Sickle cell disease (SCD) is an inherited gene defect that causes hemoglobin to clump and deform red blood cells, leading to anemia, hemolysis, and vascular occlusions that affect multiple organs. Moreover, sickle shaped red blood cells stick to blood vessel walls thereby slowing or stopping blood flow and the cells lining the blood vessel walls can abnormally express adhesion molecules or proteins that trigger blood coagulation and inflammation in this patients. Dr. Shet’s research aims to better understand the different factors initiating and propagating venous thrombosis in sickle cell disease. To achieve this, in vitro coagulation assays, flow cytometry, and biochemical assays, as well as animal studies (predominantly murine models of SCD) are used to study the mechanisms of coagulation activation and inflammation in SCD. The laboratory also performs translational research exploring the effect of investigational drugs as modifiers of thrombotic risk in SCD patients and SCD mice.
Arun Shet, MD, PhD, is an assistant clinical investigator who leads the Laboratory of Sickle Thrombosis and Vascular Biology at the NHLBI.
- Shet AS, Lizarralde-Iragorri MA, Naik RP. The molecular basis for the prothrombotic state in sickle cell disease. Haematologica. 2020;105(10):2368-2379.
- Tumburu L, Ghosh-Choudhary S, Seifuddin FT, Barbu EA, Yang S, Ahmad MM, Wilkins LHW, Tunc I, Sivakumar I, Nichols JS, Dagur PK, Yang S, Almeida LEF, Quezado ZMN, Combs CA, Lindberg E, Bleck CKE, Zhu J, Shet AS, Chung JH, Pirooznia M, Thein SL. Circulating mitochondrial DNA is a proinflammatory DAMP in sickle cell disease. Blood. 2021;137(22):3116-3126.
- Strader MB, Jana S, Meng F, Heaven MR, Shet AS, Thein SL, Alayash AI. Post-translational modification as a response to cellular stress induced by hemoglobin oxidation in sickle cell disease. Sci Rep. 2020;10(1):14218.
- Shet AS, Mendelsohn L, Harper J, Ostrowski D, Henry ER, Gwaabe E, Nichols J, Alayash AI, Eaton WA, Thein SL. Voxelotor treatment of a patient with sickle cell disease and very severe anemia. Am J Hematol. 2019;94(4):E88-E90.
- Vogel S, Arora T, Wang X, Mendelsohn L, Nichols J, Allen D, Shet AS, Combs CA, Quezado ZMN, Thein SL. The platelet NLRP3 inflammasome is upregulated in sickle cell disease via HMGB1/TLR4 and Bruton tyrosine kinase. Blood Adv. 2018;2(20):2672-2680.
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Molecular Biology and Biochemistry
Genetics and Genomics
This page was last updated on Tuesday, September 12, 2023