Welcome to Donna's Homepage

I am in my final year of graduate studies in the physics department at Drexel University. I received my M.S. in Physics from Drexel in 2007. Just select a tab above to learn more about my research or click a link below to see a few of the classes I have taught.

Research Summary:

My area of research is biophysics. Of particular interest to my group is protein aggregation, such as Sickle Hemoglobin, and micro-device development and implementation to study protein aggregates intra and extra-cellular.

Classes taught while at Drexel:

Abstract for Platform Presentation at Sickle Cell Disease Association of America (SCDAA) Meeting 2010 in D.C.

CAN CHANGING P50 ALONE BE AN EFFECTIVE THERAPY FOR SICKLE CELL DISEASE?

Donna Yosmanovich (Presenter) & Frank Ferrone

Because oxygenated sickle hemoglobin will not polymerize, any modifications that retain the oxygenated (R) structure of the hemoglobin ought, and in fact have been observed, to inhibit the sickling process whenever deoxygenation is incomplete. It is unclear to what extent this observation made in the laboratory can translate to clinical applications, given the likelihood that homeostasis will return the net p50 to its original value. Accordingly we undertook a series of computational studies to determine how changed p50 of one component of blood would affect sickle hemoglobin polymerization in the presence of homeostasis of the entire organism. Our calculations are based on two extensively tested and highly robust models that guide our understanding of hemoglobin oxygen binding and polymerization. For kinetics of polymerization, we employed the double nucleation model, which describes polymerization as due to a homogeneous pathway that initiates polymerization and a heterogeneous pathway that nucleates new polymers on the surface of others. Essential to this application of the model is the inclusion of partially liganded species. Theoretical and experimental developments support the idea that such species can be accurately included in the model. For the computation of the concentration of partially oxygenated species we employ a simple MWC allosteric model which has been extensively used to correlate hemoglobin oxygen binding with structure change. This model considers hemoglobin to assume two quaternary structures, R and T, between which the molecule switches during binding of ligands. This model is related to sickling because the R structure is incapable of polymerization, and the T structure polymerizes with a likelihood that diminishes as more ligands are added.

Abstract for Poster Presented at Biophysical Society Meeting 2009 in Boston

Ligand Binding and Sickle Hemoglobin Polymerization Kinetics: Implication for Therapies

Donna Yosmanovich, Maria Rotter, Alexy Aprelev, Frank Ferrone

Sickle Cell Disease results from a point mutation on the beta subgroups of hemoglobin. When hemoglobin releases its four ligands it changes from a relaxed (R) structure to a tense (T) structure and the mutation causes polymer chains to grow. Typical in vitro experiments measure this through complete photolysis of a COHbS sample with a laser and then quantify the scattered light from growing polymers. However, in vivo, many molecules are partially liganded due to the incomplete transfer of oxygen from red blood cells to the surrounding tissue. Liganded T state molecules could contribute to polymer growth, although until now the effect on the kinetics of fractional saturation was unknown. We examined the effects of introducing NO into COHbS samples. The strong binding of NO to HbS keeps the ligand distribution unchanged during the COHbS experiment. We found that the NOHbS caused the polymerization rate to decrease by 50% due to tertiary inhibition of the partially bound T state hemoglobin. We ruled out the possible effects of non-polymerizing R state NO Hb through a flash photolysis experiment, where photolysis curves were analyzed for an initial fast recombination to R state Hb. Only an insignificant possible amount of R state was found (<3%), and could not account for the effects recorded. The effect of partial ligation on polymerization is important in analyzing possible therapies for sickle cell disease. One possible therapy would be to alter the oxygen affinity of Hb, thereby decreasing the number of fractional intermediates and decreasing the number of T state HbS overall.