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
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
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
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
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
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
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