Anastasia obtained her B.Sc. (Hons) degree in Pharmacology from the University of Sunderland with a Sandwich year (in respiratory pharmacology) at Bayer PLC in 1998. Her PhD in cell biology and cell physiology took place at the University of East Anglia (2002) in the laboratory of Jelena Gavrilovic, and investigated the role of hepatocyte growth factor and cell-matrix interactions in alveolar epithelial wound healing.

Anastasia’s research career has been focussed in the biomedical area. Her postdoctoral positions (2002-2009) were undertaken in the Department of Respiratory Medicine at the University of Cambridge in the laboratories of Edwin Chilvers and Nicholas Morrell, where she investigated the role of granulocytes in lung inflammation and asthma, and receptor trafficking in pulmonary arterial hypertension.

In 2009 she worked at the Institute of Food Research, Norwich where she set up an intravital bio-imaging facility and started new research within the field of gut mucosal immunology.  Here she aimed to understand how gut epithelial stem cells are regulated by the innate immune system during homeostasis and inflammatory bowel disease. 

In October 2016 Anastasia joined the School of Pharmacy at the University of East Anglia as a Lecturer in Pharmacology. Her work has continued on  gut mucosal immunbology and she has returned to lung research investigating mechanisms of resistance in non small cell lung cancer.

The long-standing research interest of the Sobolewski lab is the study of mucosal tissue, in particular that of the lung and the gut during health, inflammation and cancer.   Experimentally we use an integrated approach: Our research traverses epithelial stem cells, the innate immune system and cell-to-cell communication, alongside 3-D organoid and tumouroid experimental models and bio-imaging.

LUNG EPITHELIAL RESEARCH IN CANCER: Non-small cell lung cancer is a disease with a poor prognosis due to its detection at a late stage. Patients become resistant to treatments and understanding how this occurs is important for identifying new therapeutic targets. In 2012, a new mechanism of chemoresistance tunnelling nanotubes (TNTs) was discovered. TNTs are long, thin cytoplasmic extensions that can extend between cells over long distances (up to 400µm). TNTs are able to transport intracellular signalling molecules and organelles such as mitochondria and so affect the function of each other conferring chemoresistance. Although stress, low nutrients and hypoxia, all of which are present in the tumour microenvironment, have been shown to induce TNTs, now much is known about specific endogenous factors also present in the tumour microenvironment may regulate TNT formation.

Our research on non-small cell lung cancer using lung adenocarinoma cells has identified that hepatocyte growth factor, which is upregulated in these patients can induce tunnelling nanotubes (Awanis et al. 2023). We have identified that crosstalk between the HGF receptor c-met and the β-1 integrin promotes TNT formation. Understanding the specific cell signalling pathways in TNT formation will help identify new therapeutic targets for the treatment of non-small cell lung cancer.  Our ongoing research concentrates on the role of hepatocyte growth factor receptor cross talk with other growth factor receptors and different integrin subtypes.  

GUT EPITHELIAL RESEARCH: Our gut research involved discovering how the gut epithelial barrier is regulated. The gut epithelial barrier, is required to stop the external environment  in the gut lumen, that includes food and microbiota from making contact with our underlying mucosal immune system, so preventing an immune response. This barrier is key for homeostasis and is compromised in in inflammatory bowel disease. Renewal of the epithelium takes place by the division of crypt epithelial stem cells, their differentiation into different epithelial cell types and the renewal of the epithelium. How different cytokines and immune cells regulate the gut epithelium is   not fully understood.

Our research has shown that innate immune cells such as monocytes and macrophages can regulate epithelial renewal and crypt stem cells differently in health versus inflammation (Skoczek et al. 2014, Raveenthiraraj et al. 2023).. Our work published in the Journal of Immunology has demonstrated a previously unidentified role for autocrine IL-6 signaling in the maintenance of the small intestinal crypt stem cell niche, through the differential expression of the IL-6 receptor and downstream STAT3 signaling in Paneth cells and the Wnt signaling pathway (Jeffery  et al. 2018. Our ongoing work is also focussed on understanding how epithelial-derived (autocrine) or immune cell-derived (paracrine) affect gut epithelial renewal.

Using gut organotypic culture we have shown that in health the intact crypt epithelial barrier first detects any changes in bacterial composition of the gut lumen and then rapidly recruits underlying Ly6C+ monocytes (via the MyD88 signalling pathway) from the smooth muscle and submucosal layers to the crypt epithelial stem cell niche. This physical repositioning of monocytes is significant because it causes temporary alterations in the rate renewal of the epithelium thus allowing fine tuning of immune responses to maintain health and barrier function.  We have also shown that monocytes help maintain the number of crypt epithelial stem cells in vivo; further supporting our hypothesis that immune-epithelial interactions are important in the maintenance of tissue homeostasis.

Homeostasis is a tightly regulated process requiring finely-tuned complex interactions between different cell types, growth factors / cytokines and their receptors.  Another hypothesis in my lab is that the signaling pathways of these factors also play a role in stem cell driven tissue renewal during homeostasis or inflammation and that these factors may be epithelial-derived (autocrine) or immune cell-derived (paracrine).

PAST GROUP MEMBERS
Dagmara Skczoek (PhD student)
Petr Walcyzsko (Postdoc); Andy Goldson (Postdoc); Vicki Jeffery (PhD student); Sathuwarman Raveenthiraraj (PhD student); Griselda Awanis (PhD student); Amy Judge (MSc student); Ritty Jose (MSc student); Frances Perret (MSc Student); Imogen Clarke (MSc student); The Dung Nguyen (Msc student); Aya Elmeligy (MSc student)

CURRENT GROUP MEMBERS
Salonee Banerjee (PhD student); Natalila Cicovacki (MRes student); Rhys Constable (MSc student); Katharine Williams (MSc student); Rushikesh Rajendra (MSc student)

CURRENT ADMINSTRATIVE POSTS:

Director of Employability

Module Organiser on Gastrointestinal Diseases and Cancer PHA5010B

Year 2 Lead Pharmacology and Drug Discovery BSc 

PREVIOUS ADMINSTRATIVE POSTS:
Webpage Coordinator; Member of Web Steering Group Committee 

Pharmacy Research Day Coordinator