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Faculty Detail    
Name ALEXANDER J SZALAI
 
Campus Address SHEL 214 Zip 2182
Phone  (20-5) -241
E-mail  AlexSzalai@uab.edu
Other websites
     

Education
Graduate  The University of Manitoba    1990  PhD 


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Medicine  Med - Immunology/Rheumatology Professor
Center  Comp Arthritis, MSK, Bone & Autoimmunity Ctr  Comp Arthritis, MSK, Bone & Autoimmunity Ctr Professor
Center  Comprehensive Diabetes Center  Comprehensive Diabetes Center Professor
Center  General Clinical Research Center  Ctr for Clinical & Translational Sci Professor
Center  Medicine  Ctr Cardiovasc Bio (Org Ret) Professor
Center  Neurology   Multiple Sclerosis Center Professor
Center  General Clinical Research Center  Nephrology Research & Training Center Professor
Center  Nutrition Sciences   Nutrition Obesity Res Ctr (NORC) Professor

Graduate Biomedical Sciences Affiliations
Cell, Molecular, & Developmental Biology 
Cellular and Molecular Biology Program 
Genetics, Genomics and Bioinformatics 
Immunology 

Biographical Sketch 
Foreign Languages Francois (Read - Functional, Write - Basic, Speak - Basic, Understand - Functional) Magyar (Read - Functional, Write - Basic, Speak - Fluent, Understand - Fluent) Professional Consulting 1996 - present: Biocryst Pharmaceuticals Inc., Birmingham, AL. 2001: Aventis Pasteur Limited, Toronto, Canada 2002: Merck Research Laboratories, Rahway, NJ 2002 present: Pfizer, Ann Arbor Research Laboratories, Ann Arbor, MI 2003: Lilly Research Laboratories, Indianapolis, IN 2003 present: Gerson Lehrman Group Council of Healthcare Advisors 2004 Inflabloc Pharmaceuticals, Inc. 2003 - 2004 Rejuvenon Corp. 2004 Boehringer-Ingelheim Pharmaceuticals, Inc. Education The University of Manitoba, Winnipeg, MB, Canada, B.S., Dean's Honor list, 1984 The University of Manitoba, Winnipeg, MB, Canada, Master Of Science, Zoology, 1986 The University of Manitoba, Winnipeg, MB, Canada, Ph.D., Parasitology, 1990 Postdoctoral Training 1990 - 1992: Dept. Microbiology, The University of Mississippi Medical Center, Jackson, MS 1992 - 1993: Dept. Biochemistry, Memorial University of Newfoundland, St. John's, NF, Canada Academic Appointments 2004-Present: Associate Professor, Dept. Medicine, Div. Clinical Immunology and Rheumatology, UAB 2001-2004: Research Associate Professor, Div. Clinical Immunology and Rheumatology, UAB 1998-Present: Associate Scientist, Arthritis and Musculoskeletal Center, UAB 1996-2001: Research Assistant Professor, Div. Clinical Immunology and Rheumatology, UAB 1993-1996: Research Instructor, Div. Clinical Immunology and Rheumatology, UAB Awards and Honors 1986-1987: Graduate Student Fellowship 1986-1988: Postgraduate Scholarship 1988: George A. Lubinsky memorial scholarship 1989-1991: Postdoctoral Fellowship 1991: Travel Scholarship 1999: USA Permanent Residency (Outstanding Professor or Scientist) 2000: MARQUIS Who's Who in Science and Engineering (5th Ed) 2003: cover article highlighted by Arthritis & Rheumatism (Vol. 48 no. 6) 2003: cover article highlighted by Circulation (Vol. 108 no. 5) 2004: Concurrent Session Chairperson: 4th International Congress on Autoimmunity. Budapest, Hungary Scientific and Professional Societies American Association for the Advancement of Science American Association of Immunologists Federation of American Societies for Experimental Biology American Society For Microbiology National Multiple Sclerosis Society

Society Memberships
Organization Name Position Held Org Link
American Heart Association  Study Section Member   



Research/Clinical Interest
Title
Inflammation, innate immunity, and the acute phase proteins in health and disease
Description
Dr. Szalai is collaborating extensively with several members of the faculty in a series of integrated studies of C-reactive protein (CRP), complement, and Fc receptors; different components of the innate immune system. These studies currently include analysis of the mechanisms that operate to affect the host defense function of CRP and complement against pathogens (Streptococcus pneumoniae), the role of CRP and complement in autoimmune diseases (SLE, MS), and the role of CRP in cardiovascular diseases (atherosclerosis, restenosis, heart transplant rejection). CRP is a 110-kDa protein made up of five identical subunits. It binds phosphocholine, activates the classical pathway of complement, and is recognized by FcgRI and FcgRII. CRP specifically recognizes pathogenic microorganisms and damaged cells of the host and initiates their elimination. Dr. Szalai has used CRP-transgenic mice (CRPtg) to dissect the mechanisms operating to affect the innate host defense function of CRP. His investigations established that CRP-dependent protection against pathogens, such as Streptococcus pneumoniae and Salmonella typhimurium, is effected mainly by clearance of pathogens during the early post-infection period. Complement is not required for this function. In parallel studies of the mode of induction of the CRP gene in vivo, testosterone was found to control basal expression; whereas complement protein 5a, acting together with pro-inflammatory cytokines, is critical for acute-phase induction of CRP. Current studies include determination of the contribution of Fc receptors to CRP-mediated protection using CRPtg/FcgR-deficient mice, and analysis of the effects of CRP expression on serum antibody responses. In addition, Dr. Szalai actively participates in several clinical studies, and is now investigating allelic differences in the expression of CRP in healthy versus diseased individuals. CRP is routinely used as a plasma marker of inflammation in inflammatory diseases. As family studies have demonstrated genetic influences in SLE, with linkage to several regions on human chromosome 1 and the CRP gene is located within one candidate linkage region, genetic differences in this gene could be related to the lupus diathesis. Dr. Szalai has evaluatied the association of a (GT) repeat polymorphism in the intron of the CRP gene with plasma levels of CRP and the clinical phenotype of SLE in collaboration with Dr. Robert P. Kimberly. Finally, Dr. Szalai is using two different mouse models to determine the role of CRP in the development of autoimmune disease. CRP-transgenic (NZB X NZW)F1 mice (BW) exhibited delayed onset of SLE and their lifespan was extended significantly compared to that of non-transgenic BW mice. However, the anti-double stranded DNA autoimmune response occurred earlier and was enhanced in the CRP-transgenic mice, and there was deposition of CRP in nephritic kidneys. Current studies seek to determine the mechanism for the CRP-protective effect. The onset of experimental allergic encephalomyelitis (EAE, a model for MS) is delayed in female CRP-transgenic mice compared to wild-type mice. This protective effect is causally related to the transient upregulation of the CRP transgene observed during the early stages of disease development. In collaboration with Dr. Scott Barnum, Dr. Szalai is now testing the hypothesis that the duration of CRP-mediated protection against EAE will be extended in CRP-transgenic mice by prolonging and/or increasing expression of CRP, which may be achieved through the influence of sex hormones that regulate CRP expression. Mutant mice that are not able to fully activate the complement system due to engineered deficiency in C3 or factor B, exhibit reduced clinical symptoms of EAE, cellular infiltration, and demyelination. When complement-deficient mice hybridized with CRP-transgenic mice were tested, a delay in both the CRP-mediated delay in onset of EAE and the complement deficiency-mediated reduction of disease were observed. These data show that the CRP-protective effect in EAE is realized whether or not a fully functional complement system is present, suggesting that CRP is mediating its protection through other mechanisms. Dr. Szalai's most recent work, performed in collaboration with groups at Harvard, UCSD, Baylor, and UAB, showed that CRPtg mice exhibit ia pro-thrombotic/pro-atherosclerotic phenotype, but experience reduced neointimal growth following vascular injury.

Selected Publications 
Publication PUBMEDID
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PUBLICATIONS SINCE 2012

Zhou J, Ouyang X, Schoeb TR, Bolisetty S, Cui X, Mrug S, Yoeder BK, Johnson MR, Szalai AJ, and M Mrug. Kidney injury accelerates cystogenesis via pathways modulated by heme oxygenase and complement. Journal of the American Society of Nephrology. 2012. 23:1161-1171.

Ashraf A, Fisher G, Alvarez J, Dudenbostel T, Calhoun D, Szalai AJ, and Gower BA. Associations of C-reactive protein to indices of vascular health and the influence of serum 25(OH)D status in healthy adults. The Journal of Nutrition & Metabolism. 2012. vol. 2012, Article ID 475975, 6 pages, doi:10.1155/2012/475975

Jones NR , Pegues MA, McCrory MA, Singleton W, Bethune C, Baker BF, Norris DA, Crooke RM, Graham MJ, and Szalai AJ. A selective inhibitor of human C-reactive protein translation is efficacious in vitro and in C-reactive protein transgenic mice and humans. Molecular Therapy- Nucleic Acids 2012. 1: e52; doi:10.1038/mtna.2012.44

Mukerji R, Mirza S, Roche AF, Widener R, Rhee DK, Weiser JN, Szalai AJ and DE Briles. Pneumococcal surface protein A (PspA) inhibits complement deposition on the pneumococcal surface by competing with the binding of C-reactive protein (CRP) to cell-surface phosphorylcholine. The Journal of Immunology 2012. 189:5327-5335

Pegues MA, McCrory MA, Zarjou A, and AJ Szalai. C-reactive protein exacerbates renal ischemia reperfusion injury. American Journal of Physiology – Renal Physiology 2013. 304:F1358-65

Zhou Y, Wu J, Kucik DF, White NB, Redden DT, Szalai AJ, Bullard DC, and Edberg JC. Multiple lupus associated ITGAM variants alter Mac-1 function on neutrophils. Arthritis & Rheumatism. 2013. 65:2907-2916

Tang Y, X-R Huang, J Lu, ACK Chung, Y Zhang, JZ Chen, AJ Szalai, A Xu, and HY Lan. C-reactive protein promotes acute kidney injury by impairing the G1/S-dependent tubular epithelial cell regeneration. Clinical Science. 2014. 126:645-659

Szalai AJ, McCrory M, Xing D, Hage FG, Miller A, Oparil S, Chen YF, Mazzone M, Early R, Henry SP, Zanardi TA, Graham MA, and Crooke RM. Inhibiting C-reactive protein for the treatment of cardiovascular disease: Promising evidence from rodent models. Mediators of Inflammation. 2014. Volume 2014, Article ID 353614

Zhou Y, Kucik DF, Szalai AJ, Bullard DC, and Edberg JC. Human Neutrophil Flow Chamber Adhesion Assay. Journal of Visualized Experiments. 2014. In press

Bowling MR, D Xing, A Kapadia, Y-F Chen, AJ Szalai, S Oparil, and FG Hage. Estrogen effects on vascular inflammation are age-dependent. Arteriosclerosis Thrombosis and Vascular Biology. 2014. In press

Owsley C, C Huisingh, GR Jackson, CA Curcio, AJ Szalai, N Dashti, M Clark, K Rookard, MA McCrory, TT Wright, MA Callahan, L Kline, CD Witherspoon and G McGwin Jr. Associations between Abnormal Rod-Mediated Dark Adaptation and Health and Functioning in Older Adults with Normal Macular Health. Investigative Ophthalmology and Visual Science. 2014. In press

AJ Szalai, SR Barnum, and TN Ramos. Deletion of C-reactive protein ameliorates experimental cerebral malaria? Transactions of the Royal Society of Tropical Medicine and Hygiene. 2014. In press
 
 
Jones SA, D Novick, S Horiuchi, N Yamamoto, AJ Szalai, and GM Fuller: C-reactive protein: A physiological activator of interleukin 6 receptor shedding. Journal of Experimental Medicine 189:599-604, 1999.   9927522 
Szalai AJ, FW van Ginkel, SA Dalrymple, R Murray, JR McGhee, and JE Volanakis: Testosterone and IL-6 requirements for human C-reactive protein gene expression in transgenic mice. Journal of Immunology 160:5294-5299, 1998.   9605127 
Szalai AJ. C-reactive protein and autoimmune disease: Facts and Conjectures. Clinical and Developmental Immunology. 11:221-226, 2004  15559367 
Verschuren L, R Kleeman, EH Offerman, AJ Szalai, SJ Emeis, HMG Princen, and T Kooistra. Effect of low dose atorvastatin versus diet-induced cholesterol-lowering on atherosclerotic lesion progression and inflammation in ApoE*3-Leiden transgenic mice. Arteriosclerosis, Thrombosis, and Vascular Biology, In press, 2004   15514207 
Szalai AJ and SR Barnum. Fc receptors and the common ƒ×-chain in experimental autoimmune encephalitis. Journal of Neuroscience Research. 75:597-602, 2004.  14991835 
Paul A, KWS Ko, L Li, V Yechoor, MA McCrory, AJ Szalai, and L Chan. C-reactive protein accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice. Circulation. 109: 647 – 655, 2004   14744975 
Danenberg HD, AJ Szalai, RV Swaminathan, L Peng, Z Chen, P Seifert, WP Fay, DI Simon, and ER Edelman. Increased arterial thrombosis following arterial injury in human C-reactive protein transgenic mice. Circulation. 108:512-515, 2003 (issue highlight)   12874178 
Xu Y, AJ Szalai, T Zhou, KR Zinn, TR Chaudhuri, X Li, WJ Koopman, and RP Kimberly. FcgRs modulate cytotoxicity of anti-Fas antibodies: implications for agonistic antibody-based therapeutics. The Journal of Immunology. 171:562-568, 2003   12847219 
Szalai AJ, CT Weaver, MA McCrory, FW van Ginkel, RM Reiman, TN Marion, and JE Volanakis. Delayed lupus onset in (NZBxNZW)F1 mice expressing a human C-reactive protein transgene. Arthritis & Rheumatism. 48:1602-1611, 2003 (issue highlight)   12794828 
Szalai AJ, Nataf S, Xian-Zhen Hu, and SR Barnum: Experimental allergic encephalomyelitis is inhibited in trangenic mice expressing C-reactive protein. Journal of Immunology. 168: 5792-5797, 2002.   12023381 
Szalai AJ, McCrory M, Cooper GS, Wu J, and RP Kimberly: Association between baseline levels of C-reactive protein (CRP) and a dinucleotide repeat polymorphism in the intron of the CRP gene. Genes and Immunity, 3:14-19, 2002.   11857055 
Szalai AJ, JL VanCott, JR McGhee, JE Volanakis, and WH Benjamin, Jr.: Human C-reactive protein is protective against fatal Salmonella enterica serovar typhimurium infection in transgenic mice. Infect. & Immunity 68(10): 5652-5656, 2000.   10992466 
Szalai AJ, FW van Ginkel, Y Wang, JR McGhee, and JE Volanakis: Complement-dependent acute-phase expression of C-reactive protein and serum amyloid P-component. Journal of Immunology 165:1030-1035, 2000.   10878380 
Chen K, Li F, Li J, Cai H, Strom S, Bisello A, Kelley DE, Friedman-Einat M, Skibinski GA, McCrory MA, Szalai AJ, Zhao AZ. Induction of leptin resistance through direct interaction of C-reactive protein with leptin. Nature Medicine, 2006, 12:425-432.   
Wang D, Oparil S, Chen Y-F, McCrory MA, Feng W, and AJ Szalai. Estrogen treatment abrogates neointima formation in human C-reactive protein transgenic mice. Arteriosclerosis, Thrombosis, and Vascular Biology, 2005; 25: 2094-2099   
AJ Szalai, X Hu, C Raman, SR Barnum. Requirement of the Fc receptor common -chain for  T cell-mediated promotion of murine experimental autoimmune encephalomyelitis. European Journal of Immunology, 2005, 35:3487-3492   
NHLBI Workshop Report. C-Reactive Protein: Basic and Clinical Research Needs. July 10-11, 2006. http://www.nhlbi.nih.gov/meetings/workshops/crp/report.htm   
FG Hage and AJ Szalai. C-reactive protein (CRP) gene polymorphisms, CRP blood levels, and cardiovascular disease risk. Journal of the American College of Cardiology. In Press, 2007   
Szalai AJ, GS Alarcon, J Calvo-Alen, SMA Toloza, MA McCrory, JC Edberg, G McGwin, Jr., HM Bastian, BJ Fessler, LM Vila, RP Kimberly, and JD Reveille. 2005. Systemic lupus erythematosus in a multiethnic US cohort (LUMINA) XXX: Association between C-reactive protein (CRP) gene polymorphism and vascular events. Rheumatology, 2005 in press    
Szalai AJ, Wu J, Lange EM, McCrory MA, Langefeld CD, Williams A, Zakharkin SO, George V, Allison DB, Cooper GS, Xie F, Fan Z, Edberg JC, Kimberly RP. 2005. Single nucleotide polymorphisms in the C-reactive protein (CRP) gene promoter that affect transcription factor binding, alter transcriptional activity, and associate with differences in baseline serum CRP level. Journal of Molecular Medicine, 2005 in press   
Kleeman R, L Verschuren, B-J de Rooij, J Lindeman, MM de Maat, AJ Szalai, HMG Princen, and T Kooistra. Evidence for anti-inflammatory activity of statins and PPARa activators in human C-reactive protein transgenic mice in vivo and in cultured human hepatocytes in vitro. Blood. In press, 2004    
Ren B, MA McCrory, C Pass, DC Bullard, Y Ma, DE Briles, and AJ Szalai. The virulence function of Streptococcus pneumonia surface protein A (PspA) involves inhibition of complement activation and impairment of complement receptor-mediated protection. The Journal of Immunology. In press, 2004   
Wang D, S Oparil, Y-F Chen, MA McCrory, and AJ Szalai. Neointima formation in response to carotid artery ligation is exaggerated in human C-reactive protein transgenic mice and prevented by estrogen treatment. Circulation, 110: 111-208, 2004   

Keywords
SLE, EAE, CRP, complement, innate immunity, FcgR, SAP, acute phase proteins, heart and blood vessel disease