TITLE: "Biophysical Studies of Sickle Cell Hemoglobin"

SPEAKER: Professor Dany Kim-Shapiro,

TIME: Thursday Jan. 25, 2001 at 4 PM

PLACE: George P. Williams, Jr. Lecture Hall, (Olin 101)

Sickle cell disease is caused by a single mutation in one of the genes for hemoglobin, the oxygen carrying molecule contained in red blood cells. The mutant form of hemoglobin, called sickle cell hemoglobin or hemoglobin S (HbS) polymerizes under hypoxic conditions (when there is little or no oxygen present). The polymerization of HbS deforms the red cells which decreases the bulk viscosity of the blood and makes it difficult or impossible for the red cells to enter capillaries in the microvasculature. This often results in blockages in the microvasculature that cause a lot of pain and sometimes death.

Previous biophysical studies have been partially responsible for the development of current treatments of sickle cell disease. We use various forms of biospectroscopy such as light scattering, absorption, diffraction, and electron paramagnetic resonance to study various aspects of the disease. In some cases we are developing new tools to better study HbS and other biological macromolecules. Our goal is to gain a better understanding of the basic science related to HbS and other macromolecules and thereby open new avenues for therapy.

I will present an overview of several of the projects we have been working on. We have been studying the rate of unsickling of red cells when they are oxygenated at the lungs. We have also been exploring the mechanism by which an FDA approved drug, Hydroxyurea, benefits patients. Finally, we have begun studies of nitric oxide and its interactions with hemoglobin in the blood since clinical trials on nitric oxide inhalation therapy have begun for patients with sickle cell disease.