RBC-Omics and GWAS

NHLBI's Recipient Epidemiology Donor Evaluation Study (REDS)-III RBC-Omics study was designed to define genetic and metabolomic bases for donor-specific differences in RBC storage stability. The RBC-omics' cohort included 13,403 blood donors. Among the tested end points, predisposition to osmotic hemolysis was highly reproducible in repeated donations and subsequent genome-wide association studies have identified multiple genes, for which single nucleotide polymorphisms (SNPs) altered hemolytic response to osmotic stress.

I am specifically interested in mutations that impact members of the mitogen-activated protein kinase (MAPK) protein family, which were originally identified in comparable GWA studies of hemolysis in mice during my tenure at the University of Pittsburgh. Our overarching goal is to verify the impact of selected SNPs on RBC survival in vitro and in vivo using biotinylated RBCs.

Selected Publications:

Kanias T, Lanteri M, Grier P, Yuelong J, Endres S, Stone M, Keating S, Mast A, Cable R, Triulzi D, Kiss J, Murphy E, Kleinman SH, Busch MP, Gladwin MT. Ethnicity, sex and age are determinants of red blood cell storage and str

Kanias T, Stone M, Page GP, Guo Y, Endres-Dighe SM, Lanteri MC, Spencer BR, Cable RG, Triulzi DJ, Kiss JE, Murphy EL, Kleinman SH, Gladwin MT, Mast AE, Busch MP. Frequent blood donations alter susceptibility of red blood cells to storage- and stress-induced hemolysis. Transfusion 2018: Accepted Manuscript- In Press.

Endres-Dighe SM, Guo Y, Kanias T, Lanteri MC, Stone M, Spencer BR, Cable RG, Kiss JE, Kleinman SH, Gladwin MT, Brambilla DJ, D'Andrea P, Triulzi DJ, Mast AE, Page GP, Busch MP. Blood, Sweat and Tears: Red Blood Cell-Omics Study Objectives, Design, and Recruitment Activities. Transfusion 2018: Accepted Manuscript- In Press.

Guo Y, Busch MP, Seieistad M, Endres-Dighe SM, Westhoff CM, Keating B, Hoope C, Bordar A, Custer B, Butterworth AS, Kanias T, Mast AE, Kleinman SH, Lu Y, Page GP. Development and evaluation of a transfusion medicine genome wide genotyping array. Transfusion 2018: Accepted Manuscript- In Press.

Saraf SL, Zhang X, Shah B, Kanias T, Gudehithlu KP, Kittles R, Machado RF, Arruda J, Gladwin MT, Singh AK, Gordeuk VR. Genetic Variants and Cell-Free Hemoglobin Processing in Sickle Cell Nephropathy. Haematologica 2015. 100: 1275-84.