Iron Biology

Iron is critical for the growth and survival of almost all cells in living organisms. Due to its ability to function as a co-factor for a wide range of proteins, iron plays a key role in cell growth, replication, and metabolism in the human body. However, excess accumulation of free iron can induce reactive oxygen species (ROS) via the Fenton reaction causing significant cellular damage, which could precipitate various pathologies including carcinogenesis. Therefore, patients suffering from diseases that associate with significant iron overload, such as hemochromatosis, are at high risk of developing various forms of cancer including those of the breast, lung, colon, prostate, rectum as well as hepatocellular carcinoma.

Our research endeavors are directed towards investigating specific genes that undergo activation or suppression due to environmental influences, thereby contributing to the development of Breast, Gastric, Liver and Colorectal cancers. Up to this point, we have successfully identified numerous epigenetic markers, particularly associated with genes responsible for regulating iron levels within our cellular structures. These genes play a pivotal role in the initiation of these cancer types. 

We have found that some environmental factors over time are disturbing the iron regulation process in our liver and intestinal cells, hence pushing them towards abnormal growth leading to cancer formation. Using this knowledge, we are now working towards targeting those epigenetic changes to make the cancer cells more sensitive towards the usual chemotherapy treatment; hence, making it much easier, and with fewer side effects to treat cancer patients. Moreover, as those epigenetic changes happen at very early stages of cancer development, we can use them to diagnose patients at high risk of cancer and start the treatment well before they reach the advanced stage.

Goals:

Understand the role of iron metabolism in complex diseases such as cancer and diabetes in the hope of identifying biomarkers and pathways that can be of theranostic value. Our dynamic group focuses on the following objectives by combining animal models with high-throughput transcriptomic/proteomics approaches, bioinformatics tools, and clinical sample analyses.

Objectives:

• To study estrogen-dependent epigenetic re-programming in liver and breast cancers

• To investigate the role of ferritin in cancer growth, metastasis, and treatment

• To study the anti-cancer effects of metformin as an iron metabolism disruptor

• To investigate the role of iron-metabolism genes in cancer growth, and metastasis

• To examine the anti-cancer drug candidates that might disrupt iron metabolism

• To study iron metabolism-related genes in immunological disorders.

1. Iron metabolism in gastrointestinal and liver carcinoma

2. Iron dysregulation in infectious diseases, including COVID-19 and lung diseases

3. Iron metabolism in breast cancer, endometrial, cervical cancers

4. Role of iron in Type 2 diabetes and pancreatic beta cells functions

5. Iron overload or depletion in arthritis, and chondritis and skeletal diseases

Research Grants

1. University of Sharjah competitive grant.  Screening for HLA haplotype and immune function-related gene variants as host-related factors predisposes to cytokine storm syndrome in Emirati COVID-19 patients. Mawieh Hamad PI; Jibran Muhammad. Jalal Taneera Co-PI- total fund awarded: AED 197,000

2. Sharjah Research Academy/University of Sharjah joint research funding program. The anti-apoptotic effects of estrogen-induced intracellular iron efflux in pancreatic β-cells. Mawieh Hamad, PI; Jibran Muhammad. Jalal Taneera, Co-PI - total fund awarded: AED 361,000.

3. University of Sharjah competitive research grant. Investigating the molecular interaction of iron and calcium dysregulation in the cellular phenotype of osteoarthritis. Asima Karim PI; co-PI: Prof. Mawieh Hamad, Dr. Khuloud Bajbouj- Amount: AED 80, 000

4. University of Sharjah competitive research grant. The anti-tumor effects of dendritic cell exosome secretions, Competitive research project. Funded by UOS/VCRGS. "Investigators: - PI: Mohammad G Mohammad (UOS), Abdou Gomaa Abdou Elsharawi (Institute of Clinical Molecular Biology) - total fund awarded: AED 80,000.

5. Al-Jalila Foundation, Dubai, UAE, “Estrogen-induced epigenetic regulation of iron metabolism in hepatocellular carcinoma”, Dr. Jibran (PI), Dr. Khuloud, Dr. Mawieh co-PI - total fund awarded: AED 292,000.

6. University of Sharjah targeted research grant.  Evaluating the interaction of haptoglobin polymorphism with hepcidin and CD163 and their role in iron homeostasis in type 2 diabetes mellitus.  Samir Awadallah PI, M Hamad Co-PI, the total fund awarded: AED 194,000.

7. University of Sharjah competitive grant.  Methylation Silencing of Yes-associated Protein (YAP) Facilitates Carcinogenesis in Breast Adenocarcinoma.  Jibran PI, M Hamad Co-PI, total amount: AED 80,000.

1. Jibran Sualeh Muhammad received Promising Researcher Award 2022 from The King Hussein Award for Cancer Research, Jordan (https://www.kinghusseincanceraward.jo/en/winner/dr-jibran-muhammad)
2. Jibran Sualeh Muhammad received University of Sharjah Annual Faculty Incentive Award 2022-23 (Scientific Research Category)

1. Sharjah Research Academy/University of Sharjah joint research funding program. The anti-apoptotic effects of estrogen-induced intracellular iron efflux in pancreatic β-cells. Mawieh Hamad PI; Jibran Muhammad. Jalal Taneera Co-PIs. Total fund awarded: AED 361,000.
2. University of Sharjah competitive grant.  Screening for HLA haplotype and immune function-related gene variants as host-related factors predisposes to cytokine storm syndrome in Emirati COVID-19 patients. Mawieh Hamad PI; Jibran Muhammad. Jalal Taneera Co-PI. Total fund awarded: AED 197,000.
3. University of Sharjah competitive research grant. Investigating the molecular interaction of iron and calcium dysregulation in the cellular phenotype of osteoarthritis. Asima Karim PI; Prof. Mawieh Hamad, Dr. Khuloud Bajbouj, Co-PIs. Total fund awarded: AED 80,000.
4. King Hussein Cancer Foundation, Jordan. Epigenetic sensitization of liver cancer towards chemotherapeutic drug treatment. Jibran Sualeh Muhammad PI; Mawieh Hamad Co-PI. Total fund awarded: USD 90,000.
5. University of Sharjah competitive research grant. Epigenetic modulation of metabolism in colorectal carcinogenesis. Jibran Sualeh Muhammad PI; Mawieh Hamad Co-PI. Total fund awarded: AED 120,000.