QCBR scientists have been awarded major research grants from the National Institutes of Health (NIH), which have been put to good use by generating over 80 peer-reviewed publications and invited review articles since 1998, 25% of which appeared in the best biomedical research journals of the world, honoring The Queen’s Medical Center and Hawaii. QCBR’s newest line of inquiry focuses on the translation of its most important findings on the molecular level into therapeutic options for Queen’s patients and all patients alike through a drug-screening effort against diabetes, cardiovascular disease, immune disease and cancer.
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Restrictions in blood flow can lead to a reduction of much-needed oxygen supply in the tissue affected. This is particularly damaging to organs that have large oxygen consumption needs, such as the brain. Absence of adequate supply of oxygen in the brain ultimately leads to the death of nerve cells. The laboratory of Dr. Fleig and collaborators discovered a new protein called TRPM7. This research was published in the journal Nature in 2001. The function of the TRPM7 protein depends on adequate supply of oxygen and sugar in the blood stream to maintain brain and other tissue cells alive and functioning normal. Using animal models it has been demostrated that suppressing TRPM7 function protects brain cells from dying after a heart attack, supporting the hypothesis that the activity of TRPM7 may play a central role during stroke as well.
The Weinman Award, an annual grant of $50,000, is directed to support innovative translational research with the potential to develop new diagnostic or therapeutic approaches to cancer. Andrea Fleig and colleagues first discovered the molecular nature and the physiological function of the ion channel named TRPM7 and demonstrated its central role for cell growth and proliferation. Ion channels act like tiny gates and pores in the cell’s membrane, allowing entry or exit of vital molecules, in this case the divalent ion magnesium. Magnesium is essential for cells to divide and proliferate, and this is particularly so for cancer cells.
While screening marine-derived natural products to interfere with the normal function of the TRPM7 channel, Fleig and colleagues identified a natural compound isolated from a Hawaiian soft coral, which acts to stop multiplication of cancer cells by interfering with the magnesium status of these cells. The translational project aims to stop the development of colon cancer in a mouse model exploiting this mechanism.
Around 200–400 million people in South and Southeast Asia and the Asian Pacific Region, including Guam, and about 600 million worldwide consume Areca (betel) nuts. The International Agency for Research on Cancer (IARC) regards the chewing of betel and areca nut to be a known human carcinogen. Regular chewers of betel leaf and areca nut have a higher risk of damaging their gums and acquiring cancer of the mouth, pharynx, esophagus and stomach. Dr. Penner’s laboratory is looking to find which ingredients of Areca nut are harmful to humans.
A century-old drug that has worked well as an anti-leprosy medicine shows new promise as a potential therapy for multiple sclerosis and other autoimmune diseases. In a multi-institutional collaboration between researchers at QCBR, John’s Hopkins, and Northwestern University, a new mechanism was uncovered for the anti-leprosy drug clofazimine. It was found that clofazimine could shut down certain potassium channels in immune cells, thereby dampening immune responses.
Because clofazimine is known to be safe, further tests that prove its effectiveness in treating multiple sclerosis, rheumatoid arthritis, psoriasis and other autoimmune disorders could lead to quick approval for clinical use against these conditions. This is a current field of research in Dr. Penner’s laboratory. Eventually, clofazimine could also proof beneficial for reducing the risk of skin and organ transplant rejection.