Almira Correia, PhD
Professor
As a Professor in the Cellular Molecular Pharmacology department at UCSF, my research has been centered on the elucidation of key molecular mechanisms involved in the function and regulation of hepatic cytochrome P450 enzymes (P450s) and other physiologically important hemoproteins. 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.
Publications
Liu Y, Trnka MJ, He L, Burlingame AL, Correia MA. In-cell chemical crosslinking identifies hotspots for SQSTM-1/p62-I?Ba interaction that underscore a critical role of p62 in limiting NF-?B activation through I?Ba-stabilization. Molecular & cellular proteomics : MCP 2023. PMID: 36634736
Liu Y, Kim SM, Wang Y, Karkashon S, Lewis-Ballester A, Yeh SR, Correia MA. Characterization of the structural determinants of the ubiquitin-dependent proteasomal degradation of human hepatic tryptophan 2,3-dioxygenase. 2021. PMID: 33960368
Correia MA, Kwon D. Why Hepatic CYP2E1-Elevation by Itself Is Insufficient for Inciting NAFLD/NASH: Inferences from Two Genetic Knockout Mouse Models. 2020. PMID: 33255949
Liu Y, Trnka MJ, Guan S, Kwon D, Kim DH, Chen JJ, Greer PA, Burlingame AL, Correia MA. A Novel Mechanism For NF-?B Activation Via I?B Aggregation: Implications For Hepatic Mallory-Denk-Body Induced Inflammation. Molecular & cellular proteomics : MCP 2020. PMID: 32912968
Guo X, Aviles G, Liu Y, Tian R, Unger BA, Lin YT, Wiita AP, Xu K, Correia MA, Kampmann M. Mitochondrial stress is relayed to the cytosol by an OMA1-DELE1-HRI pathway. Nature 2020. PMID: 32132707
Kwon D, Kim SM, Correia MA. Cytochrome P450 endoplasmic reticulum-associated degradation (ERAD): therapeutic and pathophysiological implications. Acta pharmaceutica Sinica. B 2019. PMID: 31993306
Kwon D, Kim S, Jacob P, Liu Y, 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. PMID: 31492698
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. Molecular basis for catalysis and substrate-mediated cellular stabilization of human tryptophan 2,3-dioxygenase. Volume 6. Scientific Reports 2016. PMID: 27762317
Kim SM, Grenert JP, Patterson C, Correia MA. CHIP(-/-)-Mouse Liver: Adiponectin-AMPK-FOXO-Activation Overrides CYP2E1-Elicited JNK1-Activation, Delaying Onset of NASH: Therapeutic Implications. Volume 6. Scientific Reports 2016. PMID: 27406999
Kim SM, Wang Y, Nabavi N, Liu Y, Correia MA. Hepatic cytochromes P450: structural degrons and barcodes, posttranslational modifications and cellular adapters in the ERAD-endgame. Volume 48 of Issue 3. Drug metabolism reviews 2016. PMID: 27320797
Wang Y, Kim SM, Trnka MJ, Liu Y, Burlingame AL, 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. Volume 290 of Issue 6. The Journal of biological chemistry 2014. PMID: 25451919
Correia MA, Wang Y, Kim SM, Guan S. Hepatic cytochrome P450 ubiquitination: conformational phosphodegrons for E2/E3 recognition? Volume 66 of Issue 2. IUBMB life 2014. PMID: 24488826
Wang Y, Guan S, Acharya P, Liu Y, Thirumaran RK, Brandman R, Schuetz EG, Burlingame AL, Correia MA. 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. Volume 11 of Issue 2. Molecular & cellular proteomics : MCP 2011. PMID: 22101235
Wang Y, Guan S, Acharya P, Koop DR, Liu Y, Liao M, Burlingame AL, Correia MA. Ubiquitin-dependent proteasomal degradation of human liver cytochrome P450 2E1: identification of sites targeted for phosphorylation and ubiquitination. Volume 286 of Issue 11. The Journal of biological chemistry 2011. PMID: 21209460
Acharya P, Liao M, Engel JC, 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. PMID: 21107009
Correia MA, Sinclair PR, De Matteis F. Cytochrome P450 regulation: the interplay between its heme and apoprotein moieties in synthesis, assembly, repair, and disposal. Volume 43 of Issue 1. Drug metabolism reviews 2010. PMID: 20860521
Kim SM, Acharya P, Engel JC, Correia MA. 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. Volume 285 of Issue 46. The Journal of biological chemistry 2010. PMID: 20819951
Acharya P, Chen JJ, 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. PMID: 20071449
Acharya P, Engel JC, 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 Molecular pharmacology 2009. PMID: 19520899
Wang Y, Liao M, Hoe N, Acharya P, Deng C, Krutchinsky AN, Correia MA. A role for protein phosphorylation in cytochrome P450 3A4 ubiquitin-dependent proteasomal degradation. Volume 284 of Issue 9. The Journal of biological chemistry 2008. PMID: 19095658
Pabarcus MK, Hoe N, Sadeghi S, Patterson C, Wiertz E, Correia MA. CYP3A4 ubiquitination by gp78 (the tumor autocrine motility factor receptor, AMFR) and CHIP E3 ligases. Volume 483 of Issue 1. Archives of biochemistry and biophysics 2008. PMID: 19103148
Pearce RE, Lu W, Wang Y, Uetrecht JP, Correia MA, Leeder JS. Pathways of carbamazepine bioactivation in vitro. III. The role of human cytochrome P450 enzymes in the formation of 2,3-dihydroxycarbamazepine. Volume 36 of Issue 8. Drug metabolism and disposition: the biological fate of chemicals 2008. PMID: 18463198
Kang P, Liao M, Wester MR, Leeder JS, Pearce RE, Correia MA. CYP3A4-Mediated carbamazepine (CBZ) metabolism: formation of a covalent CBZ-CYP3A4 adduct and alteration of the enzyme kinetic profile. Volume 36 of Issue 3. Drug metabolism and disposition: the biological fate of chemicals 2007. PMID: 18096676
Liao M, Pabarcus MK, Wang Y, Hefner C, Maltby DA, Medzihradszky KF, Salas-Castillo SP, Yan J, Maher JJ, 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. Volume 323 of Issue 3. The Journal of pharmacology and experimental therapeutics 2007. PMID: 17761498
Faouzi S, Medzihradszky KF, Hefner C, 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? Volume 46 of Issue 26. Biochemistry 2007. PMID: 17550236
Correia MA, Liao M. Cellular proteolytic systems in P450 degradation: evolutionary conservation from Saccharomyces cerevisiae to mammalian liver. Volume 3 of Issue 1. Expert opinion on drug metabolism & toxicology 2007. PMID: 17269893
Liao M, Faouzi S, Karyakin A, Correia MA. Endoplasmic reticulum-associated degradation of cytochrome P450 CYP3A4 in Saccharomyces cerevisiae: further characterization of cellular participants and structural determinants. Volume 69 of Issue 6. Molecular pharmacology 2006. PMID: 16556771
Han XM, Lee G, Hefner C, Maher JJ, 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? Volume 314 of Issue 1. The Journal of pharmacology and experimental therapeutics 2005. PMID: 15769864
Liao M, Zgoda VG, Zgoda VA, Murray BP, 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. Volume 67 of Issue 5. Molecular pharmacology 2005. PMID: 15703377
Correia MA, Sadeghi S, Mundo-Paredes E. Cytochrome P450 ubiquitination: branding for the proteolytic slaughter? Volume 45. Annual review of pharmacology and toxicology 2005. PMID: 15822184
Correia MA. Hepatic cytochrome P450 degradation: mechanistic diversity of the cellular sanitation brigade. Volume 35 of Issue 2-3. Drug metabolism reviews 2003. PMID: 12959413
Stevens JC, Dean DC, Preusch PC, 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. PMID: 12642460
Xue L, Zgoda VG, Arison B, Correia MA. Structure-function relationships of rat liver CYP3A9 to its human liver orthologs: site-directed active site mutagenesis to a progesterone dihydroxylase. Volume 409 of Issue 1. Archives of biochemistry and biophysics 2003. PMID: 12464250
Gavrilovich Zgoda V, Arison B, Mkrtchian S, Ingelman-Sundberg M, Correia MA. Hemin-mediated restoration of allylisopropylacetamide-inactivated CYP2B1: a role for glutathione and GRP94 in the heme-protein assembly. Volume 408 of Issue 1. Archives of biochemistry and biophysics 2002. PMID: 12485603
Khan KK, He YQ, Correia MA, Halpert JR. Differential oxidation of mifepristone by cytochromes P450 3A4 and 3A5: selective inactivation of P450 3A4. Volume 30 of Issue 9. Drug metabolism and disposition: the biological fate of chemicals 2002. PMID: 12167563
Kresina TF, Flexner CW, Sinclair J, Correia MA, Stapleton JT, Adeniyi-Jones S, Cargill V, Cheever LW. Alcohol use and HIV pharmacotherapy. AIDS research and human retroviruses 2002. PMID: 12167267
Murray BP, Zgoda VG, Correia MA. 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. Volume 61 of Issue 5. Molecular pharmacology 2002. PMID: 11961133
Wang X, Medzihradszky KF, Maltby D, Correia MA. Phosphorylation of native and heme-modified CYP3A4 by protein kinase C: a mass spectrometric characterization of the phosphorylated peptides. Volume 40 of Issue 38. Biochemistry 2001. PMID: 11560479
Murray BP, Correia MA. Ubiquitin-dependent 26S proteasomal pathway: a role in the degradation of native human liver CYP3A4 expressed in Saccharomyces cerevisiae? Volume 393 of Issue 1. Archives of biochemistry and biophysics 2001. PMID: 11516167
Dick R, Murray BP, Reid MJ, Correia MA. Structure--function relationships of rat hepatic tryptophan 2,3-dioxygenase: identification of the putative heme-ligating histidine residues. Volume 392 of Issue 1. Archives of biochemistry and biophysics 2001. PMID: 11469796
Xue L, Wang HF, Wang Q, Szklarz GD, Domanski TL, Halpert JR, Correia MA. Influence of P450 3A4 SRS-2 residues on cooperativity and/or regioselectivity of aflatoxin B(1) oxidation. Volume 14 of Issue 5. Chemical research in toxicology 2001. PMID: 11368545
Ren S, Correia MA. Heme: a regulator of rat hepatic tryptophan 2,3-dioxygenase? Volume 377 of Issue 1. Archives of biochemistry and biophysics 2000. PMID: 10775460
Jäger W, Correia MA, Bornheim LM, Mahnke A, Hanstein WG, Xue L, Benet LZ. Ethynylestradiol-mediated induction of hepatic CYP3A9 in female rats: implication for cyclosporine metabolism. Volume 27 of Issue 12. Drug metabolism and disposition: the biological fate of chemicals 1999. PMID: 10570034
Wang HF, Figueiredo Pereira ME, Correia MA. Cytochrome P450 3A degradation in isolated rat hepatocytes: 26S proteasome inhibitors as probes. Volume 365 of Issue 1. Archives of biochemistry and biophysics 1999. PMID: 10222037
Korsmeyer KK, Davoll S, Figueiredo-Pereira ME, Correia MA. Proteolytic degradation of heme-modified hepatic cytochromes P450: A role for phosphorylation, ubiquitination, and the 26S proteasome? Volume 365 of Issue 1. Archives of biochemistry and biophysics 1999. PMID: 10222036
He K, Bornheim LM, Falick AM, Maltby D, Yin H, Correia MA. Identification of the heme-modified peptides from cumene hydroperoxide-inactivated cytochrome P450 3A4. Volume 37 of Issue 50. Biochemistry 1998. PMID: 9860860
Wang H, Dick R, Yin H, Licad-Coles E, Kroetz DL, Szklarz G, Harlow G, Halpert JR, Correia MA. Structure-function relationships of human liver cytochromes P450 3A: aflatoxin B1 metabolism as a probe. Volume 37 of Issue 36. Biochemistry 1998. PMID: 9730826
Licad-Coles E, He K, Yin H, Correia MA. Cytochrome P450 2C11: Escherichia coli expression, purification, functional characterization, and mechanism-based inactivation of the enzyme. Volume 338 of Issue 1. Archives of biochemistry and biophysics 1997. PMID: 9015385
He K, He YA, Szklarz GD, Halpert JR, Correia MA. Secobarbital-mediated inactivation of cytochrome P450 2B1 and its active site mutants. Partitioning between heme and protein alkylation and epoxidation. Volume 271 of Issue 42. The Journal of biological chemistry 1996. PMID: 8824218
Ren S, Liu H, Licad E, Correia MA. Expression of rat liver tryptophan 2,3-dioxygenase in Escherichia coli: structural and functional characterization of the purified enzyme. Volume 333 of Issue 1. Archives of biochemistry and biophysics 1996. PMID: 8806758
He K, Falick AM, Chen B, Nilsson F, 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. Volume 9 of Issue 3. Chemical research in toxicology 1996. PMID: 8728507
Bornheim LM, Kim KY, Chen B, Correia MA. Microsomal cytochrome P450-mediated liver and brain anandamide metabolism. Volume 50 of Issue 5. Biochemical pharmacology 1995. PMID: 7669071
Correia MA, Yao K, Allentoff AJ, Wrighton SA, Thompson JA. Interactions of peroxyquinols with cytochromes P450 2B1, 3A1, and 3A5: influence of the apoprotein on heterolytic versus homolytic O-O bond cleavage. Volume 317 of Issue 2. Archives of biochemistry and biophysics 1995. PMID: 7893165
Liu H, Correia MA. 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. Volume 40 of Issue 7. Cellular and molecular biology (Noisy-le-Grand, France) 1994. PMID: 7849555
Sugiyama K, Correia MA, Thummel KE, Nagata K, Darbyshire JF, Osawa Y, Gillette JR. pH-dependent one- and two-electron oxidation of 3,5-dicarbethoxy-2,6-dimethyl-4-ethyl-1,4-dihydropyridine catalyzed by horseradish peroxidase. Volume 7 of Issue 5. Chemical research in toxicology 1994. PMID: 7841342
Bornheim LM, Everhart ET, Li J, Correia MA. Induction and genetic regulation of mouse hepatic cytochrome P450 by cannabidiol. Volume 48 of Issue 1. Biochemical pharmacology 1994. PMID: 8043019
Halpert JR, Guengerich FP, Bend JR, Correia MA. Selective inhibitors of cytochromes P450. Volume 125 of Issue 2. Toxicology and applied pharmacology 1994. PMID: 8171425
Bornheim LM, Kim KY, Chen B, Correia MA. The effect of cannabidiol on mouse hepatic microsomal cytochrome P450-dependent anandamide metabolism. Volume 197 of Issue 2. Biochemical and biophysical research communications 1993. PMID: 8267610
Prueksaritanont T, Correia MA, Rettie AE, Swinney DC, Thomas PE, Benet LZ. Cyclosporine metabolism by rat liver microsomes. Evidence for involvement of enzyme(s) other than cytochromes P-450 3A. Volume 21 of Issue 4. Drug metabolism and disposition: the biological fate of chemicals 1993. PMID: 8104135
Bornheim LM, Everhart ET, Li J, Correia MA. Characterization of cannabidiol-mediated cytochrome P450 inactivation. Volume 45 of Issue 6. Biochemical pharmacology 1993. PMID: 8466552
Yao K, Falick AM, Patel N, Correia MA. Cumene hydroperoxide-mediated inactivation of cytochrome P450 2B1. Identification of an active site heme-modified peptide. Volume 268 of Issue 1. The Journal of biological chemistry 1993. PMID: 8416964
Lewis S, Korsmeyer KK, Correia MA. Matrix-assisted laser desorption mass spectrometry of cytochromes P450. Volume 7 of Issue 1. Rapid communications in mass spectrometry : RCM 1993. PMID: 8428024
Correia MA, Davoll SH, Wrighton SA, Thomas PE. 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. Volume 297 of Issue 2. Archives of biochemistry and biophysics 1992. PMID: 1497342
Correia MA, Yao K, Wrighton SA, Waxman DJ, Rettie AE. 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? Volume 294 of Issue 2. Archives of biochemistry and biophysics 1992. PMID: 1567205
Underwood MC, Cashman JR, Correia MA. Specifically designed thiosteroids as active-site-directed probes for functional dissection of rat liver cytochrome P450 3A isozymes. Volume 5 of Issue 1. Chemical research in toxicology 1992. PMID: 1581535
Decker CJ, Cashman JR, Sugiyama K, Maltby D, 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? Volume 4 of Issue 6. Chemical research in toxicology 1991. PMID: 1807450
Bornheim LM, Correia MA. Purification and characterization of the major hepatic cannabinoid hydroxylase in the mouse: a possible member of the cytochrome P-450IIC subfamily. Volume 40 of Issue 2. Molecular pharmacology 1991. PMID: 1875910
Correia MA. Cytochrome P450 turnover. Volume 206. Methods in enzymology 1991. PMID: 1784218
Bornheim LM, Correia MA. Selective inactivation of mouse liver cytochrome P-450IIIA by cannabidiol. Volume 38 of Issue 3. Molecular pharmacology 1990. PMID: 2402224
Sugiyama K, Yao K, Rettie AE, Correia MA. Inactivation of rat hepatic cytochrome P-450 isozymes by 3,5-dicarbethoxy- 2,6-dimethyl-4-ethyl-1,4-dihydropyridine. Volume 2 of Issue 6. Chemical research in toxicology 1989. PMID: 2519730
Bornheim LM, Correia MA. Effect of cannabidiol on cytochrome P-450 isozymes. Volume 38 of Issue 17. Biochemical pharmacology 1989. PMID: 2550010
Bornheim LM, Correia MA. Purification and characterization of a mouse liver cytochrome P-450 induced by cannabidiol. Volume 36 of Issue 3. Molecular pharmacology 1989. PMID: 2779523
Decker CJ, Rashed MS, Baillie TA, Maltby D, Correia MA. Oxidative metabolism of spironolactone: evidence for the involvement of electrophilic thiosteroid species in drug-mediated destruction of rat hepatic cytochrome P450. Volume 28 of Issue 12. Biochemistry 1989. PMID: 2765527
Correia MA, Lunetta JM. Acute hepatic heme depletion: impaired gluconeogenesis in rats. Volume 26 of Issue 2. Seminars in hematology 1989. PMID: 2471273
Correia MA, Sugiyama K, Yao KQ. Degradation of rat hepatic cytochrome P-450p. Volume 20 of Issue 2-4. Drug metabolism reviews 1989. PMID: 2680399
Lunetta JM, Sugiyama K, Correia MA. Secobarbital-mediated inactivation of rat liver cytochrome P-450b: a mechanistic reappraisal. Volume 35 of Issue 1. Molecular pharmacology 1989. PMID: 2913483
Pascoe GA, Correia MA. Role of gastrin/pentagastrin in regulation of intestinal cytochrome P-450. Volume 90 of Issue 1. Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology 1988. PMID: 2904872
Correia MA, Decker C, Sugiyama K, Caldera P, Bornheim L, Wrighton SA, Rettie AE, Trager WF. 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. Volume 258 of Issue 2. Archives of biochemistry and biophysics 1987. PMID: 3674884
Bornheim LM, Underwood MC, Caldera P, Rettie AE, Trager WF, Wrighton SA, Correia MA. Inactivation of multiple hepatic cytochrome P-450 isozymes in rats by allylisopropylacetamide: mechanistic implications. Volume 32 of Issue 1. Molecular pharmacology 1987. PMID: 3302670
Correia MA, Litman DA, Lunetta JM. Drug-induced modulations of hepatic heme metabolism. Neurological consequences. Volume 514. Annals of the New York Academy of Sciences 1987. PMID: 3442388
Bornheim LM, Correia MA. 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. Volume 239 of Issue 3. The Biochemical journal 1986. PMID: 3827818