The University of Toledo

Salah-uddin Ahmed

 

Salah-uddin Ahmed Assistant Professor Department of Pharmacology 419.383.1913 office 419.383.1909 FAX HEB 282F

Institutions/Degrees

B.S.	Rajasthan University, Jaipur, India Zoology and Chemistry
M.S.	Jamia Hamdard University, New Delhi, India Toxicology
Ph.D.	Jamia Hamdard University, New Delhi, India
Post-Doc	Case Western Reserve University, Cleveland, OH Fellow Orthopedics

 

Research Interests

My primary research interest is to test the efficacy of green tea and its active compound epigallocatechin gallate (EGCG) in rheumatoid arthritis (RA). Using synovial fibroblasts isolated from human RA joints, we are studying the mechanism of green tea and EGCG mediated regulation of chemokine production and chemokine receptor expression, and inhibition of synovial fibroblast invasion. Furthermore, we are also testing the therapeutic potential of EGCG in regulating cell recruitment, angiogenesis and joint destruction in animal models of RA and in RA synovial tissue (ST)-severe combined immunodeficient (SCID) chimera by blocking chemokine receptor CCR1/CCR5 expression. Patients suffering from RA tend to develop cardiovascular complications. My research focus in this area is to study the role of pro-inflammatory cytokines and downstream inflammatory mediators in the manifestation of cardiovascular complications in RA. Based on these findings, we plan to test potential novel anti-inflammatory molecules in clinical intervention studies. The success of these studies may lead to a significant advancement in the development of EGCG or structurally related molecules as potential treatment options for RA and possibly other autoimmune diseases.

 

Academic/Clinical Appointments

4/2000-1/2001	Associate Research Scientist, Department of Pharmacology, R&D Centre of Zydus Cadila, Ahmedabad, India
01/2003-05/2005	Research Associate, Department of Medicine, Division of Rheumatic Diseases, Case Western Reserve University, Cleveland, OH
05/2005-08/200	Research Investigator, Department of Internal Medicine/Division of Rheumatology, University of Michigan, Ann Arbor, MI
09/2008-06/2009	Research Assistant Professor, Department of Internal MedicineDivision of Rheumatology, University of Michigan, Ann Arbor, MI

 

Honors and Awards

1997-1998	Junior Research Fellowship, Council of Scientific and Industrial Research, New Delhi, India
1998-1999	Doctoral Fellowship for Meritorious Students in Research, Hamdard National Foundation, India
1999	Young Scientist Travel Fellowship, InternationalUnion of Pharmacology
2007	Young Scientist Travel Award, American Society for Pharmacology and Experimental Therapeutics
2012	ACR/REF-Abbott Health Professional Graduate Preceptorship Award, American College of Rheumatology

 

Bibliography (selected publications out of 39)

 

Rahman A, Ahmed S, Khan N, Sultana S, Athar M. Glyceryl trinitrate, a nitric oxide donor, suppresses renal oxidant damage caused by potassium bromate. Redox Rep 1999;4(6):263-269.

Ahmed S, Rahman A, Saleem M, Athar M, Sultana S. Ellagic acid ameliorates nickel induced biochemical alterations: diminution of oxidative stress. Hum Exp Toxicol1999;18(11):691-698.

Ahmed S, Rahman A, Alam A, Saleem M, Athar M, Sultana S. Evaluation of the efficacy of Lawsonia alba in the alleviation of carbon tetrachloride-induced oxidative stress. J Ethnopharmacol 2000;69(2):157-164.

Ahmed S, Rahman A, Mathur M, Athar M, Sultana S. Anti-tumor promoting activity of Asteracantha longifolia against experimental hepatocarcinogenesis in rats. Food Chem Toxicol 2001;39(1):19-28.

Ahmed S, Rahman A, Hasnain A, Lalonde M, Goldberg VM, Haqqi TM. Green tea polyphenol epigallocatechin-3-gallate inhibits the IL-1β-induced activity and expression of cyclooxygenase-2 and nitric oxide synthase-2 in human chondrocytes. Free Radic Biol Med 2002;33(8):1097-1105.

Singh R^§, Ahmed S^§, Islam N, Goldberg VM, Haqqi TM. Epigallocatechin-3-gallate inhibits interleukin-1β-induced expression of nitric oxide synthase and production of nitric oxide in human chondrocytes: suppression of nuclear factor κB activation by degradation of the inhibitor of nuclear factor κB. Arthritis Rheum 2002;46(8):2079-2086. [^§Equal contribution].

Singh R, Ahmed S, Malemud CJ, Goldberg VM, Haqqi TM. Epigallocatechin-3-gallate selectively inhibits interleukin-1β-induced activation of mitogen activated protein kinase subgroup c-Jun N-terminal kinase in human osteoarthritis chondrocytes. J Orthop Res 2003;21(1):102-109.

Ahmed S, Rahman A, Hasnain A, Goldberg VM, Haqqi TM. Phenyl N-tert-butylnitrone down-regulates interleukin-1β-stimulated matrix metalloproteinase-13 gene expression in human chondrocytes: suppression of c-Jun NH2-terminal kinase, p38-mitogen-activated protein kinase and activating protein-1. J Pharmacol Exp Ther 2003;305(3):981-988.

Rahman A, Ahmed S, Vasenwala SM, Athar M. Glyceryl trinitrate, a nitric oxide donor, abrogates ferric nitrilotriacetate-induced oxidative stress and renal damage. Arch Biochem Biophys 2003;418(1):71-79.

Ahmed S, Wang N, Lalonde M, Goldberg VM, Haqqi TM. Green tea polyphenol epigallocatechin-3-gallate (EGCG) differentially inhibits interleukin-1β-  induced expression of matrix metalloproteinase-1 and -13 in human chondrocytes. J Pharmacol Exp Ther 2004;308(2):767-773.

Wang N, Ahmed S, Haqqi TM. Genomic structure and functional characterization of the promoter region of human IκB kinase-related kinase IKK-i/IKKε gene. Gene2005;353(1):118-133.

Ahmed S, Wang N, Hafeez BB, Cheruvu V, Haqqi TM. Punica granatum L extract inhibits IL-1β-induced expression of matrix metalloproteinases in human chondrocytes by inhibiting the activation of mitogen-activated protein kinases sub-groups p38-MAPK and JNK and the nuclear Factor-κB Activity. J Nutr2005;135(9):2096-2102.

Ahmed S, Malemud CJ, Haqqi TM. Biological basis for the role of botanicals in arthritis. Evid Based Complement Alternat Med2005;2(3):301-308.

Hafeez BB, Ahmed S, Wang N, Gupta S, Haqqi TM. Green tea induces apoptosis in SAOS-2 cells via inhibition of nuclear factor-κB (NF-κB) and activation of caspase-3. Toxicol Appl Pharmacol2006;216:11-19.

Ahmed S*, Pakozdi A, Koch AE. Regulation of interleukin-1β-induced chemokine production and matrix metalloproteinase-2 (MMP-2) activation by epigallocatechin-3-gallate (EGCG) in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum 2006;54(8):2393-2401. [* Corresponding author].

Amin MA, Mansfield PJ, Pakozdi A, Campbell PL, Ahmed S, Martinez RJ, Koch AE. Interleukin-18 induces angiogenic factors in rheumatoid arthritis synovial tissue fibroblasts via distinct signaling pathways. Arthritis Rheum2007;56(6):1787-1797.

Haas CS, Amin MA, Ruth JH, Allen BB, Ahmed S, Pakozdi A, Woods JM, Shahrara S, Koch AE. In vivo inhibition of angiogenesis by interleukin-13 gene therapy in a rat model of rheumatoid arthritis. Arthritis Rheum2007;56(8):2535-2548.

Ahmed S*, Hubert M, Kwan K, Ruth JH, Campbell PJ, Rabquer BJ, Pakozdi A, Koch AE. Epigallocatechin-3-gallate inhibits IL-6 synthesis and suppresses transsignaling by enhancing soluble gp130 production. Proc Natl Acad Sci USA 2008;105:14692-14697. [*Corresponding author].

Ahmed S*, Silverman MD, Hubert M, Kwan K, Matuszczak N, Koch AE. Down-regulation of Mcl-1 by epigallocatechin-3-gallate (EGCG) sensitizes rheumatoid arthritis synovial fibroblasts to tumor necrosis factor-alpha (TNF-a)-induced apoptosis. Arthritis Rheum. 60:1282-1293, 2009. [* Corresponding author].

Ahmed S. Biological evidence for the benefit of green tea and EGCG in arthritis. Curr. Rheum. Rev.5: 259-265, 2009.

Marotte H, Ruth JH, Campbell PJ, Koch AE, Ahmed S. Green tea extract inhibits chemokine production, but upregulates chemokine receptor expression, in rheumatoid arthritis synovial fibroblasts and rat adjuvant-induced arthritis. Rheumatology49; 467-479, 2010.

Marotte H, Ahmed S, Ruth JH, Koch AE. Blocking ERK1/2 reduces TNF-α-induced IL-18 bioactivity in rheumatoid arthritis synovial fibroblasts by induction of IL-18BPa. Arthritis Rheum62:722-731, 2010.

Ahmed S. Emerging role of green tea polyphenol EGCG in rheumatic diseases. Arthritis Res Therap12: 208, 2010.

Ruth JH, Arendt MD, Amin MA, Ahmed S, Marotte H, Rabquer BJ, Lesch C, Lee SH, Koch AE. Expression and Function of CXCL16 in a Novel Model of Gout. Arthritis Rheum62(8):2536-44, 2010.

Jones BA, Beamer M, Ahmed S. Fractalkine/CX3CL1: a potential new target for inflammatory diseases. Mol Interv2010: 10(5); 263-270.

Jones BA, Koch AE, and Ahmed S. Pathological role of Fractalkine/CX3CL1 in rheumatic diseases. Front Immunol2:82, 2011 (Epub).

Other Media

 Article entitled “Ahmed S, Wang N, Haqqi TM. Punica granatum L extract inhibits IL-1β-induced expression of matrix metalloproteinases in human chondrocytes by inhibiting the activation of mitogen-activated protein kinases sub-groups p38-MAPK and JNK and the nuclear Factor-κB Activity. J Nutr 2005;135(9):2096-2102” was published in CBS online with the weblink: http://www.cbsnews.com/stories/2005/09/09/health/webmd/ main830305.shtml and covered by NIAMS 2005 research highlights.

Abstract entitled “Epigallocatechin-3-gallate (EGCG) inhibits IL-1β-induced IL-6 production and cyclooxygenase-2 (COX-2) expression in rheumatoid arthritis synovial fibroblasts in vitro” was selected by the American Society of Nutrition for their news release at the Experimental Biology 2007 meeting, Washington, D.C.The same article was covered in the news release of CBS onlinehttp://www.cbsnews.com/stories/2007/04/30/health/webmd/main2743971.shtml?source=RSSattr=Health_2743971], Washington Post online [http://www.washingtonpost.com/wp-dyn/content/article/2007/04/30/AR2007043000418.html], ABC News online [http://abcnews.go.com/Health/Healthday/story?id=4506757&page=1], and on the UMHS website [http://www.med.umich.edu/opm/newspage/2007/greentea.htm.

Research cited at the Universityof Toledo Research News: “Researcher looking for rheumatoid arthritis treatment in tea cup”: UT News; March 15, 2009, Vol. 10, Issue 27; page 5.

Expert comments in the Health News section of Better Homes and Gardens magazine: January 2010 edition page 128.

Research cited at the WGTE Toledo Plugg-In Medicine Program: “A Joint Solution: How Green Tea can diminish the effects of Rheumatoid Arthritis”: February, 2011.

Research cited at the University of Toledo Research News: “Researcher recognized for proposed treatment for inflammatory diseases”: UT News; March 7, 2011.

 

Book Chapters

Ahmed S., Haqqi TM. Emerging role of green tea in prevention of arthritis. In: Tea and Human Health (Weisberg J, Siddiqi M, eds.).Cambridge,Mass.: CABI Publishing, pp 172-181, 2006.