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Salim Merali , PhD

Associate Professor, Biochemistry

Associate Professor, Fels Institute for Cancer Research and Molecular Biology

Director, Proteomics Research Facility

Telephone:  215-707-9228

Email: salim.merali@temple.edu

Fels Institute of Cancer Research And Molecular Biology

Department of Biochemistry

City University of New York

 

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Our laboratory focuses on identifying novel biochemical approaches to the treatment/diagnosis of Pneumocystis pneumonia (PCP) and cancer. PCP is associated with AIDS, malnourished infants and immunosuppressive drugs used for cancer, organ transplant and rheumatic diseases. Although we have explored many areas, including metabolism of folates, polyamines, and iron as well as culture, recently our emphasis has been on the metabolism of S-adenosylmethionine (AdoMet). An intersection between Pneumocystis and cancer research occurred as a result of a study of the relationship between plasma AdoMet and Pneumocystis pneumonia (PCP). We found PCP causes a drastic reduction in plasma AdoMet of experimental animals and became involved in a clinical investigation to determine whether this was also true in patients. We also found that AdoMet depletion does occur in human PCP; it is dramatic enough possibly to become the basis of a technique for minimally invasive diagnosis of this disease and for monitoring the response to therapy. In the course of the study we also discovered that cancer causes a remarkable increase in plasma AdoMet.

AdoMet is a critical biochemical intermediate serving both as the methyl donor for a myriad of biochemical events and as a precursor to the higher polyamines. Methylation is associated with control of protein and DNA function and polyamines are known to help condense and stabilize DNA and RNA. Thus defects in either methylation or polyamine metabolism can interfere with normal control of cell function and proliferation. The fact that AdoMet is highly elevated in the plasma of cancer patients perhaps reflects the lack of control of function and proliferation of cancerous tissue. One of our ongoing research projects is testing the hypothesis that plasma AdoMet can be used as a serological marker for the presence of cancer. We are analyzing plasma AdoMet of patients with various malignancies including those with GI, lung and breast cancers. The data we have already collected and other studies show that disturbed AdoMet metabolism is characteristic of malignancies; however, the mechanism behind the elevation of plasma AdoMet is unknown. We found an increase in the activity of AdoMet synthesizing enzyme in tumor tissue is involved but is not likely to be the whole story.

Biochemical and Molecular Properties of Pneumocystis

and Cancer as Basis for Diagnosis and Chemotherapy

Although we are involved in the investigation of AdoMet metabolism and cancer, our research in Pneumocystis continues. We have been able to find metabolic differences between host and Pneumocystis and now host and cancer cells. The expectation is that such differences are ripe areas for rational development of drugs as well as for developing an understanding of the pathology of these diseases. As our research has evolved, it became clear the tools and techniques we had developed earlier are now included with other tools and techniques to create a new fields of metabolomics and proteomics. We have turned fully in this new direction and have been able to equip the laboratory with capillary electrophoresis, MALDI TOF/TOF mass spectroscopy, nano liquid chromatography ion trap mass spectroscopy/mass spectroscopy, Ettan IPG phor system for two dimension electrophoresis, high pressure liquid chromatography, etc. We are applying those tools to create a better understanding of the role of AdoMet in Pneumocystis and cancer cells with the expectation that the data will lead to improved ways of treating/diagnosing PCP and cancer.

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Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

23806685. Perez-Leal O, Barrero CA, Merali S, Translational control of Nrf2 within the open reading frame. Biochem Biophys Res Commun :()2013 Jun 24

23701549. Perez-Leal O, Abou-Gharbia M, Gordon J, Childers WE, Merali S, A Novel Assay Platform for the Detection of Translation Modulators of Spermidine/Spermine Acetyltransferase. Curr Pharm Des :()2013 May 16

23139419. Steen HC, Nogusa S, Thapa RJ, Basagoudanavar SH, Gill AL, Merali S, Barrero CA, Balachandran S, Gamero AM, Identification of STAT2 serine 287 as a novel regulatory phosphorylation site in type I interferon-induced cellular responses. J Biol Chem 288:1(747-58)2013 Jan 4

23082855. Patel BB, Barrero CA, Braverman A, Kim PD, Jones KA, Chen DE, Bowler RP, Merali S, Kelsen SG, Yeung AT, Assessment of two immunodepletion methods: off-target effects and variations in immunodepletion efficiency may confound plasma proteomics. J Proteome Res 11:12(5947-58)2012 Dec 7

22354986. Perez-Leal O, Barrero CA, Clarkson AB, Casero RA Jr, Merali S, Polyamine-regulated translation of spermidine/spermine-N1-acetyltransferase. Mol Cell Biol 32:8(1453-67)2012 Apr

21811825. Perez-Leal O, Merali S, Regulation of polyamine metabolism by translational control. Amino Acids 42:2-3(611-7)2012 Feb

21642588. Perez-Leal O, Moncada C, Clarkson AB, Merali S, Pneumocystis S-adenosylmethionine transport: a potential drug target. Am J Respir Cell Mol Biol 45:6(1142-6)2011 Dec

21475143. Boden G, Song W, Duan X, Cheung P, Kresge K, Barrero C, Merali S, Infusion of glucose and lipids at physiological rates causes acute endoplasmic reticulum stress in rat liver. Obesity (Silver Spring) 19:7(1366-73)2011 Jul

21266224. Boden G, Merali S, Measurement of the increase in endoplasmic reticulum stress-related proteins and genes in adipose tissue of obese, insulin-resistant individuals. Methods Enzymol 489:(67-82)2011

20883044. Han Z, Liang CG, Cheng Y, Duan X, Zhong Z, Potireddy S, Moncada C, Merali S, Latham KE, Oocyte spindle proteomics analysis leading to rescue of chromosome congression defects in cloned embryos. J Proteome Res 9:11(6025-32)2010 Nov 5

20340163. Duan X, Kelsen SG, Clarkson AB Jr, Ji R, Merali S, SILAC analysis of oxidative stress-mediated proteins in human pneumocytes: new role for treacle. Proteomics 10:11(2165-74)2010 Jun

19408304. Terrasi M, Fiorio E, Mercanti A, Koda M, Moncada CA, Sulkowski S, Merali S, Russo A, Surmacz E, Functional analysis of the -2548G/A leptin gene polymorphism in breast cancer cells. Int J Cancer 125:5(1038-44)2009 Sep 1

18817430. Duan X, Kelsen SG, Merali S, Proteomic analysis of oxidative stress-responsive proteins in human pneumocytes: insight into the regulation of DJ-1 expression. J Proteome Res 7:11(4955-61)2008 Nov

18567819. Boden G, Duan X, Homko C, Molina EJ, Song W, Perez O, Cheung P, Merali S, Increase in endoplasmic reticulum stress-related proteins and genes in adipose tissue of obese, insulin-resistant individuals. Diabetes 57:9(2438-44)2008 Sep

18180293. Moncada CA, Clarkson A, Perez-Leal O, Merali S, Mechanism and tissue specificity of nicotine-mediated lung S-adenosylmethionine reduction. J Biol Chem 283:12(7690-6)2008 Mar 21

18079489. Kelsen SG, Duan X, Ji R, Perez O, Liu C, Merali S, Cigarette smoke induces an unfolded protein response in the human lung: a proteomic approach. Am J Respir Cell Mol Biol 38:5(541-50)2008 May

17934114. Greenberg AK, Rimal B, Felner K, Zafar S, Hung J, Eylers E, Phalan B, Zhang M, Goldberg JD, Crawford B, Rom WN, Naidich D, Merali S, S-adenosylmethionine as a biomarker for the early detection of lung cancer. Chest 132:4(1247-52)2007 Oct

15668255. Shivji M, Burger S, Moncada CA, Clarkson AB Jr, Merali S, Effect of nicotine on lung S-adenosylmethionine and development of Pneumocystis pneumonia. J Biol Chem 280:15(15219-28)2005 Apr 15

15321660. Merali S, Clarkson AB Jr, S-adenosylmethionine and Pneumocystis. FEMS Microbiol Lett 237:2(179-86)2004 Aug 15

12699956. Skelly M, Hoffman J, Fabbri M, Holzman RS, Clarkson AB Jr, Merali S, S-adenosylmethionine concentrations in diagnosis of Pneumocystis carinii pneumonia. Lancet 361:9365(1267-8)2003 Apr 12

11779874. Coppi A, Merali S, Eichinger D, The enteric parasite Entamoeba uses an autocrine catecholamine system during differentiation into the infectious cyst stage. J Biol Chem 277:10(8083-90)2002 Mar 8

11709340. Clarkson AB Jr, Turkel-Parrella D, Williams JH, Chen LC, Gordon T, Merali S, Action of deferoxamine against Pneumocystis carinii. Antimicrob Agents Chemother 45:12(3560-5)2001 Dec

11565084. Hagmann S, Merali S, Sitnitskaya Y, Fefferman N, Pollack H, Pneumocystis carinii infection presenting as an intra-abdominal cystic mass in a child with acquired immunodeficiency syndrome. Clin Infect Dis 33:8(1424-6)2001 Oct 15

10809741. Merali S, Vargas D, Franklin M, Clarkson AB Jr, S-adenosylmethionine and Pneumocystis carinii. J Biol Chem 275:20(14958-63)2000 May 19

10639359. Merali S, Saric M, Chin K, Clarkson AB Jr, Effect of a bis-benzyl polyamine analogue on Pneumocystis carinii. Antimicrob Agents Chemother 44:2(337-43)2000 Feb

10409651. Merali S, Pneumocystis carinii polyamine catabolism. J Biol Chem 274:30(21017-22)1999 Jul 23

10051654. Merali S, Frevert U, Williams JH, Chin K, Bryan R, Clarkson AB Jr, Continuous axenic cultivation of Pneumocystis carinii. Proc Natl Acad Sci U S A 96:5(2402-7)1999 Mar 2

8891137. Chin K, Merali S, Saric M, Clarkson AB Jr, Continuous infusion of DL-alpha-difluoromethylornithine and improved efficacy against a rat model of Pneumocystis carinii pneumonia. Antimicrob Agents Chemother 40:10(2318-20)1996 Oct

8723489. Merali S, Chin K, Grady RW, Clarkson AB Jr, Trophozoite elimination in a rat model of Pneumocystis carinii pneumonia by clinically achievable plasma deferoxamine concentrations. Antimicrob Agents Chemother 40:5(1298-300)1996 May

8849262. Merali S, Clarkson AB Jr, Polyamine content of Pneumocystis carinii and response to the ornithine decarboxylase inhibitor DL-alpha-difluoromethylornithine. Antimicrob Agents Chemother 40:4(973-8)1996 Apr

8852721. Merali S, Clarkson AB Jr, Polyamine analysis using N-hydroxysuccinimidyl-6-aminoquinoyl carbamate for pre-column derivatization. J Chromatogr B Biomed Appl 675:2(321-6)1996 Jan 26

8540710. Merali S, Chin K, Del Angel L, Grady RW, Armstrong M, Clarkson AB Jr, Clinically achievable plasma deferoxamine concentrations are therapeutic in a rat model of Pneumocystis carinii pneumonia. Antimicrob Agents Chemother 39:9(2023-6)1995 Sep

7492082. Merali S, Chin K, Grady RW, Weissberger L, Clarkson AB Jr, Response of rat model of Pneumocystis carinii pneumonia to continuous infusion of deferoxamine. Antimicrob Agents Chemother 39:7(1442-4)1995 Jul

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