The research conducted in our lab centers on sickle cell disease and its treatment through pharmacologic as well as genetic approaches. Our genetic work has been driven by our participation in the Nanomedicine Center for Nucleoprotein Machines whose focus includes the development of nanomedicine-based strategies for gene correction in hemoglobinopathies such as sickle cell disease. We joined this group of renowned scientists in 2008. We have had some success in this venture and continue to find ways to correct the single-base mutation found in sickle cell disease.
Currently hydroxyurea is the only FDA-approved treatment for SCD. It induces fetal hemoglobin expression and can alleviate the complications associated with the disease. Unfortunately not all patients respond to hydroxyurea and the search continues for effective treatments. In the past investigators have searched for more effective inducers of fetal hemoglobin. More recently we have begun to look for ways to counteract and/or prevent the damage caused by the sickled red blood cells. For example, we are studying the contribution of endothelin-1 in the pathobiology of SCD.
Laird MD, Wakade C, Sangeetha SR, Meiler SE, Vender JR, and Dhandapani KM. Curcumin attenuates cerebral edema following traumatic brain injury in mice via a reduction in aquaporin-4. J Neurochem. 1;113(3):637-48, 2010.
Kutlar F, Redding-Lallinger R, Meiler SE, Bakanay SM, Borders L, Kutlar A. A new sickling variant 'Hb S-Wake β[(Glu6Val-Asn139 Ser)]' found in a compound heterozygote with Hb S β(Glu6Val) coinherited with homozygous α-thalassemia-2: phenotype and molecular characteristics. Acta Haematol.124(2):120-4, 2010.
King MD, McCracken DJ, Wade FM, Meiler SE, Alleyne CH, Dhandapani KM. Attenuation of hematoma size and neurological injury with curcumin following intracerebral hemorrhage in mice. J Neurosurg. 115(1):116-23, 2011.
Meiler SE, Wade M, Kutlar F, Yerigenahally SD, Xue Y, Moutouh-de Parseval LA, Corral LG, Swerdlow PS, Kutlar A. Pomalidomide augments fetal hemoglobin production without the myelosuppressive effects of hydroxyurea in transgenic sickle cell mice. Blood. 118(4):1109-12, 2011.
dos Santos JL, Lanaro C, Lima LM, Gambero S, Franco-Penteado CF, Alexandre-Moreira MS, Wade M, Yerigenahally S, Kutlar A, Meiler SE, Costa FF, Chung M. Design, synthesis, and pharmacological evaluation of novel hybrid compounds to treat sickle cell disease symptoms. J Med Chem. 54(16):5811-9, 2011.
Sabio H, Dixon N, Patel N, Obiaga C, Zhuang L, Meiler SE, Kutlar A, Kutlar F. Thalassemia-like phenotype in a novel complex hemoglobinopathy with α, β, δ globin chain abnormalities. J Pediatr Hematol Oncol. 33(8):589-91, 2011.
Chen Z, Jaafar L, Xiao H, Agyekum D, Wade M, Kumaran RI, Spector DL, Bao G, Matthew H. Porteus MH, Dynan WS, Meiler SE. Receptor-mediated delivery of engineered nucleases for genome modification. Nucl Acids Res. 41(19):e182, 2013.
Meiler S (Co-PI). The Role of Endothelin-1 in Sickle Cell Disease. NIH/National Heart, Lung, and Blood Institute, 2014-2019
Location of Lab: CB-3915, 706-721-7895