Malgorzata Simm

Malgorzata Simm, PhD

  • ADJUNCT ASSISTANT PROFESSOR | Medicine, Infectious Diseases

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).

Education

MSc, Poznan University of Medical Sciences

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

Columbia University