Almira Correia, PhD
Professor
Cellular Molecular Pharmacology
School of Medicine

Through extensive publications, we have investigated the structural determinants and regulatory pathways that govern the function and degradation of these enzymes. Our work on the other hemoproteins has also enabled us to shed light on the role of p62 in limiting NF-kB activation through stabilization of IkBa, the NF-kB-inhibitor, and to elucidate the underlying cause for inflammation in hepatic Mallory-Denk-Body induced conditions. Additionally, we have explored the therapeutic and pathophysiological aspects of impaired P450 degradation, and the consequent hepatic CYP2E1 elevation and its causal association with NAFLD/NASH. As the Principal Investigator on several NIH-sponsored projects, I have contributed significantly to advancing our understanding of hepatic cytochrome P450 enzymes and their regulation, opening up potential avenues for therapeutic interventions.

• Mitochondrial stress is relayed to the cytosol by an OMA1-DELE1-HRI pathway.
  Nature 2020 Guo X, Aviles G, Liu Y, Tian R, Unger BA, Lin YT, Wiita AP, Xu K, Correia MA, Kampmann M
• Cytochrome P450 endoplasmic reticulum-associated degradation (ERAD): therapeutic and pathophysiological implications.
  Acta pharmaceutica Sinica. B 2019 Kwon D, Kim SM, Correia MA
• Induction via Functional Protein Stabilization of Hepatic Cytochromes P450 upon gp78/Autocrine Motility Factor Receptor (AMFR) Ubiquitin E3-Ligase Genetic Ablation in Mice: Therapeutic and Toxicological Relevance.
  Molecular pharmacology 2019 Kwon D, Kim SM, Jacob P, Liu Y, Correia MA
• Molecular basis for catalysis and substrate-mediated cellular stabilization of human tryptophan 2,3-dioxygenase.
  Scientific reports 2016 Lewis-Ballester A, Forouhar F, Kim SM, Lew S, Wang Y, Karkashon S, Seetharaman J, Batabyal D, Chiang BY, Hussain M, Correia MA, Yeh SR, Tong L
• CHIP(-/-)-Mouse Liver: Adiponectin-AMPK-FOXO-Activation Overrides CYP2E1-Elicited JNK1-Activation, Delaying Onset of NASH: Therapeutic Implications.
  Scientific reports 2016 Kim SM, Grenert JP, Patterson C, Correia MA
• Hepatic cytochromes P450: structural degrons and barcodes, posttranslational modifications and cellular adapters in the ERAD-endgame.
  Drug metabolism reviews 2016 Kim SM, Wang Y, Nabavi N, Liu Y, Correia MA
• Human liver cytochrome P450 3A4 ubiquitination: molecular recognition by UBC7-gp78 autocrine motility factor receptor and UbcH5a-CHIP-Hsc70-Hsp40 E2-E3 ubiquitin ligase complexes.
  The Journal of biological chemistry 2014 Wang Y, Kim SM, Trnka MJ, Liu Y, Burlingame AL, Correia MA
• Hepatic cytochrome P450 ubiquitination: conformational phosphodegrons for E2/E3 recognition?
  IUBMB life 2014 Correia MA, Wang Y, Kim SM, Guan S
• Multisite phosphorylation of human liver cytochrome P450 3A4 enhances Its gp78- and CHIP-mediated ubiquitination: a pivotal role of its Ser-478 residue in the gp78-catalyzed reaction.
  Molecular & cellular proteomics : MCP 2011 Wang Y, Guan S, Acharya P, Liu Y, Thirumaran RK, Brandman R, Schuetz EG, Burlingame AL, Correia MA
• Ubiquitin-dependent proteasomal degradation of human liver cytochrome P450 2E1: identification of sites targeted for phosphorylation and ubiquitination.
  The Journal of biological chemistry 2011 Wang Y, Guan S, Acharya P, Koop DR, Liu Y, Liao M, Burlingame AL, Correia MA
• Liver cytochrome P450 3A endoplasmic reticulum-associated degradation: a major role for the p97 AAA ATPase in cytochrome P450 3A extraction into the cytosol.
  The Journal of biological chemistry 2010 Acharya P, Liao M, Engel JC, Correia MA
• Cytochrome P450 regulation: the interplay between its heme and apoprotein moieties in synthesis, assembly, repair, and disposal.
  Drug metabolism reviews 2010 Correia MA, Sinclair PR, De Matteis F
• Liver cytochrome P450 3A ubiquitination in vivo by gp78/autocrine motility factor receptor and C terminus of Hsp70-interacting protein (CHIP) E3 ubiquitin ligases: physiological and pharmacological relevance.
  The Journal of biological chemistry 2010 Kim SM, Acharya P, Engel JC, Correia MA
• Hepatic heme-regulated inhibitor (HRI) eukaryotic initiation factor 2alpha kinase: a protagonist of heme-mediated translational control of CYP2B enzymes and a modulator of basal endoplasmic reticulum stress tone.
  Molecular pharmacology 2010 Acharya P, Chen JJ, Correia MA
• Hepatic CYP3A suppression by high concentrations of proteasomal inhibitors: a consequence of endoplasmic reticulum (ER) stress induction, activation of RNA-dependent protein kinase-like ER-bound eukaryotic initiation factor 2alpha (eIF2alpha)-kinase (PERK) and general control nonderepressible-2 eIF2alpha kinase (GCN2), and global translational shutoff.
  Molecular pharmacology 2009 Acharya P, Engel JC, Correia MA
• A role for protein phosphorylation in cytochrome P450 3A4 ubiquitin-dependent proteasomal degradation.
  The Journal of biological chemistry 2008 Wang Y, Liao M, Hoe N, Acharya P, Deng C, Krutchinsky AN, Correia MA
• CYP3A4 ubiquitination by gp78 (the tumor autocrine motility factor receptor, AMFR) and CHIP E3 ligases.
  Archives of biochemistry and biophysics 2008 Pabarcus MK, Hoe N, Sadeghi S, Patterson C, Wiertz E, Correia MA
• Pathways of carbamazepine bioactivation in vitro. III. The role of human cytochrome P450 enzymes in the formation of 2,3-dihydroxycarbamazepine.
  Drug metabolism and disposition: the biological fate of chemicals 2008 Pearce RE, Lu W, Wang Y, Uetrecht JP, Correia MA, Leeder JS
• CYP3A4-Mediated carbamazepine (CBZ) metabolism: formation of a covalent CBZ-CYP3A4 adduct and alteration of the enzyme kinetic profile.
  Drug metabolism and disposition: the biological fate of chemicals 2007 Kang P, Liao M, Wester MR, Leeder JS, Pearce RE, Correia MA
• Impaired dexamethasone-mediated induction of tryptophan 2,3-dioxygenase in heme-deficient rat hepatocytes: translational control by a hepatic eIF2alpha kinase, the heme-regulated inhibitor.
  The Journal of pharmacology and experimental therapeutics 2007 Liao M, Pabarcus MK, Wang Y, Hefner C, Maltby DA, Medzihradszky KF, Salas-Castillo SP, Yan J, Maher JJ, Correia MA
• Characterization of the physiological turnover of native and inactivated cytochromes P450 3A in cultured rat hepatocytes: a role for the cytosolic AAA ATPase p97?
  Biochemistry 2007 Faouzi S, Medzihradszky KF, Hefner C, Maher JJ, Correia MA
• Cellular proteolytic systems in P450 degradation: evolutionary conservation from Saccharomyces cerevisiae to mammalian liver.
  Expert opinion on drug metabolism & toxicology 2007 Correia MA, Liao M
• Endoplasmic reticulum-associated degradation of cytochrome P450 CYP3A4 in Saccharomyces cerevisiae: further characterization of cellular participants and structural determinants.
  Molecular pharmacology 2006 Liao M, Faouzi S, Karyakin A, Correia MA
• Heme-reversible impairment of CYP2B1/2 induction in heme-depleted rat hepatocytes in primary culture: translational control by a hepatic alpha-subunit of the eukaryotic initiation factor kinase?
  The Journal of pharmacology and experimental therapeutics 2005 Han XM, Lee G, Hefner C, Maher JJ, Correia MA
• Vacuolar degradation of rat liver CYP2B1 in Saccharomyces cerevisiae: further validation of the yeast model and structural implications for the degradation of mammalian endoplasmic reticulum P450 proteins.
  Molecular pharmacology 2005 Liao M, Zgoda VG, Zgoda VA, Murray BP, Correia MA
• Cytochrome P450 ubiquitination: branding for the proteolytic slaughter?
  Annual review of pharmacology and toxicology 2005 Correia MA, Sadeghi S, Mundo-Paredes E
• Hepatic cytochrome P450 degradation: mechanistic diversity of the cellular sanitation brigade.
  Drug metabolism reviews 2003 Correia MA
• The changing environment of graduate and postdoctoral training in drug metabolism: viewpoints from academia, industry, and government.
  Drug metabolism and disposition: the biological fate of chemicals 2003 Stevens JC, Dean DC, Preusch PC, Correia MA
• Structure-function relationships of rat liver CYP3A9 to its human liver orthologs: site-directed active site mutagenesis to a progesterone dihydroxylase.
  Archives of biochemistry and biophysics 2003 Xue L, Zgoda VG, Arison B, Correia MA
• Hemin-mediated restoration of allylisopropylacetamide-inactivated CYP2B1: a role for glutathione and GRP94 in the heme-protein assembly.
  Archives of biochemistry and biophysics 2002 Gavrilovich Zgoda V, Arison B, Mkrtchian S, Ingelman-Sundberg M, Correia MA
• Differential oxidation of mifepristone by cytochromes P450 3A4 and 3A5: selective inactivation of P450 3A4.
  Drug metabolism and disposition: the biological fate of chemicals 2002 Khan KK, He YQ, Correia MA, Halpert JR
• Alcohol use and HIV pharmacotherapy.
  AIDS research and human retroviruses 2002 Kresina TF, Flexner CW, Sinclair J, Correia MA, Stapleton JT, Adeniyi-Jones S, Cargill V, Cheever LW
• Native CYP2C11: heterologous expression in Saccharomyces cerevisiae reveals a role for vacuolar proteases rather than the proteasome system in the degradation of this endoplasmic reticulum protein.
  Molecular pharmacology 2002 Murray BP, Zgoda VG, Correia MA
• Phosphorylation of native and heme-modified CYP3A4 by protein kinase C: a mass spectrometric characterization of the phosphorylated peptides.
  Biochemistry 2001 Wang X, Medzihradszky KF, Maltby D, Correia MA
• Ubiquitin-dependent 26S proteasomal pathway: a role in the degradation of native human liver CYP3A4 expressed in Saccharomyces cerevisiae?
  Archives of biochemistry and biophysics 2001 Murray BP, Correia MA
• Structure--function relationships of rat hepatic tryptophan 2,3-dioxygenase: identification of the putative heme-ligating histidine residues.
  Archives of biochemistry and biophysics 2001 Dick R, Murray BP, Reid MJ, Correia MA
• Influence of P450 3A4 SRS-2 residues on cooperativity and/or regioselectivity of aflatoxin B(1) oxidation.
  Chemical research in toxicology 2001 Xue L, Wang HF, Wang Q, Szklarz GD, Domanski TL, Halpert JR, Correia MA
• Heme: a regulator of rat hepatic tryptophan 2,3-dioxygenase?
  Archives of biochemistry and biophysics 2000 Ren S, Correia MA
• Ethynylestradiol-mediated induction of hepatic CYP3A9 in female rats: implication for cyclosporine metabolism.
  Drug metabolism and disposition: the biological fate of chemicals 1999 Jäger W, Correia MA, Bornheim LM, Mahnke A, Hanstein WG, Xue L, Benet LZ
• Cytochrome P450 3A degradation in isolated rat hepatocytes: 26S proteasome inhibitors as probes.
  Archives of biochemistry and biophysics 1999 Wang HF, Figueiredo Pereira ME, Correia MA
• Proteolytic degradation of heme-modified hepatic cytochromes P450: A role for phosphorylation, ubiquitination, and the 26S proteasome?
  Archives of biochemistry and biophysics 1999 Korsmeyer KK, Davoll S, Figueiredo-Pereira ME, Correia MA
• Identification of the heme-modified peptides from cumene hydroperoxide-inactivated cytochrome P450 3A4.
  Biochemistry 1998 He K, Bornheim LM, Falick AM, Maltby D, Yin H, Correia MA
• Structure-function relationships of human liver cytochromes P450 3A: aflatoxin B1 metabolism as a probe.
  Biochemistry 1998 Wang H, Dick R, Yin H, Licad-Coles E, Kroetz DL, Szklarz G, Harlow G, Halpert JR, Correia MA
• Cytochrome P450 2C11: Escherichia coli expression, purification, functional characterization, and mechanism-based inactivation of the enzyme.
  Archives of biochemistry and biophysics 1997 Licad-Coles E, He K, Yin H, Correia MA
• Secobarbital-mediated inactivation of cytochrome P450 2B1 and its active site mutants. Partitioning between heme and protein alkylation and epoxidation.
  The Journal of biological chemistry 1996 He K, He YA, Szklarz GD, Halpert JR, Correia MA
• Expression of rat liver tryptophan 2,3-dioxygenase in Escherichia coli: structural and functional characterization of the purified enzyme.
  Archives of biochemistry and biophysics 1996 Ren S, Liu H, Licad E, Correia MA
• Identification of the heme adduct and an active site peptide modified during mechanism-based inactivation of rat liver cytochrome P450 2B1 by secobarbital.
  Chemical research in toxicology 1996 He K, Falick AM, Chen B, Nilsson F, Correia MA
• Microsomal cytochrome P450-mediated liver and brain anandamide metabolism.
  Biochemical pharmacology 1995 Bornheim LM, Kim KY, Chen B, Correia MA
• Interactions of peroxyquinols with cytochromes P450 2B1, 3A1, and 3A5: influence of the apoprotein on heterolytic versus homolytic O-O bond cleavage.
  Archives of biochemistry and biophysics 1995 Correia MA, Yao K, Allentoff AJ, Wrighton SA, Thompson JA
• Cobaltous chloride-mediated induction of rat hepatic tryptophan 2,3-dioxygenase: implications for the use of the enzyme to probe the hepatic free heme pool.
  Cellular and molecular biology (Noisy-le-Grand, France) 1994 Liu H, Correia MA
• pH-dependent one- and two-electron oxidation of 3,5-dicarbethoxy-2,6-dimethyl-4-ethyl-1,4-dihydropyridine catalyzed by horseradish peroxidase.
  Chemical research in toxicology 1994 Sugiyama K, Correia MA, Thummel KE, Nagata K, Darbyshire JF, Osawa Y, Gillette JR
• Induction and genetic regulation of mouse hepatic cytochrome P450 by cannabidiol.
  Biochemical pharmacology 1994 Bornheim LM, Everhart ET, Li J, Correia MA
• Selective inhibitors of cytochromes P450.
  Toxicology and applied pharmacology 1994 Halpert JR, Guengerich FP, Bend JR, Correia MA
• The effect of cannabidiol on mouse hepatic microsomal cytochrome P450-dependent anandamide metabolism.
  Biochemical and biophysical research communications 1993 Bornheim LM, Kim KY, Chen B, Correia MA
• Cyclosporine metabolism by rat liver microsomes. Evidence for involvement of enzyme(s) other than cytochromes P-450 3A.
  Drug metabolism and disposition: the biological fate of chemicals 1993 Prueksaritanont T, Correia MA, Rettie AE, Swinney DC, Thomas PE, Benet LZ
• Characterization of cannabidiol-mediated cytochrome P450 inactivation.
  Biochemical pharmacology 1993 Bornheim LM, Everhart ET, Li J, Correia MA
• Cumene hydroperoxide-mediated inactivation of cytochrome P450 2B1. Identification of an active site heme-modified peptide.
  The Journal of biological chemistry 1993 Yao K, Falick AM, Patel N, Correia MA
• Matrix-assisted laser desorption mass spectrometry of cytochromes P450.
  Rapid communications in mass spectrometry : RCM 1993 Lewis S, Korsmeyer KK, Correia MA
• Degradation of rat liver cytochromes P450 3A after their inactivation by 3,5-dicarbethoxy-2,6-dimethyl-4-ethyl-1,4-dihydropyridine: characterization of the proteolytic system.
  Archives of biochemistry and biophysics 1992 Correia MA, Davoll SH, Wrighton SA, Thomas PE
• Differential apoprotein loss of rat liver cytochromes P450 after their inactivation by 3,5-dicarbethoxy-2,6-dimethyl-4-ethyl-1,4-dihydropyridine: a case for distinct proteolytic mechanisms?
  Archives of biochemistry and biophysics 1992 Correia MA, Yao K, Wrighton SA, Waxman DJ, Rettie AE
• Specifically designed thiosteroids as active-site-directed probes for functional dissection of rat liver cytochrome P450 3A isozymes.
  Chemical research in toxicology 1992 Underwood MC, Cashman JR, Correia MA
• Formation of glutathionyl-spironolactone disulfide by rat liver cytochromes P450 or hog liver flavin-containing monooxygenases: a functional probe of two-electron oxidations of the thiosteroid?
  Chemical research in toxicology 1991 Decker CJ, Cashman JR, Sugiyama K, Maltby D, Correia MA
• Purification and characterization of the major hepatic cannabinoid hydroxylase in the mouse: a possible member of the cytochrome P-450IIC subfamily.
  Molecular pharmacology 1991 Bornheim LM, Correia MA
• Cytochrome P450 turnover.
  Methods in enzymology 1991 Correia MA
• Selective inactivation of mouse liver cytochrome P-450IIIA by cannabidiol.
  Molecular pharmacology 1990 Bornheim LM, Correia MA
• Inactivation of rat hepatic cytochrome P-450 isozymes by 3,5-dicarbethoxy- 2,6-dimethyl-4-ethyl-1,4-dihydropyridine.
  Chemical research in toxicology 1989 Sugiyama K, Yao K, Rettie AE, Correia MA
• Effect of cannabidiol on cytochrome P-450 isozymes.
  Biochemical pharmacology 1989 Bornheim LM, Correia MA
• Purification and characterization of a mouse liver cytochrome P-450 induced by cannabidiol.
  Molecular pharmacology 1989 Bornheim LM, Correia MA
• Oxidative metabolism of spironolactone: evidence for the involvement of electrophilic thiosteroid species in drug-mediated destruction of rat hepatic cytochrome P450.
  Biochemistry 1989 Decker CJ, Rashed MS, Baillie TA, Maltby D, Correia MA
• Acute hepatic heme depletion: impaired gluconeogenesis in rats.
  Seminars in hematology 1989 Correia MA, Lunetta JM
• Degradation of rat hepatic cytochrome P-450p.
  Drug metabolism reviews 1989 Correia MA, Sugiyama K, Yao KQ
• Secobarbital-mediated inactivation of rat liver cytochrome P-450b: a mechanistic reappraisal.
  Molecular pharmacology 1989 Lunetta JM, Sugiyama K, Correia MA
• Role of gastrin/pentagastrin in regulation of intestinal cytochrome P-450.
  Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology 1988 Pascoe GA, Correia MA
• Degradation of rat hepatic cytochrome P-450 heme by 3,5-dicarbethoxy-2,6-dimethyl-4-ethyl-1,4-dihydropyridine to irreversibly bound protein adducts.
  Archives of biochemistry and biophysics 1987 Correia MA, Decker C, Sugiyama K, Caldera P, Bornheim L, Wrighton SA, Rettie AE, Trager WF
• Inactivation of multiple hepatic cytochrome P-450 isozymes in rats by allylisopropylacetamide: mechanistic implications.
  Molecular pharmacology 1987 Bornheim LM, Underwood MC, Caldera P, Rettie AE, Trager WF, Wrighton SA, Correia MA
• Drug-induced modulations of hepatic heme metabolism. Neurological consequences.
  Annals of the New York Academy of Sciences 1987 Correia MA, Litman DA, Lunetta JM
• Fractionation and purification of hepatic microsomal cytochrome P-450 isoenzymes from phenobarbital-pretreated rats by h.p.l.c. A convenient tool for screening of isoenzymes inactivated by allylisopropylacetamide.
  The Biochemical journal 1986 Bornheim LM, Correia MA