Graduate Program, Pathobiology & Molecular Medicine

Robert S. Franco, Ph.D.
•• Int Med-Hemat/Oncology
•• Research Professor
•• e-mail

University of Cincinnati, PhD, 1971

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.

Recent Publications

1. Joiner CH, Jiang M, Claussen WJ, Roszell NJ, Yasin Z, and Franco RS. Dipyridamole inhibits sickling-induced cation fluxes in sickle red blood cells. Blood 97:3976-3983, 2001.

2. Franco RS, Yasin Z, Lohmann JM, Palascak M, Nemeth TA, Weiner M, Joiner CH, and Rucknagel DL: The survival characteristics of dense sickle cells. Blood 96: 3610-3617, 2000.

3. A.J. McGoron, C.H. Joiner, M. Palascak, W. Claussen, and R.S. Franco: Dehydration of mature and immature sickle red blood cells during fast oxygenation/deoxygenation cycles: Role Of KCl Cotransport And Extracellular Ca++ . Blood 95:2164-2168,2000.

4. Franco RS, Lohmann J, Silberstein EB, Mayfield-Pratt G, Palascak M, Nemeth TA, Joiner CH, Weiner M, and Rucknagel DL: Time-dependent changes in the density and hemoglobin F content of biotin-labeled sickle cells. J. Clin. Inv. 101:2730-2740,1998.

5. The activationof KCL cotransport by deoxygenation and its role in sickle cell dehydration. Joiner CH: Franco RS Blood Cells, Molecules, and Diseases vol. 27, no. 1 (2001 Jan-Feb): 158-64.