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Marion Chan, PhD
Associate Professor, Microbiology and Immunology
Department of Microbiology and Immunology
Temple Autoimmunity Center
Cornell University Medical College, PhD
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Dr. Marion Chan’s laboratory is interested in understanding mechanisms that resolve inflammation. She and her team have developed two model systems in mice which, in combination, allows study of these mechanism at the cellular and the whole organism levels. This work has implications for a wide spectrum of disease states, which is now thought to involve a chronic neuroinflammatory response.
Chan’s laboratory was the first to show that there is an active mechanism of resolution underlying remission and relapse in murine collagen-induced arthritis (CIA), a well-accepted model of rheumatoid arthritis in humans. Her findings indicated that COX inhibitors will interfere with the resolution process, resulting in chronic inflammation. (This is a critical issue because COX-2 inhibitors are widely used for treating many inflammatory diseases.) Her current work centers on elucidating the details of this mechanism. The immediate focus is on the eicosanoids synthesized from arachidonic acid through the COX and lipoxygenase (LOX) pathways. Many of these bioactive lipids are ligands for peroxisome proliferator-activated receptor (PPAR), a group of nuclear factors that serve as targets for diabetes, obesity, vascular disease, and other inflammatory diseases. One of the characteristics of PPARγ is that it primes monocytes to differentiate into alternatively activated M2 phenotype. This subclass of macrophages expresses scavenger receptors for apoptotic cells, produces transforming growth factor β and IL-10, and has been ascribed vital roles in the clearance of apoptotic neutrophils and wound repair. They are likely the initiators of resolution, in contrast to the classically activated macrophages (M1) that induce inflammation.
The second murine model of inflammation looks at leishmaniasis, a parasitic infection that produces inflammation and affects 12 million people worldwide. The etiological agent is a parasitic protozoan that infects the bone marrow, liver, skin, and spleen of susceptible individuals chronically. The parasite lives and replicates within macrophages. The Chan group is investigating whether the parasite harnesses resolution mechanisms to maintain the life-long infection. The hypothesis is that, upon infection, Leishmania polarizes macrophages towards the alternatively activated M2 phenotype that produce arginase, instead of the classically activated M1 macrophages that express inducible nitric oxide synthase. Consequently, arginine, the common substrate of the two enzymes, diverge from producing the parasiticidal nitric oxide. Among the dietary compounds studied in the laboratory, curcumin is a PPARγ activator and agonist. This anti-inflammatory molecule increases parasite burden in Leishmania donovani-infected mice.
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Chan MM, Huang HI, Mattiacci JA, Fong D. Modulation of cytokine gene expression by curcumin. In "Food Factors in Health Promotion and Disease Prevention", ed. Shahidi F, Ho C-T, Watanabe S, Osawa T. American Chemical Society Press, Washington D.C., pp. 86-99, 2003.
Chan MM, Fong D. Modulation of the nitric oxide pathway by natural products. In Nitric Oxide in Inflammation and Tissue Injury (Laskin J, Laskin D, eds.). Marcel Dekker, Inc., New York, NY, 1999.
Chan MM. Inhibition of tumor necrosis factor by curcumin, a phytochemical. Biochem Pharmacol. 1995 May 26;49(11):1551-6.
Chan MM, Fong D. 1994. Anti-inflammatory and cancer preventive immuno-modulation through the diet: The effects of curcumin on T lymphocytes. In "Food Phytochemicals for Cancer Prevention", ed. Huang M-T, Ho C-T, American Chemical Society Press, Washington D.C., pp. 222-230.
Chan MM, Fong D. Plant microtubule inhibitors against trypanosomatids. Parasitol Today. 1994 Nov;10(11):448-51.
Chan MM, Grogl M, Chen CC, Bienen EJ, Fong D. Herbicides to curb human parasitic infections: in vitro and in vivo effects of trifluralin on the trypanosomatid protozoans. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5657-61.
Chan MM. T cell response in murine Leishmania mexicana amazonensis infection: production of interferon-gamma by CD8+ cells. Eur J Immunol. 1993 May;23(5):1181-4.
Chan MM, Fong D. Inhibition of leishmanias but not host macrophages by the antitubulin herbicide trifluralin. Science. 1990 Aug 24;249(4971):924-6.
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Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)
22536211. Chan MM, Fong D, The Interplay of PPARs with Parasites and Related Intracellular Pathogens. PPAR Res 2012:(624845)2012
22448168. Chan MM, Adapala N, Chen C, Peroxisome Proliferator-Activated Receptor-?-Mediated Polarization of Macrophages in Leishmania Infection. PPAR Res 2012:(796235)2012
20435922. Chan MM, Moore AR, Resolution of inflammation in murine autoimmune arthritis is disrupted by cyclooxygenase-2 inhibition and restored by prostaglandin E2-mediated lipoxin A4 production. J Immunol 184:11(6418-26)2010 Jun 1
20169106. Chan MM, Evans KW, Moore AR, Fong D, Peroxisome proliferator-activated receptor (PPAR): balance for survival in parasitic infections. J Biomed Biotechnol 2010:(828951)2010
18794851. Adapala N, Chan MM, Long-term use of an antiinflammatory, curcumin, suppressed type 1 immunity and exacerbated visceral leishmaniasis in a chronic experimental model. Lab Invest 88:12(1329-39)2008 Dec
16402374. Chan MM, Soprano KJ, Weinstein K, Fong D, Epigallocatechin-3-gallate delivers hydrogen peroxide to induce death of ovarian cancer cells and enhances their cisplatin susceptibility. J Cell Physiol 207:2(389-96)2006 May
15772867. Chan MM, Adapala NS, Fong D, Curcumin overcomes the inhibitory effect of nitric oxide on Leishmania. Parasitol Res 96:1(49-56)2005 Apr
12632163. Chan MM, Bulinski JC, Chang KP, Fong D, A microplate assay for Leishmania amazonensis promastigotes expressing multimeric green fluorescent protein. Parasitol Res 89:4(266-71)2003 Mar
12447990. Chan MM, Fong D, Soprano KJ, Holmes WF, Heverling H, Inhibition of growth and sensitization to cisplatin-mediated killing of ovarian cancer cells by polyphenolic chemopreventive agents. J Cell Physiol 194:1(63-70)2003 Jan
11841782. Chan MM, Antimicrobial effect of resveratrol on dermatophytes and bacterial pathogens of the skin. Biochem Pharmacol 63:2(99-104)2002 Jan 15
11020457. Chan MM, Mattiacci JA, Hwang HS, Shah A, Fong D, Synergy between ethanol and grape polyphenols, quercetin, and resveratrol, in the inhibition of the inducible nitric oxide synthase pathway. Biochem Pharmacol 60:10(1539-48)2000 Nov 15
9714315. Chan MM, Huang HI, Fenton MR, Fong D, In vivo inhibition of nitric oxide synthase gene expression by curcumin, a cancer preventive natural product with anti-inflammatory properties. Biochem Pharmacol 55:12(1955-62)1998 Jun 15
9393670. Chan MM, Fong D, Ho CT, Huang HI, Inhibition of inducible nitric oxide synthase gene expression and enzyme activity by epigallocatechin gallate, a natural product from green tea. Biochem Pharmacol 54:12(1281-6)1997 Dec 15
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Current or Recent Grant Support of Active Projects:
Marion M. Chan, PhD as Principal Investigator:
National Institutes of Health, R01 AI44445
Nitric Oxide Inhibitor and Leishmania Pathogenesis
National Institutes of Health, R21
Counter Balance in Inflammation
American Institute for Cancer Research
Epigallocatechin-3-gallate for Enhancement of Cisplatin Therapy
Center for Advanced Food Technology, Rutgers University
Modulation of Gene Expression of Inflammation Mediators by Food
Marion M. Chan, PhD as Co-Investigator:
National Institutes of Health, T32 A107101, C. D. Platsoucas, PhD, Principal Investigator/Program Director; Microbiology and Immunology Training Program
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