Dr Rasha Abu Eid

Biography

I qualified as a dentist in 2001 (University of Jordan). During my years of study, I developed a keen interest in Oral Pathology, and in particular in the pathology of malignant and premalignant oral lesions. I therefore joined a postgraduate research program in Oral Pathology at the University of Birmingham, England. The focus of my research was the quantification of oral cancer and pre-cancer growth patterns using digital imaging. I successfully completed my PhD in 2005, and worked as a Research fellow in the same institute.

In 2006, I joined the academic staff at the Faculty of Dentistry at the University of Jordan as an Assistant Professor in Oral Pathology.

In 2009 I joined the Academic staff of the newly established Dental School at the University of Aberdeen. 

During my time in Aberdeen, I studied for my PGCert in Higher Education Teaching and Learning, and I completed the course in July 2011 and became a fellow of the Higher Education Academy.  

In 2011, I was successful in securing a prestigious research fellowship from the King Hussein Institute for Biotechnology and Cancer to conduct state of the art research in the field of cancer immunology in USA. My fellowship was split between the National Cancer Institute/ National Institutes of Health and Georgia Regents University (Currently Augusta University), where I later became an Assistant Research Scientist. The focus of our research group was T cell Biology and the modulation of the immune system as part of cancer immune therapy.

In October 2016, I re-joined the Academic staff at the University of Aberdeen Dental School as a Senior Lecturer in Oral Sciences. My primary research focus is T cell biology, head and neck cancer immunology in addition to applications of digital pathology.

Research Overview

My main research interests are in digital pathology and cancer immunology and immunotherapy in different cancer types.

I have a special focus on various aspects of head and neck cancer. This includes the objective diagnosis and quantification of oral premalignant and malignant lesions using digital pathology in addition to cancer immunology and immune therapy.

Current Research

Morphological and Immunological Characterization of HPV Positive Head and Neck Cancer and Pre-cancer

(Funded by Friends of Anchor, NHS Endowment)

The incidence of head and neck cancer (HNC) has increased in UK both in males and females and is still on the rise with the highest rates reported in Scotland. This increase is attributed to changes in risk factors such as alcohol and tobacco consumption in addition to human papilloma virus (HPV) infections. HPV infection affects younger age groups and is therefore associated with HNC and premalignant lesion diagnoses at younger ages than traditionally reported.

Premalignant lesions predispose to malignant transformation and should be monitored to aid in the early detection of malignant transformation. Classically, premalignant lesions were classified into mild, moderate and severe epithelial dysplasia. This classification system suffered from subjectivity leading to noticeable discrepancies in inter-and intra-examiner consistency in diagnosing these lesions. Therefore, there is a move towards simpler more reproducible classification systems that divide premalignant lesions into low and high grades.

To aid the classification dilemma and ultimately improve the ability to predict malignant changes, several studies were performed that applied reproducible and objective parameters to analyse tissue sections from different pathological entities. Our group used morphological features such as the complexity of the epithelial connective tissue interface (ECTI), and descriptors of cell shape and size  to characterize oral cancer and precancer in addition to normal oral mucosa (Abu Eid and Landini, 2003; 2005). It is hoped that such criteria can be implemented in the design of new classification systems that will better predict  malignant transformation potential and provide guidelines for clinical management.

Despite advances in treating HNC, the mortality rate is still high which is mainly due to the late diagnosis of these cases. Therefore, there is great need for developing diagnostic tools that aid in early detection. Additionally, the development of novel therapies is essential. Among the advances in cancer treatment, cancer immunotherapy is one of the most important developments. HNCs positive for HPV are candidates for cancer immunotherapy. Our group has reported promising anti-tumour efficacy in TC-1 murine mouse model, which expresses HPV E7 using different formulations of HPV E7 peptide vaccines, including different adjuvants (Abu Eid et al., 2014) and listeria based E7 vaccine (Mkrtichyan et al., 2014). The anti-tumour therapeutic efficacy of these vaccines was significantly enhanced when combined with PI3k/Akt pathway inhibitors (Abu Eid et al., 2014; 2017; Ahmad et al. 2017). Furthermore, in cervical cancer patients, we showed that Pre-Immature Dendritic Cells pulsed with HPV E7 are capable of inducing specific immune responses against the E7 peptide despite the advanced disease (Rahma et al., 2014). We further showed that combining HPV E7 vaccines with antibodies targeting PD-1 enhance  anti-tumour therapeutic efficacy through modulating the tumour microenvironment (Mkrtichyan et al., 2014). It is therefore integral to understand the role of PD-1 and its ligands (PDL-1 and PDL-2) in HNC (Shrimali et al., 2015).

To further the research into HNC immunotherapy and the classification of premalignant lesions, full understanding of the immune response in addition to complete characterization of morphological changes in HPV positive and negative premalignant and malignant lesions is crucial.

Modulators of T Cell Function 

Collaboration with Dr Frank Ward, University of Aberdeen

(Funded by Friends of Anchor)

Cancer immunotherapy is among the most important developments in cancer treatment. Despite its impressive successes, the response in patients is often limited and short lived. This is due to factors that hamper the immune response against tumour cells. 

Regulatory CD4 T-cells (Tregs) are major contributors to the suppressive tumour microenvironments and immune modulators that selectively mitigate these cells are needed. 

The expression of co-inhibitory molecules by tumour cells is another tumour mediated immune escape mechanism that leads to the suppression of effector T-cells. Immune checkpoint inhibitors that block the interaction between these co-inhibitory molecules and their receptors have shown remarkable results in enhancing anti-tumour therapeutic efficacy. 

Additionally, cancer immunotherapy is hindered by the short-lived anti-tumour effect due to the exhaustion of tumour-specific effector CD8 T-cells. The phenotype and differentiation status of CD8 T-cells have major influences on their function. There is intense interest in manipulating immune modulators to maximise their cytotoxicity and enhance their longevity as part of cancer immunotherapy. 

Small molecule inhibitors that target different signalling pathways within T cells have been used successfully to modulate T-cell responses by selectively inhibiting Tregs and/or generating superior antigen-specific CD8 T-cells with enhanced proliferative ability, survival and functional capability (Abu Eid et al. 2014, 2015, 2016, 2017). Furthermore, immune checkpoint inhibitors have proven successful in modulating the anti-tumour immune response. 

The aim of our work is to identify targets for selective modulation of immune cells while understanding the specific mechanisms that control T cell development and responses. Results will guide combination therapies with different immune modulators as part of cancer treatment.

Past Research

The Effect of Oligohydramnios on Tissue and Cellular Morphometry in the Developing Foetal Murine Lung. 

Collaboration with Dr Tanbir Najrana and Dr Juan Esteban-Sanchez, the Department of Paediatrics, Alpert Medical School of Brown University. Women & Infants Hospital of Rhode Island, USA

(Funded by the National Institute of General Medical Sciences of the National Institutes of Health Department of Pediatrics; Kilguss Research Core of Women & Infants Hospital of Rhode Island).

Oligohydramnios resulting from membrane ruptures can cause pulmonary hypoplasia in humans. This has been confirmed experimentally in different animal models and attributed to the decrease in lung distention as result of a decrease in lung fluid in the developing air spaces.

We have characterized a mouse model of pulmonary hypoplasia secondary to severe oligohydramnios and reported significant changes in the differentiation of different cell types, in particular Type I cells, where the level of T1-α (a marker for Type I cells) was significantly reduced in OH both at the mRNA and protein levels. Furthermore, we found that oligohydramnios affects vasculogenesis and apoptosis without altering cell proliferation. Interestingly, we reported a major decrease in developing lung spaces and a significant decrease in cell size and a change in cell shape as a result of oligohydramnios using different descriptors of particle size and shape (Najrana et al., 2016; 2017).

Currently, we are looking into different rescue models for foetal pulmonary hypoplasia using different murine models.

Knowledge Exchange

Fractals in Biology and Medicine. Pecha Kucha Talk. Explorathon 17, Aberdeen, September 2017.

Funding and Grants

1. Cancer Research UK, Early Detection and Diagnosis Project Award: “Integrating Raman spectroscopy and digital pathology as a novel tool for objective grading of oral epithelial dysplasia”. Duration 24 months (February 2023-January 2025). Value: £253,520.38. Role: Principal Investigator.
2. University of Aberdeen Knowledge Exchange and Commercialisation (KEC) Award: “Preliminary cytokine bead array data to support further development of an anti-sCTLA-4 antibody, 8-B12, as a novel checkpoint inhibitor therapy”. (2022). Value £7,100. Role: Co-investigator.
3. Grant for Research Pilot Studies from Friends of ANCHOR: “The oro-intestinal microbiota as a novel marker for early detection and target for prevention of oral cancer.” Duration 12 months (July 2022-June 2023). Value: £14,981.40. Role: Co-investigator.
4. University of Aberdeen Pump-priming for interdisciplinary research initiatives: “Geology Meets Biology”. (2022). Value £9,825. Role: Co-investigator.
5. NHS Endowment research grant from NHS Grampian: “Digital pathology as a predictive tool of the response to first line treatment in oral lichen planus.” 20/012. Duration: 24 months (April 2021-March 2023). Value: £11,986.17. Role: Principal Investigator.
6. Grant for Research Pilot Studies from Friends of ANCHOR: “Using Raman Spectroscopy for the early detection of oral cancer”. RS 2020 06. Duration: 21 months (2021-2022). Value: £12,055.75.00. Role: Principal Investigator.
7. COVID-19 Research Grant, Medical Research Scotland (MRS): “Methods for reducing the risk of SARS-cov2 associated cytokine storms in COVID-19 patients”. Duration: 6 months (September 2020-March 2021). Value: £19,356. Role: Co-Investigator.
8. Grant for Research Pilot Studies from Friends of ANCHOR: “Targeting the PI3K/Akt/mTOR pathway to modulate the immune response in COVID-19” Duration: 24 months (2020-2022). Value: £15,000.00. Role: Principal Investigator.
9. University of Aberdeen Global Challenge Research Fund Internal Pump Priming Fund: “Geographical Information Systems for mapping oral cancer incidence and high risk behaviours in Sri Lanka”. (2019). Value £10,000. Role: Principal Investigator.
10. NHS Endowment research grant from NHS Grampian: “Analysis of soluble CTLA-4 as a novel immune evasion strategy by cancers”. 18/24. Duration: 12 months (April 2019-March 2020). Value: £10,090. Role: Co-Investigator.
11. Grant for Research Pilot Studies from Friends of ANCHOR: “Enhancing the anti-tumour efficacy of BRAF inhibitor therapy with immune modulators”. RS 2018004. Duration: 24 months (2018-2020). Value: £14,469.00. Role: Co-Principal Investigator.
12. NHS Endowment research grant from NHS Grampian: “Characterisation of the microscopic and immune profiles of premalignant oral lesions”. 17/042. Duration: 18 months (April 2018-Septemebr 2019). Value: £11,913.10. Role: Principal Investigator.
13. Research grant from TENOVUS SCOTLAND: “Characterisation of cytotoxic T lymphocyte antigen 4 (CTLA-4) expression and function in tumour cells”. G17.11. Duration: 12 months (January 2018-December 2018). Value: £11,991.00. Role: Co-investigator.
14. Grant for Research Pilot Studies from Friends of ANCHOR: “Morphological and Immunological Characterization of HPV Positive Head and Neck Cancer and Pre-cancer”. RS17007. Duration: 24 months (2017-2019). Value: £9,719.00. Role: Principal Investigator.
15. Research grant from the Deanship of Academic Research at the University of Jordan to fund the research: “Drug Induced Gingival Enlargement: A Clinical, Histological and Molecular Comparison between Different Drugs.” December 2007. Value JD 9,900. Role: Principal Investigator.

Teaching Responsibilities

Contribution to courses at the Dental Institute

Teaching in the BDS course 

1. Oral Histology (BDS2)
2. Lead for Oral Biology
3. Student Seminars (BDS5)

Teaching in the Dental Technology course

1. Oral Biology (DT1)
2. Course coordinator for the Oral Anatomy and Physiology Course (DE1502)

Postgraduate Taught Programmes

1. MSc in Special Care Dentistry 
2. MSc in Advanced Restorative Dental Practice Dissertation (DE5044)

• Project supervisor and Research tutor

Contribution to other programs

 Medical course MBChB

• Immunology of Endocrine Disease (Year 2)
• Immunology lectures (Year 3)

Immunology Honours IM4007 Course

• Immune evasion: Cancer
• Scientific paper assessment

Advanced Immunology IM4005

• Current Topics in Immunology
• Regulatory T Cells/ Tumours and Inflammatory Disease

Applied Immunology Human Health IM3502

• Immunity to viruses

Fundamentals of Immunology IM3501

• Regulatory T cells

Microbes, infection and immunity BI25M5

• Evading the immune system

MSc in Immunology and Immunotherapy

• Immunogenetics of cancer
• Assessment of student presentations

MPH Master of Public Health

• Student supervision
• Thesis marking

MSc Global Health and Management

• Marking assessments

Research Tutorials Course (for masters students) MB5518

• Presenter

Fundamentals of Research Design Course for taught MSc Programs (FORD) (PU5027, PU5052)

• Tutor

Industrial Placement (BT5007)

• Tutor

Non-course Teaching Responsibilities

• Regent as part of the regent scheme at the Institute of Dentistry
• Mentor as part of the SUCCESS scheme at the School of Medicine, Medical Sciences and Nutrition