Gabriel A. Rabinovich

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Gabriel A. Rabinovich is an Argentine biochemist who is currently a professor at the School of Exact and Natural Sciences at the University of Buenos Aires. He is also the deputy director of Immunopathology Laboratories, and the head of Structural and Functional Glycomic Laboratories.

Contents

Rabinovich has conducted research on effective tumor immunotherapy. He looked at different ways in which tumors overcome immune responses and how such tumors can be regressed. [1] He also looked at the properties of galectins, and how they show potential for disease. [2]

Early life

Rabinovich was born in Córdoba, Argentina in 1969. He graduated from the School of Chemical Sciences at National University of Córdoba in 1993 with a Biochemistry degree. He then earned a Ph.D. in Immunology while at the same university in 1999. [3]

After graduating, Rabinovich obtained a post-doctoral position at the University of Buenos Aires. He is also a member of the Argentine National Academy of Science, was a visiting professor at multiple universities, and is on 12 different journal Editorial Boards. He is now a full-time professor of Immunology and a senior investigator with the National Research Council. [3]

Research and current work

Rabinovich has published over 200 articles which have received more than 12,000 citations. His work alongside his colleagues at the Laboratory of Immunopathology and Glycomedicine involves galectins and their immunoregulatory functions. They found that galectin-glycan interactions are crucial to immune response to reduce inflammation while also preventing autoimmunity and promoting immune. [3]

In 1999, Rabinovich and his colleagues looked at the therapeutic effects of GAL-1 and the mechanisms it uses in a collagen-induced arthritis model. They administered recombinant GAL-1 daily and found it to lead in reduction of anticollagin immunoglobin levels. They also found GAL-1 to inhibit proinflammatory response, and that there is a correlation between the apoptotic properties in vitro with the immunomodulatory properties in vivo. They concluded that this could lead to a therapeutic treatment of helper T cell type 1-mediated autoimmune disorders. [4]

In 2002, Rabinovich worked alongside other scientists to look further into galectins and their ligands. They found that some members of the galectin family inhibited the inflammatory response while others enhanced it. Their research showed that galectins work to regulate cell signaling, growth, secretions, and other interactions which affect the inflammatory response to tumor progression. [5]

In 2004, Rabinovich and his colleagues further researched the galectin-1 gene and found that if this gene is inhibited in vivo, it promotes tumor rejection while stimulating tumor-specific T cell responses. They concluded that this finding could be used in cancer immunotherapy by promoting the response of these tumor-specific T cells. [6]

In 2007, Rabinovich and his colleagues made progress toward development of drugs for thrombosis, inflammation, and tumor progression. They did this through a comparative study in which they obtained fucoidans from brown algae and looked at the responses to leucocytes, thrombin, coagulants, and carcinoma cells. [7]

In 2008, Robinovich found that glycan contains information that is prevalent in the development of cancer and autoimmune diseases. Glycosylation is important for recognizing pathogens but also for controlling immune homeostasis and modulating immune response. [8] In 2018, he continued to look at galectin-driven regulation and how galectin-glycan interactions play a role in autoimmune inflammation. [9]

In 2019, Rabinovich worked with his colleagues to study Gal-12 and found that it promoted angiogenesis in vitro by influencing endothelial cells. They also found that adipose tissue homeostasis could be controlled by controlling endothelial cells through glycosylation-dependent pathways. Under hypoxic conditions, the regulation of this gene increased, and Gal-12 plays an important role in adipose tissue for both differentiation and homeostasis. [10]

As of March 2020, Rabinovich and his colleagues published a patent for their invention of kits and methods which use galectin-1 to diagnose, monitor, treat, and modulate lymphoproliferate disorders and angiogenesis disorders associated with hypoxia after a transplant. The method detects and monitors the level of Gal-1. [11]

Awards and honors

Related Research Articles

<span class="mw-page-title-main">Inflammation</span> Physical effects resulting from activation of the immune system

Inflammation is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function.

<span class="mw-page-title-main">Autoimmunity</span> Immune response against an organisms own healthy cells

In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". Prominent examples include celiac disease, diabetes mellitus type 1, Henoch–Schönlein purpura, systemic lupus erythematosus, Sjögren syndrome, eosinophilic granulomatosis with polyangiitis, Hashimoto's thyroiditis, Graves' disease, idiopathic thrombocytopenic purpura, Addison's disease, rheumatoid arthritis, ankylosing spondylitis, polymyositis, dermatomyositis, and multiple sclerosis. Autoimmune diseases are very often treated with steroids.

<span class="mw-page-title-main">Tumor necrosis factor</span> Immune system messenger protein which induces inflammation

Tumor necrosis factor (TNF), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors on other cells. It is a member of the tumor necrosis factor superfamily, a family of transmembrane proteins that are cytokines, chemical messengers of the immune system. Excessive production of TNF plays a critical role in several inflammatory diseases, and TNF-blocking drugs are often employed to treat these diseases.

<span class="mw-page-title-main">Endothelium</span> Layer of cells that line the inner surface of blood vessels

The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel wall.

Stromal cells, or mesenchymal stromal cells, are differentiating cells found in abundance within bone marrow but can also be seen all around the body. Stromal cells can become connective tissue cells of any organ, for example in the uterine mucosa (endometrium), prostate, bone marrow, lymph node and the ovary. They are cells that support the function of the parenchymal cells of that organ. The most common stromal cells include fibroblasts and pericytes. The term stromal comes from Latin stromat-, "bed covering", and Ancient Greek στρῶμα, strôma, "bed".

<span class="mw-page-title-main">RAGE (receptor)</span> Protein-coding gene in the species Homo sapiens

RAGE, also called AGER, is a 35 kilodalton transmembrane receptor of the immunoglobulin super family which was first characterized in 1992 by Neeper et al. Its name comes from its ability to bind advanced glycation endproducts (AGE), which include chiefly glycoproteins, the glycans of which have been modified non-enzymatically through the Maillard reaction. In view of its inflammatory function in innate immunity and its ability to detect a class of ligands through a common structural motif, RAGE is often referred to as a pattern recognition receptor. RAGE also has at least one other agonistic ligand: high mobility group protein B1 (HMGB1). HMGB1 is an intracellular DNA-binding protein important in chromatin remodeling which can be released by necrotic cells passively, and by active secretion from macrophages, natural killer cells, and dendritic cells.

<span class="mw-page-title-main">Interleukin 33</span> IL-33 induces helper T cells, mast cells, eosinophils and basophils to produce type 2 cytokines.

Interleukin 33 (IL-33) is a protein that in humans is encoded by the IL33 gene.

<span class="mw-page-title-main">Interleukin 19</span> Protein-coding gene in the species Homo sapiens

Interleukin 19 (IL-19) is an immunosuppressive protein that belongs to the IL-10 cytokine subfamily.

<span class="mw-page-title-main">Galectin</span> Protein family binding to β-galactoside sugars

Galectins are a class of proteins that bind specifically to β-galactoside sugars, such as N-acetyllactosamine, which can be bound to proteins by either N-linked or O-linked glycosylation. They are also termed S-type lectins due to their dependency on disulphide bonds for stability and carbohydrate binding. There have been about 15 galectins discovered in mammals, encoded by the LGALS genes, which are numbered in a consecutive manner. Only galectin-1, -2, -3, -4, -7, -7B, -8, -9, -9B, 9C, -10, -12, -13, -14, and -16 have been identified in humans. Galectin-5 and -6 are found in rodents, whereas galectin-11 and -15 are uniquely found in sheep and goats. Members of the galectin family have also been discovered in other mammals, birds, amphibians, fish, nematodes, sponges, and some fungi. Unlike the majority of lectins they are not membrane bound, but soluble proteins with both intra- and extracellular functions. They have distinct but overlapping distributions but found primarily in the cytosol, nucleus, extracellular matrix or in circulation. Although many galectins must be secreted, they do not have a typical signal peptide required for classical secretion. The mechanism and reason for this non-classical secretion pathway is unknown.

<span class="mw-page-title-main">Galectin-1</span> Protein-coding gene in the species Homo sapiens

Galectin-1 is a protein that in humans is encoded by the LGALS1 gene.

Interleukin 35 (IL-35) is a recently discovered anti-inflammatory cytokine from the IL-12 family. Member of IL-12 family - IL-35 is produced by wide range of regulatory lymphocytes and plays a role in immune suppression. IL-35 can block the development of Th1 and Th17 cells by limiting early T cell proliferation.

Gamma delta T cells are T cells that have a γδ T-cell receptor (TCR) on their surface. Most T cells are αβ T cells with TCR composed of two glycoprotein chains called α (alpha) and β (beta) TCR chains. In contrast, γδ T cells have a TCR that is made up of one γ (gamma) chain and one δ (delta) chain. This group of T cells is usually less common than αβ T cells. Their highest abundance is in the gut mucosa, within a population of lymphocytes known as intraepithelial lymphocytes (IELs).

<span class="mw-page-title-main">Autoimmune disease</span> Disorders of adaptive immune system

An autoimmune disease is a condition that results from an anomalous response of the adaptive immune system, wherein it mistakenly targets and attacks healthy, functioning parts of the body as if they were foreign organisms. It is estimated that there are more than 80 recognized autoimmune diseases, with recent scientific evidence suggesting the existence of potentially more than 100 distinct conditions. Nearly any body part can be involved.

Adipose tissue macrophages (ATMs) comprise resident macrophages present in adipose tissue. Besides adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells that includes pre-adipocytes, fibroblasts, vascular endothelial cells, and a large variety of immune cells. The latter ones are composed of mast cells, eosinophils, B cells, T cells and macrophages. The number of macrophages within adipose tissue differs depending on the metabolic status. As discovered by Rudolph Leibel and Anthony Ferrante et al. in 2003 at Columbia University, the percentage of macrophages within adipose tissue ranges from 10% in lean mice and humans up to 50% in obese leptin deficient mice, and up to 40% in obese humans. ATMs comprise nearly 50% of all immune cells in normal conditions, suggesting an important role in supporting normal functioning of the adipose tissue. Increased number of adipose tissue macrophages may correlate with increased production of pro-inflammatory molecules and might therefore contribute to the pathophysiological consequences of obesity, although is becoming recognized that in healthy conditions tissue-resident macrophages actively support a variety of critical physiological functions in nearly all organs and tissues, including adipose tissue.

Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells, derived from common lymphoid progenitors (CLPs). In response to pathogenic tissue damage, ILCs contribute to immunity via the secretion of signalling molecules, and the regulation of both innate and adaptive immune cells. ILCs are primarily tissue resident cells, found in both lymphoid, and non- lymphoid tissues, and rarely in the blood. They are particularly abundant at mucosal surfaces, playing a key role in mucosal immunity and homeostasis. Characteristics allowing their differentiation from other immune cells include the regular lymphoid morphology, absence of rearranged antigen receptors found on T cells and B cells, and phenotypic markers usually present on myeloid or dendritic cells.

Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of immune cells from the myeloid lineage.

<span class="mw-page-title-main">ILC2</span>

ILC2 cells, or type 2 innate lymphoid cells are a type of innate lymphoid cell. Not to be confused with the ILC. They are derived from common lymphoid progenitor and belong to the lymphoid lineage. These cells lack antigen specific B or T cell receptor because of the lack of recombination activating gene. ILC2s produce type 2 cytokines and are involved in responses to helminths, allergens, some viruses, such as influenza virus and cancer.

<span class="mw-page-title-main">Endothelial cell anergy</span> Defense mechanism of tumors against immunity

Endothelial cell anergy is a condition during the process of angiogenesis, where endothelial cells, the cells that line the inside of blood vessels, can no longer respond to inflammatory cytokines. These cytokines are necessary to induce the expression of cell adhesion molecules to allow leukocyte infiltration from the blood into the tissue at places of inflammation, such as a tumor. This condition, which protects the tumor from the immune system, is the result of exposure to angiogenic growth factors.

Roberto Paganelli is an Italian physician, clinical immunologist and academic. He is a Professor of Internal Medicine, UniCamillus International Medical University in Rome, Italy.

Apoptosis inhibitor of macrophage (AIM) is a protein produced by macrophages that regulates immune responses and inflammation. It plays a crucial role in key intracellular processes like lipid metabolism and apoptosis.

References

  1. ↑ Rabinovich, Gabriel A.; Gabrilovich, Dmitry; Sotomayor, Eduardo M. (April 2007). "Immunosuppressive Strategies that are Mediated by Tumor Cells". Annual Review of Immunology. 25 (1): 267–296. doi:10.1146/annurev.immunol.25.022106.141609. ISSN   0732-0582. PMC   2895922 . PMID   17134371.
  2. ↑ Yang, Ri-Yao; Rabinovich, Gabriel A.; Liu, Fu-Tong (June 2008). "Galectins: structure, function and therapeutic potential". Expert Reviews in Molecular Medicine. 10: e17. doi:10.1017/S1462399408000719. hdl: 11336/25865 . ISSN   1462-3994. PMID   18549522. S2CID   24193126.
  3. 1 2 3 4 "Mission | Rabinovich Lab". rabinovich-lab.com. Retrieved 2020-04-16.
  4. ↑ Rabinovich, Gabriel A.; Daly, Gordon; Dreja, Hanna; Tailor, Hitakshi; Riera, Clelia M.; Hirabayashi, Jun; Chernajovsky, Yuti (1999-08-02). "Recombinant Galectin-1 and Its Genetic Delivery Suppress Collagen-Induced Arthritis via T Cell Apoptosis". Journal of Experimental Medicine. 190 (3): 385–398. doi: 10.1084/jem.190.3.385 . ISSN   0022-1007. PMC   2195592 . PMID   10430627.
  5. ↑ Rabinovich, Gabriel A; Baum, Linda G; Tinari, Nicola; Paganelli, Roberto; Natoli, Clara; Liu, Fu-Tong; Iacobelli, Stefano (2002-06-01). "Galectins and their ligands: amplifiers, silencers or tuners of the inflammatory response?". Trends in Immunology. 23 (6): 313–320. doi:10.1016/S1471-4906(02)02232-9. hdl: 11336/30710 . ISSN   1471-4906. PMID   12072371.
  6. ↑ Rubinstein, Natalia; Alvarez, Mariano; Zwirner, Norberto W; Toscano, Marta A; Ilarregui, Juan M; Bravo, Alicia; Mordoh, José; Fainboim, Leonardo; Podhajcer, Osvaldo L; Rabinovich, Gabriel A (2004-03-01). "Targeted inhibition of galectin-1 gene expression in tumor cells results in heightened T cell-mediated rejection: A potential mechanism of tumor-immune privilege". Cancer Cell. 5 (3): 241–251. doi: 10.1016/S1535-6108(04)00024-8 . hdl: 11336/29418 . ISSN   1535-6108. PMID   15050916.
  7. ↑ Cumashi, Albana; Ushakova, Natalia A.; Preobrazhenskaya, Marina E.; D'Incecco, Armida; Piccoli, Antonio; Totani, Licia; Tinari, Nicola; Morozevich, Galina E.; Berman, Albert E.; Bilan, Maria I.; Usov, Anatolii I. (2007-05-01). "A comparative study of the anti-inflammatory, anticoagulant, antiangiogenic, and antiadhesive activities of nine different fucoidans from brown seaweeds". Glycobiology. 17 (5): 541–552. doi: 10.1093/glycob/cwm014 . hdl: 11336/29419 . ISSN   0959-6658. PMID   17296677.
  8. ↑ van Kooyk, Yvette; Rabinovich, Gabriel A. (June 2008). "Protein-glycan interactions in the control of innate and adaptive immune responses". Nature Immunology. 9 (6): 593–601. doi: 10.1038/ni.f.203 . hdl: 11336/25867 . ISSN   1529-2916. PMID   18490910.
  9. ↑ Toscano, Marta A.; Martínez Allo, Verónica C.; Cutine, Anabela M.; Rabinovich, Gabriel A.; Mariño, Karina V. (2018-04-01). "Untangling Galectin-Driven Regulatory Circuits in Autoimmune Inflammation". Trends in Molecular Medicine. 24 (4): 348–363. doi:10.1016/j.molmed.2018.02.008. hdl: 11336/89500 . ISSN   1471-4914. PMID   29555188.
  10. ↑ Maller, Sebastián M.; Cagnoni, Alejandro J.; Bannoud, Nadia; Sigaut, Lorena; Sáez, Juan M. Pérez; Pietrasanta, Lía I.; Yang, Ri-Yao; Liu, Fu-Tong; Croci, Diego O.; Lella, Santiago Di; Sundblad, Victoria (2020). "An adipose tissue galectin controls endothelial cell function via preferential recognition of 3-fucosylated glycans". The FASEB Journal. 34 (1): 735–753. doi: 10.1096/fj.201901817R . ISSN   1530-6860. PMID   31914594.
  11. ↑ USapplication 2020093920,Shipp, Margaret A.; Ouyang, Jing& Takeyama, Kunihikoet al.,"Compositions, kits, and methods for the diagnosis, prognosis, monitoring, treatment and modulation of post-transplant lymphoproliferative disorders and hypoxia associated angiogenesis disorders using galectin-1",published 2020-03-26, assigned to Dana-Farber Cancer Institute Inc., Brigham and Women's Hospital Inc., Consejo Nacional de Investigaciones Científicas y Técnicas & Fundación Sales.
  12. ↑ "Gabriel Rabinovich | Fundación Konex". www.fundacionkonex.org (in Spanish). Retrieved 2023-10-03.
  13. ↑ "Sandra Díaz y Gabriel Rabinovich fueron distinguidos con el Premio Konex de Brillante por su rol destacado en Ciencia y Tecnología". infobae (in European Spanish). 2023-09-29. Retrieved 2023-10-03.
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