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Malgorzata Simm

  • ASSISTANT PROFESSOR Medicine, Infectious Diseases
  • ASSISTANT PROFESSOR Pathology
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Education

  • Columbia University
    Virology

  • MSc, Poznan University of Medical Sciences
    Biochemistry

  • PhD, Children's Memorial Health Institute & AKM Institute of Hygiene and Epidemiology
    Molecular Biology

Biography

    Dr. Simm earned her PhD from Children’s Memorial Health Institute and AKM Institute of Hygiene and Epidemiology, Warsaw Poland. She completed her postdoctoral studies at Columbia University and following the receiving of NIH grants continued her association with the Department of Pathology and Cell Biology/Columbia University and St. Luke’s-Roosevelt Institute for Health Sciences until the end of 2013. In January of 2014 she joined the Icahn School of Medicine at Mount Sinai where she continues her studies.

    Dr. Simm’s research is focused on innate immunity response to pathogen invasion, emphasizing novel protein factors contributing to cellular resistance to HIV. She co-discovered and characterized the structure and function of a novel inhibitor of HIV LTR transcription – X-DING-CD4, a member of a newly characterized group of structurally and functionally conserved phosphatases found both in prokaryotic and eukaryotic cells. X-DING-CD4 was first characterized by her laboratory as a soluble HIV inhibitor secreted by HIV-resistant human cells and named HIV Resistance Factor (HRF). Subsequent collaborative research between her lab and three other groups (Department of Neuroscience, Temple University School of Medicine, Philadelphia, Université de la Méditerranée, France, and University of Auckland, New Zealand) determined that all DING proteins regardless of their cellular origin have highly conserved phosphate ion-binding domains and form a novel family of cellular enzymes. The X-DING-CD4 biology is quite unusual for a cellular enzyme because it was shown to carry out two distinct functions that can be distinguished by cellular localization: intracellular or endogenous, and secreted or exogenous. Endogenous DING is the enzymatically active form of the protein; it enters the nucleus and dephosphorylates NF-κB disrupting its binding to NF-κB-dependent promoters including the HIV LTR. Exogenous DING, on the other hand, appears to function as a signaling molecule that enters cells by macropinocytosis for paracrine-like induction of endogenous DING, thus expanding the NF-κB inhibitory effect of X-DING-CD4 throughout cell population. Except for HIV-1 elite controllers, human cells have generally low expression of X-DING-CD4 but it can be transiently induced in culture by treatment with the soluble protein form, Type I interferon (IFN) or by HIV infection, suggesting that similar as APOBEC-G3 and tetherin, the X-DING-CD4 functions as part of the innate immune responses to viral pathogens. In HIV-infected populations, cells from elite controllers, individuals with an innate ability to control HIV expression, had high constitutive levels of X-DING-CD4 mRNA whereas lymphocytes from people with progressing HIV disease tested in parallel had strikingly low X-DING RNA levels, suggesting a negative correlation between X-DING and HIV expression.

    Memberships:
    American Association for the Advancement of Science (Member since 1992).
    The Polish Institute of Arts & Sciences of America (Member since 2002).
    Columbia-Rockefeller Center for AIDS Research (Member since 2003).
    The Harvey Society (Member since 2006).

    Gene Bank Submissions:
    Accession FJ361193. Aaron, S., Ivanova, A., and Simm, M.: Cloning and sequencing of HIV-1Resistance Factor expressed by human CD4+T cells. GenBank: 10/08/2008.
    Accession HQ586056. Sachdeva, R., and Simm, M.: Identification of X-DING-CD4 mRNA from cells resistant to HIV utilizing linear polyacrylamide PCR amplification. GenBank: 12/18/2010.
    Accession HQ586056.2. X-DING-CD4 cDNA 1-879bp cDNA fragment. GenBank: 05/26/2013.

    Patents:
    PCT/US2013/050692; WO2014014918A3: X-DING-CD4 peptide. Sachdeva, R., and Simm, M. Published on 04/03/2014.

    Departmental and University Committees:
    St. Luke’s-Roosevelt Hospital Center Institutional Biosafety Committee (Member since 2007).

    Other:
    Editorial Board of Retrovirology Research and Treatment (Member since 2008).
    Editorial Board of Journal of AIDS and HIV Research (Member since 2010).
    Editorial Board of Journal of Proteomics (Member since 2011).
    Editorial Board of The Scientific World Journal (Member since 2011).

Publications

Simm M, Dzierzanowska D. [Detection of enterotoxic strains of Escherichia coli in children with diarrhea treated at the Child Health Center 1986-1988]. Medycyna doświadczalna i mikrobiologia 1991; 43(3-4).

Li G, Simm M, Potash MJ, Volsky DJ. Human immunodeficiency virus type 1 DNA synthesis, integration, and efficient viral replication in growth-arrested T cells. Journal of virology 1993 Jul; 67(7).

Huang ZB, Potash MJ, Simm M, Shahabuddin M, Chao W, Gendelman HE, Eden E, Volsky DJ. Infection of macrophages with lymphotropic human immunodeficiency virus type 1 can be arrested after viral DNA synthesis. Journal of virology 1993 Nov; 67(11).

Simm M, Shahabuddin M, Chao W, Allan JS, Volsky DJ. Aberrant Gag protein composition of a human immunodeficiency virus type 1 vif mutant produced in primary lymphocytes. Journal of virology 1995 Jul; 69(7).

Volsky DJ, Potash MJ, Simm M, Sova P, Ma XY, Chao W, Shahabuddin M. The human immunodeficiency virus type 1 vif gene: the road from an accessory to an essential role in human immunodeficiency virus type 1 replication. Current topics in microbiology and immunology 1995; 193.

Volsky DJ, Simm M, Shahabuddin M, Li G, Chao W, Potash MJ. Interference to human immunodeficiency virus type 1 infection in the absence of downmodulation of the principal virus receptor, CD4. Journal of virology 1996 Jun; 70(6).

Simm M, Chao W, Pekarskaya O, Sova P, Gupta P, Balachandran R, Volsky DJ. Genetic variability and function of the long terminal repeat from syncytium-inducing and non-syncytium-inducing human immunodeficiency virus type 1. AIDS research and human retroviruses 1996 Jun; 12(9).

Simm M, Pekarskaya O, Volsky DJ. Synthesis of full-length viral DNA in CD4-positive membrane vesicles exposed to HIV-1. A model for studies of early stages of the hiv-1 life cycle. The Journal of biological chemistry 1996 Nov; 271(45).

Kotler M, Simm M, Zhao YS, Sova P, Chao W, Ohnona SF, Roller R, Krachmarov C, Potash MJ, Volsky DJ. Human immunodeficiency virus type 1 (HIV-1) protein Vif inhibits the activity of HIV-1 protease in bacteria and in vitro. Journal of virology 1997 Aug; 71(8).

Simm M, Pekarskaya O, Potash MJ, Volsky DJ. Prolonged infection of peripheral blood lymphocytes by Vif-negative HIV type 1 induces resistance to productive HIV type 1 infection through soluble factors. AIDS research and human retroviruses 2000 Jul; 16(10).

Simm M, Su Z, Huang EY, Chen Y, Jiang H, Volsky DJ, Fisher PB. Cloning of differentially expressed genes in an HIV-1 resistant T cell clone by rapid subtraction hybridization, RaSH. Gene 2001 May; 269(1-2).

Simm M, Miller LS, Durkin HG, Allen M, Chao W, Lesner A, Potash MJ, Volsky DJ. Induction of secreted human immunodeficiency virus type 1 (HIV-1) resistance factors in CD4-positive T lymphocytes by attenuated HIV-1 infection. Virology 2002 Mar; 294(1).

Su ZZ, Chen Y, Kang DC, Chao W, Simm M, Volsky DJ, Fisher PB. Customized rapid subtraction hybridization (RaSH) gene microarrays identify overlapping expression changes in human fetal astrocytes resulting from human immunodeficiency virus-1 infection or tumor necrosis factor-alpha treatment. Gene 2003 Mar; 306.

Kartvelishvili A, Lesner A, Szponar M, Simm M. Microarray analysis of differentially expressed genes in cells resistant to HIV-1. Immunology letters 2004 Apr; 93(1).

McMahon JM, Simm M, Milano D, Clatts M. Detection of hepatitis C virus in the nasal secretions of an intranasal drug-user. Annals of clinical microbiology and antimicrobials 2004 May; 3.

Lesner A, Kartvelishvili A, Lesniak J, Nikolov D, Kartvelishvili M, Trillo-Pazos G, Zablotna E, Simm M. Monoubiquitinated histone H1B is required for antiviral protection in CD4(+)T cells resistant to HIV-1. Biochemistry 2004 Dec; 43(51).

Lesner A, Li Y, Nitkiewicz J, Li G, Kartvelishvili A, Kartvelishvili M, Simm M. A soluble factor secreted by an HIV-1-resistant cell line blocks transcription through inactivating the DNA-binding capacity of the NF-kappa B p65/p50 dimer. Journal of immunology (Baltimore, Md. : 1950) 2005 Aug; 175(4).

Li G, Aaron S, Kazmierczak K, Lesner A, Li Y, Ivanova A, Bentsman G, Potash MJ, Simm M. Inhibition of HIV-1 or bacterial activation of macrophages by products of HIV-1-resistant human cells. Immunology and cell biology; 85(8).

Simm M. The innate cellular responses to HIV-1 invasion: emerging molecules of ancient defense mechanisms. Archivum immunologiae et therapiae experimentalis; 55(3).

Aaron S, McMahon JM, Milano D, Torres L, Clatts M, Tortu S, Mildvan D, Simm M. Intranasal transmission of hepatitis C virus: virological and clinical evidence. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2008 Oct; 47(7).

Simm M. Counterpoint: Cord blood stem cell therapy for acquired immune deficiency syndrome. Stem cells and development; 18(1).

Li Y, Li G, Ivanova A, Aaron S, Simm M. The critical role of human transcriptional repressor CTCF mRNA up-regulation in the induction of anti-HIV-1 responses in CD4(+) T cells. Immunology letters 2008 Apr; 117(1).

Lesner A, Shilpi R, Ivanova A, Gawinowicz MA, Lesniak J, Nikolov D, Simm M. Identification of X-DING-CD4, a new member of human DING protein family that is secreted by HIV-1 resistant CD4(+) T cells and has anti-viral activity. Biochemical and biophysical research communications 2009 Nov; 389(2).

Sachdeva R, Simm M. Application of linear polyacrylamide coprecipitation of denatured templates for PCR amplification of ultra-rapidly reannealing DNA. BioTechniques 2011 Apr; 50(4).

Shilpi RY, Sachdeva R, Simm M. Cellular resistance to HIV-1 infection in target cells coincides with a rapid induction of X-DING-CD4 mRNA: indication of the unique host innate response to virus regulated through function of the X-DING-CD4 gene. Innate immunity 2012 Aug; 18(4).

Ivanova A, Shilpi RY, Sachdeva R, Li G, Simm M. Native X-DING-CD4 protein secreted by HIV-1 resistant CD4+ T cells blocks activity of IL-8 promoter in human endothelial cells infected with enteric bacteria. Innate immunity 2012 Aug; 18(4).

Sachdeva R, Darbinian N, Khalili K, Amini S, Gonzalez D, Djeghader A, Chabriére E, Suh A, Scott K, Simm M. DING proteins from phylogenetically different species share high degrees of sequence and structure homology and block transcription of HIV-1 LTR promoter. PloS one 2013; 8(8).

Sachdeva R, Shilpi RY, Simm M. The interplay between the X-DING-CD4, IFN-α and IL-8 gene activity in quiescent and mitogen- or HIV-1-exposed PBMCs from HIV-1 elite controllers, AIDS progressors and HIV-negative controls. Innate immunity 2014 Feb; 20(2).

Industry Relationships

Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.

Dr. Simm did not report having any of the following types of financial relationships with industry during 2013 and/or 2014: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.

Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.

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