Regulation of protein function and gene expresssion by post-translational modification. Biochemistry of protein damage, aging, and repair. Biochemical characterization of protein pharmaceuticals.
NIH Research Career Development Award.
Editorial Board, The Journal of Biological Chemistry
1974-1977: UCLA, Biology Dept., with Prof Roger Eckert. Neurobiology.
1977-1980: Yale University School of Medicine, Dept. of Pharmacology, with Prof. Paul Greengard (Nobel Laureate, 2000). Neurobiology & Biochemistry.
Post-translational modification serves as an important mechanism for modulating the structure, activity and lifetime of many proteins. My laboratory is exploring the cellular function of protein L-isoaspartyl methyltransferase (PIMT), an enzyme that methylates damaged proteins that contain atypical isoaspartyl residues. Substantial evidence indicates that this enzyme serves to repair these atypical residues by converting the isopeptide bond to a normal peptide bond. Current research is focused on determining the effect of rare polymorphisms on the activity and stability of recombinant human PIMT.
PLEASE NOTE: PROF. ASWAD RECENTLY RETIRED AND IS NO LONGER CONSIDERING APPLICATIONS FOR RESEARCH POSITIONS IN HIS LABORATORY.
Kim J, Chen B, Bru JL, Huynh E, Momen M, and Aswad DW. (2018) New findings on SNP variants of human protein L-isoaspartyl methyltransferase that affect catalytic activity, thermal stability, and aggregation. PLoS ONE 13(6):e0198266. PMID: 29856810
Juang C, Chen B, Bru JL, Nguyen K, Huynh E, Momen M, Kim J, Aswad DW. (2017) Polymorphic Variants of Human Protein L-Isoaspartyl Methyltransferase Affect Catalytic Activity, Aggregation, and Thermal Stability; Implications for the Etiology of Neurological Disorders and Cognitive Aging. J Biol Chem. 292:3656-3665. PMID: 28100787
Pulido MA, DerHartunian MK, Qin Z, Chung EM, Kang DS, Woodham AW, Tsou JA, Klooster R, Akbari O, Wang L, Kast WM, Liu SV, Verschuuren JJ, Aswad DW, Laird-Offringa IA. (2016) Isoaspartylation appears to trigger small cell lung cancer-associated autoimmunity against neuronal protein ELAVL4. J Neuroimmunol. 299:70-78. PMID: 27725125
Qin Z, Zhu JX, Aswad DW. (2016) The D-isoAsp-25 variant of histone H2B is highly enriched in active chromatin: potential role in the regulation of gene expression? Amino Acids 48(2):599-603. PMID: 26666674.
Cahill L, Aswad DW. (2015) Sex Influences on the Brain: An Issue Whose Time has Come. Neuron 88(6):1084–1085.
Qin Z, Dimitrijevic A, and Aswad DW (2015) Accelerated protein damage in brains of PIMT+/- mice; a possible model for the variability of cognitive decline in human aging. Neurobiology of Aging, 36:1029-36 PMID:25465735
Dimitrijevic A, Qin Z, Aswad DW. (2014) Isoaspartyl formation in creatine kinase B is associated with loss of enzymatic activity; implications for the linkage of isoaspartate accumulation and neurological dysfunction in the PIMT knockout mouse. PLoS One. 9(6):e100622.23. PMID:24955845
Qin Z, Yang J, Klassen HJ, and Aswad DW (2014) Isoaspartyl Protein Damage and Repair in Mouse Retina. Invest Ophthalmol Vis Sci. 55:1572-1579. PIMD:24550364
Doyle HA, Aswad DW, and Mamula MJ. (2013) Autoimmunity to isomerized histone H2B in systemic lupus erythematosus. Autoimmunity 46, 6-13. PMID: 22967069
Qin Z, Kaufman RS, Khoury RN, Khoury MK, and Aswad DW (2013) Isoaspartate accumulation in mouse brain is associated with altered patterns of protein phosphorylation and acetylation, some of which are highly sex-dependent. PLoS One 8(11):e80758. PMID: 24224061
Morrison GJ, Ganesan R, Qin Z, and Aswad DW. (2012) Considerations in the identification of endogenous substrates for protein L-isoaspartyl methyltransferase: the case of synuclein. PLoS One 7(8):e43288. PMID: 22905247.
Khoury MK, Parker I and Aswad DW (2010) Aquisition of chemiluminescent signals from immunoblots with a digital SLR camera. Analyt. Biochem. 397, 129-31.
Carter WG and Aswad DW (2008) Formation, localization, and repair of L-isoaspartyl sites in histones H2A and H2B in nucleosomes from rat liver and chicken erythrocytes. Biochemistry 47, 10757-64.
Zhu, JX and Aswad, DW (2007) Selective cleavage of isoaspartyl peptide bonds by hydroxylamine after methyltransferase priming. Analyt. Biochem. 364, 1-7.
Zhu JX, Doyle HA, Mamula MJ, Aswad DW. (2006) Protein repair in the brain: proteomic analysis of endogenous substrates for protein L-isoaspartyl methyltransferase in mouse brain. J Biol Chem. 281,33802-13.
Young, A.L., Carter, W.G., Doyle, H.A., Mamula, M.J. and Aswad, D.W. (2001) Structural integrity of histone H2B in vivo requires the activity of protein L-isoaspartyl methyltransferase, a putative protein repair enzyme. J. Biol. Chem. 276, 37161-37165.
Reissner KJ, Paranandi MV, Luc TM, Doyle HA, Mamula MJ, Lowenson JD, and Aswad DW (2006) Synapsin I is a major endogenous substrate for protein L-isoaspartyl methyltransferase in mammalian brain. J. Biol. Chem. 281, 8389-98.
Yang ML, Doyle HA, Gee RJ, Lowenson JD, Clarke S, Lawson BR, Aswad DW, Mamula MJ. (2006) Intracellular protein modification associated with altered T cell functions in autoimmunity. J Immunol. 177, 4541-9.
Young, G.W, Hoofring, S.A., Mamula, M.J., Doyle, H.A., Bunick, G.J., Hu, Y. and Aswad, D.W (2005) Protein L-isoaspartyl methyltransferase catalyzes in vivo racemization of aspartate-25 in mammalian histone H2B. J. Biol. Chem. 280, 26094-98.
Reissner, K. J. and Aswad, D.W. (2003) Deamidation and isoaspartate formation in proteins: unwanted alterations or surreptitious signals? Cell. Molec. Life Sci. 60, 1281-95.
Li, H., Park, S., Kilburn, B., Jelinek, M. A., Henschen-Edman, A., Aswad, D. W., Stallcup, M. R. and Laird-Offringa, I. A. (2002) Lipopolysaccharide-induced methylation of HuR, an mRNA-stabilizing protein, by CARM1. J. Biol. Chem. 277, 44623-30.
Schurter, B.T., Koh, S.S., Chen, D., Bunick, G.J., Harp, J.M., Hanson, B.L., Henschen-Edman, A., Mackay, D. R., Stallcup, M. R., and Aswad, D.W. (2001) Methylation of histone H3 by coactivator-associated arginine methyltransferase 1. Biochemistry 40, 5747-5756.
American Society for Biochemistry and Molecular