Joseph E. Kaserman's research while affiliated with Boston University and other places

... ZINC000034518176, ZINC000095485942, NANPDB2933, ZINC000014089759, ZINC000085545967, ZINC000014089743, and ZINC000101564200 were also predicted to be hepatoprotectants with Pa values of 0.926, 0.377, 0.282, 0.929, 0.429, 0.932, and 0.317 and Pi values of 0.002, 0.036, 0.066, 0.002, 0.027, 0.002, and 0.054, respectively. Liver damage is one of the hallmarks of EVD infection [103][104][105]. These compounds may be beneficial with respect to managing liver failure and may support the liver during recovery from EVD. ...

... Recently, researchers engineered PiZZ pluripotent stem cell-derived hepatocytes (iHeps) [35], which recapitulated previously reported endoplasmic reticulum stress and mi-tochondrial dysfunction, among other defects in transcriptomic and metabolomic pathways. Specifically, urea cycle metabolites were found significantly altered in PiZZ iHeps, which was associated with downregulation of urea cycle enzymes (ASS1, CPS1, OTC, ASL), which supports previous observations in PiZ mice regarding ureagenesis impairment [36]. ...

... The inactivation of EBOV-containing samples is strictly regulated in that all inactivation procedures must be validated prior to approval. For this study, we used recombinant EBOV (Mayinga isolate) expressing ZsGreen (EBOV-ZsG) [13]. EBOV-ZsG grows to high viral titers, as needed for this study, and can be easily visualized because cells infected with EBOV-ZsGreen fluoresce green. ...

... but the infection might not lead to disease, similar to the non-pathogenic Reston virus 21 . ...

... 3,20 To complement existing models, we and others have applied ZZ patient-specific induced pluripotent stem cell (iPSC)-derived hepatocytes (iHeps) to recapitulate cellular features of ZAAT-associated liver disease pathogenesis. 1,[21][22][23][24][25] Here, we extend this work to directly test the impact of ZAAT heterozygosity on hepatocyte biology using genetically controlled syngeneic MZ and MM iHeps generated from three distinct ZZ patient-specific iPSC lines. Through a combination of bulk and single-cell RNA sequencing and metabolomics analysis, we find that MZ iHeps exhibit an intermediate phenotype and share with ZZ iHeps significant alterations in AAT protein processing associated with downstream metabolic dysregulation and branch-specific activation of the unfolded protein response (UPR) among cellular subsets. ...

... 3,20 To complement existing models, we and others have applied ZZ patient-specific induced pluripotent stem cell (iPSC)-derived hepatocytes (iHeps) to recapitulate cellular features of ZAAT-associated liver disease pathogenesis. 1,[21][22][23][24][25] Here, we extend this work to directly test the impact of ZAAT heterozygosity on hepatocyte biology using genetically controlled syngeneic MZ and MM iHeps generated from three distinct ZZ patient-specific iPSC lines. Through a combination of bulk and single-cell RNA sequencing and metabolomics analysis, we find that MZ iHeps exhibit an intermediate phenotype and share with ZZ iHeps significant alterations in AAT protein processing associated with downstream metabolic dysregulation and branch-specific activation of the unfolded protein response (UPR) among cellular subsets. ...

... Hepatocytic Alpha-1-antitrypsin deficiency ZAAT polymer accumulation (Choi et al. 2013;Kaserman and Wilson 2018;Tafaleng et al. 2015) Alpers syndrome Reduced optic atrophy 1 protein (Li et al. 2015) Citrin deficiency Impaired ureagenesis (Kim et al. 2016) Hemophilia A FVm deficiency (Jia et al. 2014;Olgasi et al. 2018) Infantile-onset Pompe disease Lysosomal glycogen accumulation (Yoshida et al. 2019) Liver fibrosis (iPSC-HSC) Retinyl esters accumulation (Coll et al. 2018) Niemann-pick disease type C Cholesterol accumulation (Soga et al. 2015) Tangier disease Impaired cholesterol efflux (Bi et al. 2017) Wilson's disease Rapid ATP7B degradation (Parisi et al. 2018;Yi et al. 2012) Biliary Alagille syndrome Organoid malformation (Sampaziotis et al. 2015) Biliary atresia Increased fibrosis Reduced biliary differentiation (Tian et al. 2019) Cystic fibrosis Impaired Cl − channel activity (Simsek et al. 2016) Polycystic liver disease Cholangiocytic cysts (Kamiya et al. 2018) Adv Exp Med Biol. Author manuscript; available in PMC 2022 July 21. ...

... Individuals carrying the Pi*Z variant may retain polymerized A1AT protein within their hepatocytes which leads to varying degrees of reduced serum concentrations of A1AT [9]. Homozygous carriers of the Pi*Z variant ("Pi*ZZ" genotype) may develop progressive liver disease [10][11][12][13][14][15]. Recently, a multinational cohort study revealed that heterozygous carriage of the Pi*Z variant ("Pi*MZ" genotype) is a strong disease modifier in metabolic liver disease (i.e., alcoholic and non-alcoholic fatty liver disease) [16][17][18]. ...

... BU3 was confirmed as mycoplasma free by PCR analysis of gDNA using the following mycoplasma specific primers: 5 0 CTT CWT CGA CTT YCA GAC CCA AGG CAT 3 0 and 5 0 ACA CCA TGG GAG YTG GTA AT 3' and verified as karyotypically normal as determined by Gband karyotyping analysis from 20 metaphases. iPSC directed differentiation towards the hepatic lineage was performed using a previously published protocol [18,39,40]. Briefly, undifferentiated iPSCs were cultured until confluent and then passaged on Day 0 using gentle cell dissociation reagent (GCDR, StemCell Technologies) to achieve single cell suspensions and replated at 1x10 6 cells per well of a Matrigel coated 6-well plate. ...