Isabel Mérida leads one of the four projects selected this year for funding by the Aplastic Anemia and MDS International Foundation

The Aplastic Anemia and MDS International Foundation (AAMDSIF) has awarded Isabel Merida's study on the role of diacylglycerol kinase zeta in early stages of aplastic anemia with a two-year grant.

AAMDSIF is the world's leading nonprofit health organization dedicated to patients afflicted with bone marrow failure disease. For nearly 30 years, AAMDSIF has provided research grants totaling in excess of $4 million to an international group of more than 75 researchers to help advance the understanding and treatment of aplastic anemia, myelodysplastic syndromes (MDS), and paroxysmal nocturnal hemoglobinuria (PNH).


Aplastic anemia is a disease in which the bone marrow gradually stops producing red and white blood cells and platelets. As a result, people with aplastic anemia feel tired, may bleed more easily and are at higher risk of having infections. Aplastic anemia can strike at any age but is more often diagnosed in children, young adults and older people. In a few cases aplastic anemia is passed from parents to their child, but most often this disease results from destruction of the cells in the bone marrow by overactive immune system blood cells called T-cells. Healthy T cells are "trained" to recognize and destroy exclusively foreign invaders of the body, such as viruses. But in some cases, T cells attack the cells from the body, causing autoimmune diseases like lupus or rheumatoid arthritis.

Patients with aplastic anemia are treated with multiple medicines to suppress the autoimmune response that damages their bone marrow. In addition, they must receive frequent blood transfusions as well as other drugs to fight infections. The only cure is a bone marrow transplant, which is very costly and require the identification of full or at least half-matched donors. Today, nobody knows the exact cause by which T cells suddenly attack the cells in the bone marrow. For this reason, it is very important to investigate and learn more about the reasons that lead T cells to destroy healthy cells.

Isabel Merida's research group has specialized for many years in the study of the mechanism that help T cells to recognize the cells in the body to avoid their destruction. Some years ago, they contributed to describe that Diacylglycerol kinase z (DGKz), a protein expressed in T lymphocytes, functions as a brake limiting immune-dependent T cell attack. They recently found that when mice are genetically modified to suppress DGKz expression, they have increased numbers of activated T lymphocytes in their bone marrow. They also show signals of bone marrow destruction suggesting that DGKz could be important to limit the activation of T lymphocytes in the bone marrow.

Isabel Mérida was thrilled by learning that other investigators had found that the T lymphocytes of aplastic anemia patients showed reduced expression of DGKz. Those patients with very severe symptoms also showed the more reduced expression of this T cell brake. Her group is now investigating the reasons by which T lymphocytes with reduced DGKz expression enter and destroy the cells in the bone marrow. They also want to explore whether mice with no DGKz develop more severe symptoms of the disease when exposed to known causes of aplastic anemia like radiation. These studies may be helpful to understand better the causes that trigger aplastic anemia and identify proteins, like DGKz, as indicators of the severity of the disease.

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