Associate researcher CONICET/Assistant professor UNC
Phone: +54 351 5353855 x 3416
Glycosphingolipid-dependent modulation of Interferon alpha receptor activity in melanoma
Melanoma, a malignant skin cancer affecting thousands of people worldwide, is the leading cause of death from skin disease. Ulceration of melanoma lesions is associated to a poor prognosis but, paradoxically, ulcerated melanomas show a better response to interferon-alpha (IFN-a) therapy than non-ulcerated melanomas. By analyzing a publicly available gene expression microarray dataset of melanoma lesions, we found ulcerated melanomas have increased expression of two glycosyltransferases participating in synthesis of globotriaosylceramide (Gb3) and galabiosylceramide (Gb2). Both carrying a terminal Gal-alpha 1,4-Gal epitope, these two glycosphingolipids were reported to modulate IFN-a receptor (IFN?) activity on a lymphoma cell line. Based on this background and preliminary data, and using different in silico, in vitro and in vivo approaches, we aim to address the following goals: 1) to investigate how changes in Gb3 levels influence the activation of IFNAR. 2) To investigate the influence of variations of Gb3 levels on the in vivo response to IFN-a therapy in a subcutaneous melanoma model.
- “Mycobacterium bovis Bacillus Calmette-Guérin (BCG) Alters Melanoma Microenvironment Favoring Antitumor T Cell Responses and Improving M2 Macrophage Function”. “RD Lardone *, A Chan, BY Lee, LJ Foshag, MB Faries, PA Sieling, DJ Lee*. Front Immunol 2017, 8:965 (*: co-corresponding author)
- “Cross-platform comparison of independent datasets identifies an immune signature associated with improved survival in metastatic melanoma”. RD Lardone *, S Plaisier, MS Navarrete, J Shamonki, PA Sieling, DJ Lee*. Oncotarget 2016, 7(12):14415 (*: co-corresponding author)
- “Individual restriction of fine specificity variability in anti-GM1 IgG antibodies associated with Guillain-Barré syndrome”. RD Lardone *, N Yuki, FJ Irazoqui, GA Nores. Sci Rep 2016, 6:19901. (*: corresponding author)
- “Immune response modulation by tumor-secreted glycosphingolipids”. RD Lardone, I Cely, PA Sieling, DJ Lee. J Glycobiol 2014; 3(1).
- “Anti-GM1 IgG antibodies in Guillain-Barré syndrome: fine specificity is associated with disease severity”. RD Lardone, N Yuki, M Odaka, JL Daniotti, FJ Irazoqui, GA Nores. J Neurol Neurosurg Psychiatry. 2010; 81(6):629-33.
2000-Licensed Clinical Biochemistry (equivalent to B.Sc. in Clinical Biochemistry). School of Chemistry, Universidad Nacional de Córdoba, Córdoba, Argentina.
2007-Doctor in Chemistry (equivalent to PhD in Chemistry). School of Chemistry, Universidad Nacional de Córdoba, Córdoba, Argentina. Thesis title: “Characterization of neuropathy-associated anti-glycosphingolipid antibodies”. Advisor: Prof. Dr. Gustavo A. Nores.”
1998-2000: Pre-graduated student. Advisor: Dr. Gustavo Nores. Department of Biological Chemistry, Universidad Nacional de Córdoba. Topic: “Anti-GM1 IgM antibodies in neuropathies”.
2001-2007: Research Fellow. Advisor: Dr. Gustavo A. Nores. Department of Biological Chemistry, Universidad Nacional de Córdoba. Topic: “A glycobiology approach to the immune response to glycans”.
2007-2009: Postdoctoral Research Fellow. Advisor: Dr. Gustavo A. Nores. Department of Biological Chemistry, Universidad Nacional de Córdoba. Topic: “Structural studies on glycan-antibody interactions in an animal model of Guillain-Barré syndrome”.
2009-2011: Postdoctoral Associate. Advisor: Dr. Jamey D. Marth. Center for Nanomedicine, Sanford Burnham Medical Research Institute at UCSB, Saint Barbara, CA. Topic: “Prevention of autoimmune disease induction in a mouse model of alpha-Mannosidase II deficiency”.
2011-2016: Postdoctoral Fellow. Advisor: Dr. Delphine J. Lee. Department of Translational Immunology, John Wayne Cancer Institute at Saint John’s Health Center. Topics: “Bioinformatics approaches to study beneficial immune response in melanoma” and “BCG-induced reprogramming events to improve antitumor immunity in melanoma”.
2017-current: Associate Researcher (CIC is UNLU), Department of Biological Chemistry, School of Chemistry, UNC and CIQUIBIC (Conicet)
1997: Undergraduate Teaching Assistant. Department of Physical Chemistry, School of Chemistry, UNC. Collaborated on Lab Practice Work teaching for “Laboratory I”.
1998-2001: Undergraduate Teaching Assistant. Department of Biological Chemistry, School of Chemistry, UNC. Collaborated on Lab Practice Work teaching for “Laboratory IV”.
2001-2009: Instructor. Department of Biological Chemistry, School of Chemistry, UNC. Teaching Lab Practice Work for “Biophysical Chemistry” and “Pathological Biochemistry”.
2017-current: Assistant Professor. Department of Biological Chemistry, School of Chemistry, U.N.C. Teaching Seminars for “Biotechnology” and “General Biochemistry”; teaching lectures for “Pathological Biochemistry”.”
Institutional Management Background
2006-2008 Council Member of the "Department of Biological Chemistry" Departmental Council (School of Chemistry, Universidad Nacional de Córdoba).
2015-2016 Research Study Coordinator of Alpha IRB-approved study: “Collection of peripheral blood and tissue from cancer patients to investigate mechanisms of BCG-stimulated innate and adaptive immunity”. PI: Dr. Delphine Lee. Co-investigators: Dr. Leland Foshag, Dr. Mark Faries. Sponsor: John Wayne Cancer Institute. Protocol Number: BCG_J001.”
Background on Science outreach and extension
PATENT: Lardone RD, Plaisier SB, Sieling PA, Lee DJ (Inventors). Title: “Gene expression signatures for predicting survival in metastatic melanoma”. United States Patent and Trademark Office (USPTO). Provisional application #62157900, 2015″.