September 17, 2012 – (BRONX, NY) – The National Heart, Lung, and Blood Institute, part of the National Institutes of Health, has awarded nearly $11 million to Albert Einstein College of Medicine of Yeshiva University to carry out a five-year multi-institutional study of hemoglobin toxicity that may complicate blood transfusions and reduce the effectiveness of blood substitutes. The long-term goals include making blood transfusions safer and more effective and better matching patients with the transfusion strategy best suited to them.
Joel Friedman, M.D., Ph.D.The research is especially important due to the explosion of obesity, diabetes and metabolic syndrome, which increases inflammation in blood vessels and can lead to transfusion complications.
The $10.8 million program project grant will be overseen by the principle investigator, Einstein's Joel Friedman, M.D., Ph.D., who holds the Young Men's Division Chair in Physiology and is professor of physiology & biophysics and of medicine. The grant will fund research projects at Einstein, Rice University, the University of California, San Diego and the United States Food and Drug Administration (FDA), directed by Dr. Friedman, John Olson, Ph.D., Marcos Intaglietta, Ph.D., and Abdu Alayash, Ph.D., respectively.
The grant focuses on the study of hemoglobin, the protein that gives red blood cells their color. Red cells transport oxygen throughout the body and deliver it to cells. Hemoglobin normally stays inside red blood cells. But under some conditions—including sickle cell anemia and transfusions involving stored blood—red cells break open, or lyse, causing substantial amounts of hemoglobin to become acellular (i.e., still in the bloodstream but no longer inside red cells).
Acellular hemoglobin can initiate toxic chemical reactions and processes. This toxicity can trigger or worsen potentially serious inflammation of blood vessels that can complicate blood transfusions and has hampered development of blood substitutes.
The researchers will use the federal grant to determine the mechanisms responsible for making acellular hemoglobin toxic and to develop strategies for preventing, reducing or even reversing toxicity.
Dr. Friedman has brought together teams from Einstein, Rice, UC San Diego and the FDA to take different but complementary research approaches. Dr. Friedman and his Einstein colleagues, including Parimala Nacharaju, Ph.D., instructor in physiology & biophysics, will study several possible strategies for neutralizing acellular hemoglobin toxicity, including the novel use of nanoparticles that release nitric oxide gas. These particles were developed at Einstein to counteract the role played by acellular hemoglobin in reducing nitric oxide levels.
The Rice/FDA team will evaluate strategies for limiting the toxic consequences of acellular hemoglobin, which include hypertension caused by reduced nitric oxide levels and damage to blood vessel walls caused by harmful chemicals called free radicals. The UC San Diego team, which includes Amy Tsai, Ph.D., and Pedro Cabrales, Ph.D., will conduct animal testing to discover the mechanisms responsible for hemoglobin-based toxicities and develop ways to reduce or eliminate them.