Externally funded projects

Al Jalila Foundation

Project1-Title: Studying the phosphorylation status of ShcD in melanoma upon oxidative stress: An evidence for new therapeutic target in melanoma

Investigator: Samrein Ahmed
Co-Investigators: Dr. Wael  M.  Abdel-Rahman Hassan and Dr. Ahmed Taher El-serafi

Background:

The pigmented skin cancer, Melanoma, prevalence is increasing progressively. However, there are variable treatment modalities for melanoma; resistance to the treatment is an inevitable event, which urges the importance of finding new potential therapeutic targets. ShcD is a newly identified protein was found to be upregulated in 50% of metastatic melanoma cells. In vitro studies revealed that ShcD induces melanoma cell migration and tumourgenesis; hence it was suggested to be a potential therapeutic target for treating melanoma.  The molecular mechanisms of how ShcD mediates tumourgenesis are still obscure. Preliminary data showed that upon hydrogen peroxide treatment, ShcD gets phosphorylated and associates with phospho-ERK. P-ERK/ShcD association might have role in triggering antiapoptic signal providing melanoma cells with a survival signal to resist death signal caused by oxidative stress. UV exposure is one of the known factors that plays a weighty role in melanoma pathogenesis. UV is known to cause DNA damage via forming pyrimidine dimers as well as by elevating the intracellular reactive oxygen species. A new proposed anti-cancer drug, Shikonin, was found to kill cancer cells by increasing the intracellular reactive oxygen species.

Hypothesis: Upon oxidative cellular stress, ShcD phosphorylation plays an important role in melanoma cell survival and migration.

Project2-Energy Restriction as a Novel Approach Targeting Cancer Stem Cells Multi-drug Resistance

Investigator: Dr. Hany Omar

Co-Investigator: Prof. Taleb Al Tel

Project summary


This project is based on the hypothesis that the use of Energy Restriction Mimetic Agents (ERMAs) with classical anticancer agents would not only selectively target cancer cells but also limits the availability of energy needed for ATP-driven efflux transporters and so inhibits the multi-drug resistance (MDR). In addition, we postulated that the maximal benefit can be exploited with the combination of ERMAs with other chemotherapeutic agents which are candidates for MDR to induce mechanistic synergy in resistant cancers.

 

Project3-5-Aminosalysilate-4-thiazolinone hybrid derivatives as novel anticancer agents: molecular mechanisms and in-vivo safety and activity

Investigator: Dr. Rafaat Al Awady

objectives:

 This study is designed to investigate the molecular mechanisms of four 5-aminosalicylate-4-thiazolinone hybrid molecules that have been recently synthesized and have shown promising anticancer activity on different types of cancer cells with minimal activity on normal cells  (figure 1, Abdullah et al 2016). In addition, the in-vivo effects and safety of these compounds will be tested on xenograft animal models. 

Project4:Stress and Women's Health: A Population-Based Study on Prevalence of Stress, Its Determinants, Its Association to Quality of Sleep, Physical Activity, Dietary Habits among Healthy Adult Women Living in The United Arab Emirates

Research Team:  

Dr. Wegdan Bani issa (PI), College of Health Sciences, UOS

Dr.  Shamsa Al Awar, College of Medicine, UAEU

Dr. Rani Samsudin, College of Dentistry, UOS

Dr. Hadia Radwan, College of Health Sciences, UOS

Dr. Farah Al-Marzooq, Research Institute of Medical and Health Sciences, UOS

Mrs. Arwa Al Shujairi, Research Institute of Medical and Health Sciences, UOS

 Background:

Mental health is important indicator of good health. Prolonged stress in women can lead to serious health problems, such as heart diseases, hypertension, cancer, diabetes, depression, anxiety disorder, and other illnesses. Stress response is mainly controlled by the hypothalamic-pituitary-adrenal axis which has a central role in regulating many homeostatic systems including the immune system, digestion, mood and emotions, energy storage and expenditure. The normal homeostasis in the human body is usually regulated by several hormones such as cortisol and melatonin.

Project5:Evaluating the Anti-Carcinogenic Potential of Biologically-Driven Intracellular Iron Depletion

Investigator: Dr. Moawiah Abdel Haq

Project summary:
Over the last few years, several studies have shown that breast cancer cells exhibit increased levels of oxidative stress evidenced by abundant labile iron pools, increased levels of intracellular ferritin, hepcidin and transferrin receptor (CD71) and reduced ferroportin (FPN) expression.  Increased iron availability in cancer cells enhances further proliferation, oxidative stress, and accumulation of genetic/epigenetic errors.  This has formed the basis for iron chelation therapy in certain forms of cancer.  Despite intensive basic and clinical research work with chemical chelators however, the efficacy and safety of such an approach in cancer remains debatable.  Hence, there is a need to develop biological modifiers capable of manipulating iron homeostasis and depleting intracellular iron without rendering the host iron deficient.  In this context, recent work by our group has suggested that elevated levels of estrogen alter intracellular iron homeostasis.  In that, treatment of MCF-7 breast cancer cells with high doses of estrogen (5-20nM) has resulted in a significant upregulation of Hif-1α associating with a significant reduction in hepcidin synthesis.  Additionally, treated cells showed a pronounced increase in FPN expression coupled with reduced intracellular (exchangeable) iron content.  Estrogen-treated cells also showed a significant reduction in TfR1 and TfR2 expression, suggesting that treated cells may not be able to compensate for lost iron as TfR1 is the main receptor that imports extracellular iron. Collectively therefore, estrogen-receptor engagement may induce intracellular iron depletion. The proposed work aims at assessing whether estrogen receptor engagement (by estrogen or ER agonist) induces intracellular iron depletion and whether iron depletion in this manner precipitates anti-carcinogenic consequences such as reduced oxidative stress, limited cellular proliferation and increased apoptotic potential.