Identification of an exosomal miRNA signature in newly diagnosed essential hypertensive adults

Background: Hypertension is a leading risk factor for cardiovascular disease (CVD) and premature death globally. Less than half of adults with hypertension are properly diagnosed and treated, highlighting a critical gap in current healthcare practices. The limitations of existing blood pressure measurement methods make it challenging to detect early cases of hypertension, which are often asymptomatic and, consequently, commonly undetected. This indicates the need for improved diagnostic and treatment strategies, particularly through precision medicine approaches. MicroRNAs (miRNAs) serve as master regulators of gene expression and are transported extracellularly by exosomes in various body fluids including plasma. Exosomal miRNAs have been implicated in hypertension development and have potential as non-invasive disease biomarkers. However, the profile of exosomal miRNA in a multi-ethnic population of essential hypertensives has yet to be elucidated. Aim and objectives: This study aimed to investigate potential biomarkers of hypertension to enhance early detection. The objectives of this study were to screen and validate the differentially expressed exosomal miRNA profiles in essential hypertensive adults and identify their predicted targets and associated pathways. Methods: Plasma exosomes were isolated and characterised. Total plasma exosomal RNA were extracted from ethnically Chinese and Malay stage 1 essential hypertensive and normotensive adults (30 to 55 years old). Samples were subjected to small RNA sequencing, differential expression analysis, target prediction, and pathway enrichment analysis. The differential expression profile was validated with real-time quantitative polymerase chain reaction (RTqPCR). The diagnostic value of the differentially expressed miRNAs were assessed. Enriched pathways and gene ontologies of predicted miRNA targets were compared against systemically dysregulated pathways to validate its biological function. Results: Characterisation of plasma exosomes showed preferential release of medium- to large-vesicles with a significantly increased number of particles between 150 to 200 nm (P = 0.021) and an increased mean size (mean = 104.7 ± 19.3; P = 0.036) in hypertensives. Immunoblotting showed significantly xix reduced CD9 expression in hypertensives. The combination of hsa-miR-184, hsa-miR-432-5p, hsa-miR-1-3p, and hsa-miR-1246, along with BMI, efficiently identified hypertension risk with the highest area under the curve (AUC = 0.966, P < 0.0001) for the receiver’s operating characteristic (ROC) analysis. The miRNA signature together with systemically dysregulated pathways further highlighted the convergence of aberrant metabolic pathways in the development of hypertension. Conclusions: This study provided the first comprehensive exosomal miRNAome in a multi-ethnic population of newly identified essential hypertensive adults. The differentially expressed miRNAs in essential hypertension provided leads for further validation and may provide unbiased insights into mechanisms involved in the early stages of hypertension, facilitating novel biomarker discovery or therapy development to alleviate the burden of CVDs

The illusion of choice: barriers faced by mothers with young children in Kazakhstan in re/entering the labour market: an analysis with the concept of defamilisation

This thesis explores women’s experiences when combining motherhood and paid work, and the role that the state, the markets and the family play in this. The theoretical framework is based on the concept of defamilisation in order to explain the extent to which and the way in which three sectors, the state, the labour market and the family, impact the defamilisation of women (Lister, 1994). Mothers of young children, not only in Kazakhstan but in general need support from the state, employers and family (Dugarova, 2016). The state plays a key role not only in ensuring acceptable standards of living for people by decommodifying them from the labour market (Esping- Andersen, 1990; 1999), but it may also provide support to mothers of young children by defamilising them through assistance with childcare and allowing them to have free time to enter paid work (Lister, 1994; Chau and Yu, 2022). While there is research published on gender inequality in Kazakhstan in terms of gender-based discrimination and wage gender gap they experience (Omarova et al. 2017; Khamzina et al. 2020; Mukhamadiyeva et al. 2019; Bidaishiyeva et al. 2018), there are few if any empirical studies carried out on defamilisation and motherhood penalty in Kazakhstan. This thesis therefore makes an original contribution by filling this gap in research. Through semi-structured focus group discussion and secondary research, it explores whether and how the state, the markets and the family assist or hinder women from (re)entering paid work and their impact on defamilisation. This data was analysed through an interpretive approach and thematic method, and utilising an insider positionality approach (Geene, 2010; Wilson et al, 2022). The data collection for this research took place in December 2021 and May 2022 in Almaty and Turkestan, cities located in South of Kazakhstan. The findings show that despite conservative values and beliefs in the importance of traditional gender roles, a pragmatic rationale for having dual-earner household and women choosing to enter paid work for financial needs prevail. The financial situation in families plays a decisive role in women’s decisions to find paid work and commonly women whose partners earn generously postpone entering the labour market for an indefinite time. The findings also suggest that the state's lack of support for mothers of young children pushes them to seek paid work, but due to difficulties faced there to enter and retain, women remain dependent on their families. The traditional lifestyle of living in multigenerational households mean women are engaged in social exchange with members of extended family and receive support with childcare in return for unpaid domestic services. Therefore, the state, the labour market and the family present a complex environment for mothers of young children engaging in paid work, resulting in a strong pull from the family that ultimately hinders them from being able to maintain an acceptable living standard independently of their families

Targeting DNA damage repair pathways in breast and ovarian cancers

Background DNA damage could be due to many endogenous and exogenous agents producing DNA lesions which block the transcription process affecting the gene expression, cell growth and survival. The DNA damage response network detects the damage and any flaw in the network including defects in DNA repair systems can lead to cancer. Thus, drugs targeting DNA repair systems relying on this concept are under development with various drug monotherapy or combination therapies. Targeting DNA repair genes of nucleotide excision repair system (XAB2) and Fanconi anaemia repair system (FANCD2 and FANCA) for synthetic lethality is a novel strategy for treating breast and ovarian cancers. Hence, the synthetic lethality concept is an exciting area for future research. Methods In this study, XAB2 expression in the breast cancer cohort was investigated. Cisplatin and olaparib sensitivity was evaluated in a panel of gene XAB2, FANCD2, FANCA deficient and proficient breast and ovarian cancer cell lines. XAB2 expression and the clinicopathological outcomes were investigated in the ovarian cancer cohort. The gene knockdown and cisplatin sensitivity were tested in platinum-sensitive and platinum-resistant ovarian and breast cancer cell lines. Functional studies for wild and knockdown genes such as PI FACS-cell cycle and Annexin V-apoptosis assay were performed. Results In breast cancer cases, results showed that a low XAB2 nuclear expression was associated with a high tumour grade and poor breast cancer-specific survival (BCSS) in patients. In invasive breast cancer, low XAB2 expression had clinicopathological associations with aggressive forms of breast cancer. In gene knockdown, cisplatin and olaparib were synthetically lethal in gene-deficient breast cancer cell lines. In ovarian cancers, XAB2 was significantly overexpressed in serous adenocarcinoma. The low XAB2 expression was significantly linked to good overall survival. The cisplatin was selectively toxic in gene-deficient platinum-sensitive ovarian cancer cell lines. The drug cytotoxicity was associated with double-strand breaks (DSBs) formation, cell cycle arrest and apoptosis in gene-deficient cells. The gene expression was a predictor of platinum sensitivity in ovarian cancer patients. The gene knockdown not only increased platinum sensitivity but also reduced invasion and migration in breast and ovarian cancer cell lines. The cisplatin drug was selectively toxic in gene-deficient breast and ovarian cancer cells. Conclusion Targeting DNA repair genes was an attractive synthetic lethality strategy and the chemoprevention in gene-deficient breast cancers. In ovarian cancers, gene deficiency was a biomarker for drug inhibitor sensitivity. It provided alternative synthetic lethality approaches for inhibitors in clinics. The gene depletion can re-sensitize ovarian cancer patients to platinum. Therefore, studying the expression of DNA repair proteins assisted in new drug therapies development and opened alternative treatment options

The social mobilisation of conservative Malays against the injured Leviathan: a case study of Perkasa and ISMA from 2008 to 2017

This dissertation provides a critical account on how a reactionary Malay-Muslim social movement (SM) emerged and developed in Malaysia between 2008 and 2017. It examines the political opportunity structure (POS) in Malaysia and how two social movement organisations (SMOs) – Perkasa and ISMA – mobilised conservative Malays for collective actions. It is found that the POS is largely determined by state capacity to repress regime opponents. From a previously “robust Leviathan,” the Malaysian state has been reduced to an “injured Leviathan” following the 2008 general election. Using a component of Slater’s (2010) ordering power model, I explain how the decline in repression brought about a cognitive liberation (McAdam, 1999) among conservative Malays and created an opening for a reactionary movement in civil society. To understand the SM development, I have used frame analysis to identify ketuanan Melayu and Islamic populism as collective action frames (CAF) for Perkasa and ISMA respectively (Snow & Benford, 1988). To further elucidate their collective agency, I investigate their “frame alignment strategies” (Snow, et. al., 1986) to mobilise conservative Malays by examining various discourses on the New Economic Model (NEM), the Trans-Pacific Partnership Agreement (TPPA), the Allah row and the Coalition of Malaysian NGOs in the UPR Process (COMANGO). They are found to have employed frame amplification in discourses on globalisation and frame bridging for identity politics. Finally, this dissertation applies the concepts of injured Leviathan, frame amplification and frame bridging to make sense of contemporary Malaysian politics

Osteoarthritis and multimorbidity in male retired professional footballers compared to men in the general population

Background: Football is one of the most popular sports world-wide. Professional footballers are at higher risk of injuries of lower limb joints and the head due to the nature of the game. This can lead to short- and long-term health consequences such as osteoarthritis (OA) and cognitive disorders. However, whether footballers are at higher risk of developing knee pain, multimorbidity and OA of the foot/ankle after retirement remains unknown. Objectives: [1] to systematically review published observational studies on multimorbidity and long-term conditions in professional footballers only or compared to the general population; [2] to examine the incidence of knee pain in male retired professional footballers (referred to as footballers) compared to men in the general population (referred to as controls) and associated risk factors in each group; [3] to examine the association between knee pain at baseline and incidence of multimorbidity at follow-up in footballers and controls; [4] to examine the incidence of multimorbidity in footballers compared to controls and associated risk factors in each group; and [5] to examine the association between radiographic knee OA and foot and/or ankle OA in footballers and controls. Method: A systematic literature review of observational studies for multimorbidity in professional footballers was undertaken in 3 databases in addition to the Google Scholar until 31st December 2021. The Newcastle-Ottawa Scale was used to assess the quality of the observational studies. The prevalence, incidence and associated risk factors of multimorbidity, or specific long-term conditions were extracted or calculated for footballers compared to the general population. The pooled prevalence of multimorbidity and each long- term condition and 95% confidence interval (CI) were calculated. An observational cohort study was undertaken in retired male professional footballers and aged matched general population controlled men aged ≥ 40 years using a postal questionnaire to examine the incidence of knee pain and multimorbidity over the 6-year period, and radiographic examination in a sample from each group to examine the association between radiographic knee and foot/ankle OA. Knee pain was defined as anterior knee pain experienced for most days of the previous month using body pain mannequin. Multimorbidity was defined as having at least 2 long-term conditions in an individual from 45 conditions included. Risk factors for incident knee pain and multimorbidity were examined per group. Radiographic knee OA was defined using Kellgren and Lawrence grade ≥ 2 in either tibiofemoral or patellofemoral compartments irrespective of the side. Foot and/or ankle OA was defined using the La Trobe Atlas (i.e., the presence of at least ≥2 in osteophytes (OP) plus joint space narrowing (JSN) at any joint of foot/ankle). Incidence (%) of knee pain and multimorbidity was estimated for both groups and adjusted odd ratio (aOR) and 95% CI was calculated using logistic regression. Risk factors for knee pain and multimorbidity were examined using multivariable logistic regression. OR and 95% CI was calculated using logistic regression for association between radiographic OA at the knee and foot/ankle joints. Correlation coefficient β was calculated using linear regression for summated radiographic OP and JSN scores at both sites. Results 56 studies (42 cross-sectional studies, 4 case-control studies, 8 cohort studies, and 2 mixed design studies (cross-sectional and case-control)) were eligible for the systematic review from 18 different countries. There were 24 studies for footballers versus controls, and 32 studies for footballers only. The age ranged from 18 to 93 years old. Quality of included studies was regarded as medium quality. Most of the retrieved studies focused on a single long-term condition, and some studies reported on more than one long-term condition but did not report on multimorbidity. OA was found to be the most common condition being investigated, followed by neurodegenerative diseases, hip or knee pain, psychological and cardiovascular diseases. Methods used to examine long-term conditions or their risk factors were highly heterogenous. Of the 14 studies provided prevalence of knee OA in footballers, the pooled prevalence was 31% in male retired footballers (95% CI 20 – 42%). Of the 6 studies provided prevalence of knee OA, the pooled prevalence was 26% in male controls (95% CI 7 – 44%). Of the 4 studies provided prevalence of knee pain in footballers, the pooled prevalence was 53% in male retired footballers (95% CI 0 – 100%). Of the two studies provided prevalence of knee pain, the pooled prevalence was 27% in male controls (95% CI 26 – 28%). Of the 4 studies provided prevalence of ankle OA, the pooled prevalence was 9% (95% CI 7 - 10%) in male retired footballers. Of the 7 studies provided prevalence of hip OA in footballers, the pooled prevalence was 7% (95% CI 4 - 11%) in male retired footballers. Of the two studies provided prevalence of hip OA in controls, the pooled prevalence was 2% (95% CI 1 - 4%) in controls. Joint injury was the major risk factor associated with the increased risk of OA in footballers. For neurodegenerative disease, only one comparative study was identified from the literature, the incidence of neurodegenerative disease was higher in footballers (5.0%) compared to the general population controls (1.6%) over 18 years follow-up (p<0.001). Playing position (midfielder and defender), head injury and career duration might increase risk for neurodegenerative disease. For the following conditions, only one comparative study was identified from the literature, the prevalence of self-reported acute myocardial infarction was 3.08% in male retired footballers and 9.46% in controls (p<0.001), hypertension was 22.98% in footballers and 34% in controls (p<0.001), and diabetes was 3.77% in footballers and 11.47% in controls (p<0.001). Of 486 footballers and 610 controls with data collected at two waves, 222 footballers and 402 controls were at risk for knee pain. There was no significant difference in the incidence of knee pain between footballers and controls (24.0% and 28.8% respectively, p=0.18) (aOR 0.77, 95% CI 0.52 – 1.16). Whilst body mass index (BMI) (aOR 1.17, 95% CI 1.04 – 1.31) and football-related knee injury (aOR 2.42, 95% CI 1.22 – 4.79) were risk factors for incident knee pain in footballers, BMI (aOR 1.08, 95% CI 1.01 – 1.14) and higher socioeconomic status (aOR 0.88, 95% CI 0.81 – 0.95) were associated with incident knee pain in controls. No association was observed between knee pain at baseline and incidence of multimorbidity at follow-up in footballers and controls. A total of 317 footballers and 362 controls were at risk for multimorbidity. The incidence of multimorbidity was lower in footballers (37.5%) than controls (52.0%) (p<0.001) (aOR 0.64, 95% CI 0.45 - 0.89). Whilst age (aOR 1.04, 95% CI 1.01 – 1.07), the presence of one condition at baseline (aOR 2.98, 95% CI 1.78 – 4.99) and analgesic use (aOR 2.88, 95% CI 1.53 – 5.40) were risk factors for incidence of multimorbidity in footballers, age (aOR 1.05, 95% CI 1.03 – 1.08), the presence of one condition at baseline (aOR 2.73, 95% CI 1.73 – 4.31) and higher socioeconomic status (aOR 0.88, 95% CI 0.81 – 0.95) were associated with the incidence of multimorbidity in controls. A total of 72 footballers and 147 controls underwent radiographs for both knee and foot/ankle joints. The association between knee OA and foot/ankle OA was not statistically significant in footballers (aOR 4.13, 95% CI 0.72 – 23.66; p=0.111), but was significant in controls (aOR 2.57, 95% CI 1.01 – 6.53; p=0.046). Similar finding were observed using the linear regression analysis for summated radiographic scores of OP and JSN. Conclusions Although professional footballers may be more likely to develop OA and neurodegenerative disease, they may be less likely to develop other long-term conditions, such as diabetes and cardiovascular diseases, and multimorbidity. In addition to the constitutional risk factors such as BMI, football-related head and joint injuries may explain the additional risks of OA and neurodegenerative disease. However, the general health and physical fitness may also explain the lower risk of other conditions and multimorbidity in footballers compared to controls. The results of this PhD project suggest the preventative strategy should be tailored to the population specifications to mitigate the specific risks and improve the general health status

A lived and living UK gaming oral history: untangling narratives of resistance and resurgence in videogame space

This thesis critically examines gaming subjectivities, games culture, and ideologies that circulate within videogames and their communities. Via a series of oral history interviews, and with an emphasis on a person-centred approach, this research scrutinises the bleed between gaming culture and far-right belief systems, evidenced by issues like identity policing and online harassment. However, rather than focusing on the extreme edges of games culture, which movements of organised harassment like Gamergate made overt, this work considers the gaming mainstream and the experiences of ostensibly “normal” people within gaming; what they think, and how they feel, about videogames, gamer identity and games culture. As well as examining challenges games culture faces, this work considers how we can resist resurgent discourses within game space. Through a feminist, queer point of view – that is grounded in the thesis’ theoretical approach – this research seeks to not only understand the ideological knots and contradictions that far-right discourses operate through in gaming, but how we might begin to untangle them. This untangling is facilitated by an overarching concern and implementation of affect as a theoretical and analytical framework; emphasising the importance of how videogames make people feel. Part of this emphasis is framing gamer as an “affective” identity. In other words, gamer identity as made, maintained and disturbed through feeling and emotion. I am concerned with how videogames are meaningful to the interview participants here, players in gaming communities, players outside of gaming communities, and the stereotypical gamer. Examining this meaningfulness requires understanding how we relate to gaming histories, as well as how we think about gaming in the present, which has implications, in turn, for how we do or do not connect with gamer identity. What is at stake in conversations about videogames and gaming culture, the stories, opinions and thoughts that interview participants articulated, is often more than just videogames; it is about access to spaces, belonging to a community, how we perceive our own identity, and our ability to play and have fun. Ultimately, this research is about people in gaming spaces, and how videogames are meaningful to them in ways that are inherently subjective and personal. This subjectivity is reflected in the research’s interview-led approach. This thesis contends with what is difficult about videogame culture but is also concerned with the people who exist within and move through it, and how they feel about videogames, and why this matters

Development of landslide tolerable and acceptable risk criteria for Malaysia

Landslide tolerable and acceptable risk criteria are strongly governed by utilitarian concerns i.e. financial power and the need for development and should be developed locally with historical landslide inventory, public perception, and engineering aspects being considered. The risk criteria of Hong Kong and that of the Australian Geomechanics Society are widely employed in many countries. The present study aims to develop and improve the landslide tolerable and acceptable risk criteria for Malaysia by taking into considerations of qualitative and quantitative inputs from various stakeholders. Based on the compiled landslide inventories, the Frequency-Number of fatalities (F-N) curve of Malaysia established from the present study have a similar slope gradient with those of Italy, Colombia, and Hong Kong. The F-N curve is a graphical tool (typically expressed on a log-log scale) used to depict the level of societal risk associated with a particular activity or project, which, in the present study, is landslides. As for the findings from the questionnaire surveys and interviews with landslide experts, public (non-experts) generally expressed the lowest acceptance in landslide risk for all scenarios (from low to high risk), whereas the experts were willing to accept a higher landslide risk as they understand that an ideal low landslide risk environment is not feasible under the current Malaysian scenario. Gender, occupation and educational level were the significant demographic factors influencing landslide risk acceptability in Malaysia. Modifications were proposed to the existing landslide risk criteria with a lower acceptance towards death upon taking into consideration findings from the present study. To demonstrate the application of the newly developed criterion and runout model, quantitative risk analyses (QRA) were performed to quantify landslide risk for a real-life case study. An important part of QRA concerns the development of a simple yet reliable model for predicting the impact / consequence of a landslide. A new empirical model for landslide runout estimation in Malaysia was proposed based on historical landslide data. The reliability of the proposed model was verified through a reasonable agreement between the actual runout and predicted values. Gumbel analysis was utilized to obtain the extreme rainfall scenario with a 10-year return period. It should be noted that Gumbel analysis is typically conducted for the probability distribution of extreme value in hydrologic studies for prediction of maximum rainfall. Seepage and probabilistic slope stability analyses were carried out to determine the probability of landslide occurrence of the studied slope. Using the newly developed empirical model, the runout of the landslide was predicted. The outcomes included a quantification of risks posed to elements within the runout path, such as houses and residents. The findings offer a quantitative estimation of the annual probability of fatalities for people. A F-N curve was employed to articulate the societal risk associated with this specific slope in the case study, which was then compared against the newly established risk criterion. These results carry significant societal implications and will furnish decision-makers and regulators with valuable insights for devising risk mitigation strategies for both existing slopes and forthcoming developments

“You might judge me!”: parents’ mobile device use with young children with SEND at home

Background: Previous research has shown that young children’s ownership and use of mobile devices (smartphones and tablets) at home is growing globally. This has led many researchers to examine the possible effects of these devices on the development of young children. A growing body of research has explored screen device use of typically developing children and their parents’ attitudes and practices towards this, and a few studies have focused on children with autism spectrum disorder (ASD). However, it is still unexplored how young children with special educational needs and disabilities (SEND, e.g., children with Down’s syndrome, children with learning disability) are using mobile devices at home and parents’ attitudes and practices regarding this use. This study examined mobile device use by young children with SEND (under 7 years) at home and parents’ perspectives and practices regarding mobile device use in the United Kingdom (UK). Methods: This study adopted the explanatory sequential research design, a mixed-method research approach, which consisted of two stages. In the first stage, 39 parents of young children with SEND completed an online survey on their children’s mobile device use at home and their attitudes and practices on this use. In the second stage, 9 semi-structured online interviews were conducted with parents who completed the survey in the first stage and were interested in attending a follow-up interview via Microsoft Teams. While the participants of the survey were more diverse in terms of their children’s conditions, interviews were conducted with parents of children with Down’s syndrome (n=6) and with Autism (n=3). The quantitative data collected from the surveys were analysed using descriptive statistics, and qualitative data gathered from the interviews were analysed using thematic analysis. In the present study, Cultural-historical Activity Theory (CHAT) was adopted as a theoretical framework that provided rich insights into the data analysis by highlighting the key role of the broader context in affecting parents’ attitudes and practices regarding mobile device use with their children. Results: The survey results showed that almost 82% of children with SEND were using a mobile device at home. Specifically, 71.8% of responders reported that their children with SEND were using a tablet, and 48.7% reported smartphone use at home. Overall, parents had an overwhelmingly positive view of their child’s mobile device use. 71.7 % of parents agreed that the use of mobile devices is beneficial for early learning and development. Nevertheless, 61.5% of surveyed parents thought that the overuse of mobile devices has a negative effect on children’s social interaction. Almost all of the interviewees acknowledged that the overuse of mobile devices may have negative effects on their children and that parents should limit their children’s mobile device use. Parents adopted some mediation strategies to prevent the negative effects of screen use on their children, such as setting time limits, co-use of devices, and monitoring children’s device use. The qualitative results showed that parents use mobile devices with their children for various purposes, including parenting (babysitting), entertainment, and education. Participants highlighted the educational benefits of mobile device use, and they use mobile devices with their children to facilitate language and speech development; teach Makaton signs; support early literacy development; and support numeracy development. Conclusion: Mobile device use was high among young children with SEND with tablets being the most common mobile device used at home. Parents had mixed feelings, neither totally positive nor negative, about the use of mobile devices by young children with SEND. Furthermore, it seems that young children's parents tend to use mobile devices as an instrumental tool in their childrearing practices, which has been considered part of 21st-century parenting in the literature. Although there were some similarities between parents of children with SEND and parents without SEND regarding their mobile device use with their child, there were some attitudes and practices that were unique to parents of young children with SEND. In line with CHAT, the findings of the present study showed that parents' (subject) mobile device use with their young children with SEND is shaped by the availability of mobile devices (tool), parents’ motivations/intentions (object: Educational, entertainment, babysitting), rules (e.g., approved apps and content, time limit), community (home environment, charities, media, schools), division of the labour (children with SEND, educators, health practitioners)

Regulation of ABCG2 through interactions with Alpha-1-Acid Glycoprotein and EMMPRIN

The human ABCG2 transporter, a member of the ATP-binding cassette (ABC) transporter superfamily, plays a crucial role in the efflux of various substrates, including chemotherapeutic drugs from cells. Its involvement in drug efflux has been extensively associated with multidrug resistance (MDR) in cancer cells, highlighting the pressing need for a deeper understanding of ABCG2 regulation. One way that proteins are regulated is through interactions with other proteins, impacting their function. The thesis investigated the possible role of alpha-1-acid glycoprotein (AAG) as an extracellular acceptor of ABCG2 substrates, therefore accelerating efflux. Secondly, the thesis studied whether extracellular matrix metalloproteinase inducer (EMMPRIN) acts to stabilize ABCG2 and increase its expression or stability. ABCG2:AAG interactions were investigated through functional time- course transport assays using stably transfected HEK293T-sfGFP- ABCG2 cells and rates of efflux were measured and compared. Semiquantitative analysis of HEK293T-sfGFP-ABCG2 cells co- transfected with EMMPRIN were studied for ABCG2:EMMPRIN interactions. Addition of AAG was not found to have increased the rate of mitoxantrone efflux by ABCG2. Co-expression with EMMPRIN did not result in increased ABCG2 expression in whole cell lysates. Though results from experiments were inconclusive in relation to the proposed hypotheses, groundwork has been laid out for future protein biophysical work that enables investigation of ABCG2 protein-protein interactions