Hematologic & Oncogenic Disease

Robert Franco

Robert Franco, PhD

Int Med-Hemat/Oncology

Research Professor

Research Summary

Homozygous sickle cell disease, which afflicts one in four hundred African-Americans, has been well-described at the gene level. Nevertheless, due to complex genetic and cellular cofactors, the pathophysiology of this disorder is not well understood. Sickle hemoglobin (HbS) polymerizes under low oxygen conditions, distorting the red cell and causing the characteristic sickled morphology. These rigid and misshapen cells have a short survival in the circulation and cause acute vascular occlusion and chronic organ damage. HbS polymerization is highly dependent upon the concentration and composition of hemoglobin, which in turn are determined by the hydration state of the cell and the presence or absence of the fetal form of hemoglobin, HbF. Cells that contain HbF are highly resistant to sickling, and drugs that increase HbF are currently being evaluated.

The laboratory of Robert S. Franco, Ph.D., located in the Hematology/Oncology Division of the Department of Internal Medicine, has developed novel approaches to characterize sickle cells by age, hydration status, and hemoglobin composition. For each defined cell type, the activity of the cation transporters which determine hydration state are evaluated in the unstimulated state and also in the presence of various activating conditions, including cyclical deoxygenation. In this way, a new mechanistic model of sickle cell dehydration and survival has been developed. For detailed studies of time-dependent in vivo cellular changes, sickle cells are labeled with biotin and reinfused. The biotinylated cells are identified in subsequent blood samples by a sensitive flow cytometric technique, allowing measurement of a number of time-dependent changes, including hydration state.

Dr. Franco has published over 50 manuscripts. He is a member of the American Association for the Advancement of Science, American Society of Hematology, and the American Association of Blood Banks. He remains active on several committees at UC, including the Program Committee for the Pathobiology and Molecular Medicine Graduate Program (Responsible for all aspects of the graduate program); Department of Internal Medicine Research Committee (Oversees research initiatives, seminar series, and graduate education); College of Medicine Post-doctoral Scholars Advisory Committee (Formulates policy and organizes events related to postdoctoral education); and the Comprehensive Sickle Cell Center Research Committee (Reviews current studies and plans future research for the Sickle Cell Center.)

Recent Publications

Latorya A. Barber, Mary B. Palascak, Clinton H. Joiner, and Robert S. Franco.Aminophospholipid Translocase and Phospholipid Scramblase Activities in Sickle Erythrocyte Subpopulations.Accepted for publication, Br J Haematology.

Ajay Perumbeti, Tomoyasu Higashimoto, Fabrizia Urbinati, Robert Franco, Herbert Meiselman, David Witte, and Punam Malik.Genetic Correction of Sickle Cell Anemia with a Gamma-Globin Expressing Lentivirus Vector and Critical Determinants for Successful Correction.Submitted for Publication.

Franco, Robert S.: The measurement and Importance of Red Cell Survival (Invited Review).Am J Hematol 84:109-114,2009.

Haiyan Chu, Andrew Breite, Peter Ciraolo, Robert S. Franco, and Philip S. Low.Characterization of the deoxyhemoglobin binding site on human erythrocyte band 3: implications for O2 regulation of erythrocyte properties.Blood 111:932-938,2008.

Khera PK, Joiner CH, Carruthers A, Lindsell CJ, Franco RS, Holmes YR, Smith EP, Cohen RM.Evidence for Inter-Individual Variation in the Glucose Gradient Across the Human RBC Membrane and Its Relationship to HbA1c.Diabetes 57:2445-2452,2008.

 

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