some exciting science, Jack joined the lab in February 2024 to explore inter-organ signaling in the maintenance of gut homeostasis. Outside of the lab he is most likely to be found halfway up a cliff or stood under a boulder of some form.
Jessica Perochon
Jessica.Perochon@glasgow.ac.uk
Always passionate about Life science, Jess followed her undergraduate education in her natal Paris with a PhD at the University of Versailles Saint Quentin-en-Yvelines (UVSQ), also in France. During her PhD, she worked with Drosophila as a model organism to study the consequences of chronic Endoplasmic Reticulum (ER) stress at the molecular and tissue level. After her PhD, Jess realised she loved flies and whisky too much and then decided to move to Scotland for a post-doc in our lab at the end of 2015. Jessica’s project involves inter-organ communication programs and their impact on intestinal homeostasis. More precisely, she studies the communication between intestinal stem cells and the gut associated, vasculature-like tracheal system.
Parvathy Ramesh
Parvathy.Ramesh.2@glasgow.ac.uk
Parvathy was born and raised in India. After completing her Masters in Life Sciences, she joined Developmental Genetics Lab at Indian Institute of Science Education and Research, Mohali, India to purse her PhD under the supervision of Prof. Lolitika Mandal. Parvathy’s PhD work focused on understanding the role played by NF-kB signalling in Developmental hemopoiesis using Drosophila larval hematopoietic organ ‘lymph gland’ as the model system. This project allowed her to enhance her skills in genetics, microscopy and infection biology. Parvathy joined the lab in March 2023 and is currently trying to understand the immune control of local and systemic manifestations of Colorectal Cancer (CRC) in Drosophila as well as the crosstalk’s between gut and brain in CRC like conditions. Apart from science, Parvathy loves to go for weekend hikes and is passionate about photography.
Lab Manager/Principal Scientific Officer
Yachuan Yu
Y.Yu@crukscotlandinstitute.ac.uk
Yachuan was born in China where he trained as a Chemist. After that, he moved to the UK, to do a PhD and postdoc at the University of Swansea, studying genome stability and DNA repair with Prof. Raymond Waters. He then did a second postdoc on spermatogenesis in Drosophila under the direction of Prof. Helen White-Cooper. In 2013, Yachuan joined Marcos Vidal’s group at the CRUK Beatson Institute as a Scientific Officer/Lab manager and, since 2016, he has become a central member of our laboratory. He is not only responsible for the everyday management of the lab and overall technical assistance but also for the development and troubleshooting of new techniques. Yachuan’s contribution over the years has been essential to allow Julia to create a friendly and competitive research environment as well as to keep her sanity (to a certain extent…).
PhD Students
Utkarsh Bhore
2951428b@student.gla.ac.uk
Hailing from India, Utkarsh's lifelong curiosity centres around how signals mould organisms' choices and adaptations. His research journey kicked off with an internship investigating the interplay of dispersal, nutritional availability, and environmental cues on survival strategies. 🧬Diving deeper into this field, he realised that environmental signals control whole-body homeostasis through various signalling pathway. His master's thesis at IISER Berhampur focused on the role of miRNA let-7 in ovarian development, using Drosophila as a model. His research extended to exploring miRNA let-7's role in Wilms tumour using cell lines, guided by mentors Dr. R Selvi Bharathavikru and Dr. Bodhisatta Nandy.🔬Utkarsh is grateful to have received a studentship from Cancer Research UK, allowing him to delve into the intricacies of the gut-brain axis and its disruptions in intestinal cancer. He hopes that his dedication and passion will contribute to the collective knowledge of how environmental and systemic cues influence organismal adaptations. Between research endeavours, he eagerly looks forward to exploring the Scottish Highlands, inspired by the magic of Harry Potter and the adventures of Doctor Who. 🏞️📚🚀
Cai Johnson
2818374j@student.gla.ac.uk
Born in North Wales, Cai grew up in a small village on the side of the Mawddach estuary. He moved to Lancaster in 2019 to complete a BSc in Biochemistry with Genetics, where he completed a dissertation project investigating DNA replication initiation and kinase inhibition in various cancer types. Following obtaining his undergraduate degree, he studied for an MSc in Cancer Research and Precision Oncology at the University of Glasgow, where he completed a project exploring the anti-cancer properties of γδ T-Cells in colorectal cancer. Captivated by colorectal cancer research with a keen interest in intestinal stem cell regulation, Cai joins the Lab in October 2023 for his PhD in collaboration with Professor Massimo Vassalli and Dr. Andrei Shvarts at the School of Engineering. During his PhD, Cai he will take a multidisciplinary approach, integrating biophysical, computational mechanics and genetic experiments to investigate intestinal/microenvironment interactions during intestinal regeneration and cancer. Cai enjoys doing anything sports-related in his spare time, especially football and running.
Jade Phillips
2715765p@student.gla.ac.uk
Jade did her BSc and MRes at Imperial College London where she studied the impact of respiratory infections on lung cancer progression in the lab of Dr Cecilia Johansson. It is during this time that Jade became interested in tumour-microenvironment interactions and decided this was something she wanted to study further. She started PhD in the Cordero lab in October 2021 after being awarded a studentship from CRUK to study inter-organ communication between the intestine and its associated vasculature in health and disease. Jade is interested in understanding how the mechanics of the intestinal epithelium change during damage or tumorigenesis and how this affects angiogenesis.
Yuanliangzi Tian
2575026t@student.gla.ac.uk
Tian was born and raised in China. She did her undergraduate studies in Animal Science at Sichuan Agricultural University, where she studied the intestinal bacteria adaptation to the bamboo diet of the Giant Panda. This lab experience inspired her interests in biological research and drove her to do a Master’s degree. Since then, she started to work on Drosophila with a main focus on the function of vacuolar ATPases in the maintenance of adult intestinal homeostasis. Beyond that, she also did some work on the screening of anti-ageing agents using Drosophila as a model system. In 2020, Tian got her Master’s degree in Genetics and was awarded a scholarship from the China Scholarship Council to join our lab as a PhD student. Because of the pandemic, Tian arrived in the lab in March 2021, which was six-month later than expected. However, she is now here, and we are all very excited to have her with us to continue her research with amazing fly intestine and the metabolic adaptations it undergoes during regeneration.
Lab Celebration photos