Jacques Neefjes

Last updated
Jacques Neefjes
Sjaak Neefjes
Neefjes jacques wiki.jpg
Born8 December 1959 (1959-12-08) (age 63)
NationalityDutch
Education
Scientific career
Institutions Leiden University Medical Center

Jacques (Sjaak) Neefjes (born 8 December 1959) is a Dutch scientist who made breakthroughs in several research disciplines such as immunology, cell biology, chemistry, cancer biology, microbiology, and epidemiology. He is a professor at the Leiden University Medical Center. In 2020 he was one of four winners of the Spinoza Prize.

Contents

Biography

From 1979 to 1985, Jacques Neefjes studied Chemistry at the Vrije Universiteit Amsterdam. Then, he performed his Ph.D. studies at the Division of Cellular Biochemistry, in the Netherlands Cancer Institute (NKI) under the supervision of Prof. Dr. Ploegh in Amsterdam. During his thesis, he investigated the Cell Biological Aspect of MHC class I and II molecules. He obtained his Ph.D. degree on the 2nd of November 1990 with Cum Laude.

After his Ph.D., Jacques Neefjes did two post-doctoral visits. First, from 1991 to 1992, he visited the laboratory of Drs Benoit and Mathis at the Institut de Chimie Biologique, Strasbourg (France). Then, he obtained a 2-year fellowship from the European Molecular Biology Organization (EMBO) to visit the laboratory of Prof. Dr. Hämmerling at the German Cancer Research Center (DKFZ), in Heidelberg (Germany) from 1992 to 1993. In 1993, Jacques Neefjes became a staff member of the Division of Cellular Biochemistry at the NKI. In 1998, he became head of the division of Tumor Biology. From 1999 to 2016, he occupied the position of "Extraordinary professor" at the Leiden University. He was the Dean of the Graduate School Oncology Amsterdam (OOA) from 2000 to 2003.

Since 2016, he is head of the Cell and Chemical Biology department at the Leiden University Medical Center (the Netherlands).

Works

During his career, Jacques Neefjes has authored more than 280 scientific publications reaching more than 30,000 citations. [1] Neefjes’ discoveries on antigen presentation by the class I and II major histocompatibility complexes (MHC) constitute today's textbook knowledge. Through his exploration of the cell biology of the MHC, Jacques Neefjes became an expert on endocytosis and intracellular transport. In 2017, Neefjes and his team made fundamental discoveries regarding endosome positioning by the endoplasmic reticulum. [2] Neefjes further expanded his work on endosomes to phagosomes and intracellular bacteria. By combining chemistry, cell biology and biochemistry with genetic screens, Neefjes identified inhibitors to disturb bacterial survival strategies, representing one of the first antibiotics acting by targeting the host, rather than the pathogen. [3] In 2015, Neefjes has demonstrated that Salmonella infection promote cancer development. [4] Since 2019, Jacques Neefjes is co-financing the production of a promising cancer drug, Aclarubicin, which disappeared from the European market at the beginning of the 21st century. [5] [6] [7]

Distinction

Honours and awards

Honorary Lectures

Selected research articles

The Biosynthetic Pathway of MHC Class II but Not Class I Molecules Intersects the Endocytic Route.
Neefjes JJ, Stollorx V, Peters PJ, Geuze HJ, and Ploegh HL.
Cell. 1990. 61:171-183.

The major substrates for TAP in vivo are derived from newly synthesized proteins.
Reits EA, Vos JC, Grommé M, and Neefjes JJ.
Nature. 2000. 404:774–778.

Intracellular bacterial growth is controlled by a kinase network around PKB/AKT1.
Kuijl C, Savage ND, Marsman M, Tuin AW, Janssen L, Egan DA, Ketema M, Van Den Nieuwendijk R, Van Den Eeden SJ, Geluk A, Poot A, Van Der Marel G, Beijersbergen RL, Overkleeft H, Ottenhoff TH, and Neefjes JJ.
Nature. 2007. 450:725–730

An ER-Associated Pathway Defines Endosomal Architecture for Controlled Cargo Transport.
Jongsma ML, Berlin I, Wijdeven RH, Janssen L, Janssen GM, Garstka MA, Janssen H, Mensink M, van Veelen PA, Spaapen RM, and Neefjes JJ.
Cell. 2016. 166:152-166

Related Research Articles

<span class="mw-page-title-main">Antigen</span> Molecule triggering an immune response (antibody production) in the host

In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. The term antigen originally referred to a substance that is an antibody generator. Antigens can be proteins, peptides, polysaccharides, lipids, or nucleic acids.

<span class="mw-page-title-main">Signal transduction</span> Cascade of intracellular and molecular events for transmission/amplification of signals

Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellular response. Proteins responsible for detecting stimuli are generally termed receptors, although in some cases the term sensor is used. The changes elicited by ligand binding in a receptor give rise to a biochemical cascade, which is a chain of biochemical events known as a signaling pathway.

<span class="mw-page-title-main">Cytotoxic T cell</span> T cell that kills infected, damaged or cancerous cells

A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pathogens (such as viruses or bacteria), or cells that are damaged in other ways.

<span class="mw-page-title-main">T helper cell</span> Type of immune cell

The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considered essential in B cell antibody class switching, breaking cross-tolerance in dendritic cells, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages and neutrophils. CD4+ cells are mature Th cells that express the surface protein CD4. Genetic variation in regulatory elements expressed by CD4+ cells determines susceptibility to a broad class of autoimmune diseases.

<span class="mw-page-title-main">Major histocompatibility complex</span> Cell surface proteins, part of the acquired immune system

The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. These cell surface proteins are called MHC molecules.

<span class="mw-page-title-main">MHC class I</span> Protein of the immune system

MHC class I molecules are one of two primary classes of major histocompatibility complex (MHC) molecules and are found on the cell surface of all nucleated cells in the bodies of vertebrates. They also occur on platelets, but not on red blood cells. Their function is to display peptide fragments of proteins from within the cell to cytotoxic T cells; this will trigger an immediate response from the immune system against a particular non-self antigen displayed with the help of an MHC class I protein. Because MHC class I molecules present peptides derived from cytosolic proteins, the pathway of MHC class I presentation is often called cytosolic or endogenous pathway.

Cross-presentation is the ability of certain professional antigen-presenting cells (mostly dendritic cells) to take up, process and present extracellular antigens with MHC class I molecules to CD8 T cells (cytotoxic T cells). Cross-priming, the result of this process, describes the stimulation of naive cytotoxic CD8+ T cells into activated cytotoxic CD8+ T cells. This process is necessary for immunity against most tumors and against viruses that infect dendritic cells and sabotage their presentation of virus antigens. Cross presentation is also required for the induction of cytotoxic immunity by vaccination with protein antigens, for example, tumour vaccination.

<span class="mw-page-title-main">Antigen presentation</span> Vital immune process that is essential for T cell immune response triggering

Antigen presentation is a vital immune process that is essential for T cell immune response triggering. Because T cells recognize only fragmented antigens displayed on cell surfaces, antigen processing must occur before the antigen fragment, now bound to the major histocompatibility complex (MHC), is transported to the surface of the cell, a process known as presentation, where it can be recognized by a T-cell receptor. If there has been an infection with viruses or bacteria, the cell will present an endogenous or exogenous peptide fragment derived from the antigen by MHC molecules. There are two types of MHC molecules which differ in the behaviour of the antigens: MHC class I molecules (MHC-I) bind peptides from the cell cytosol, while peptides generated in the endocytic vesicles after internalisation are bound to MHC class II (MHC-II). Cellular membranes separate these two cellular environments - intracellular and extracellular. Each T cell can only recognize tens to hundreds of copies of a unique sequence of a single peptide among thousands of other peptides presented on the same cell, because an MHC molecule in one cell can bind to quite a large range of peptides. Predicting which antigens will be presented to the immune system by a certain MHC/HLA type is difficult, but the technology involved is improving.

<span class="mw-page-title-main">MHC class II</span> Protein of the immune system

MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial cells, and B cells. These cells are important in initiating immune responses.

<span class="mw-page-title-main">Cancer immunology</span> Study of the role of the immune system in cancer

Cancer immunology is an interdisciplinary branch of biology that is concerned with understanding the role of the immune system in the progression and development of cancer; the most well known application is cancer immunotherapy, which utilises the immune system as a treatment for cancer. Cancer immunosurveillance and immunoediting are based on protection against development of tumors in animal systems and (ii) identification of targets for immune recognition of human cancer.

Human leukocyte histocompatibility complex DO (HLA-DO) is an intracellular, dimeric non-classical Major Histocompatibility Complex (MHC) class II protein composed of α- and β-subunits which interact with HLA-DM in order to fine tune immunodominant epitope selection. As a non-classical MHC class II molecule, HLA-DO is a non-polymorphic accessory protein that aids in antigenic peptide chaperoning and loading, as opposed to its classical counterparts, which are polymorphic and involved in antigen presentation. Though more remains to be elucidated about the function of HLA-DO, its unique distribution in the mammalian body—namely, the exclusive expression of HLA-DO in B cells, thymic medullary epithelial cells, and dendritic cells—indicate that it may be of physiological importance and has inspired further research. Although HLA-DM can be found without HLA-DO, HLA-DO is only found in complex with HLA-DM and exhibits instability in the absence of HLA-DM. The evolutionary conservation of both DM and DO, further denote its biological significance and potential to confer evolutionary benefits to its host.

Interleukin-28 receptor is a type II cytokine receptor found largely in epithelial cells. It binds type 3 interferons, interleukin-28 A, Interleukin-28B, interleukin 29 and interferon lambda 4. It consists of an α chain and shares a common β subunit with the interleukin-10 receptor. Binding to the interleukin-28 receptor, which is restricted to select cell types, is important for fighting infection. Binding of the type 3 interferons to the receptor results in activation of the JAK/STAT signaling pathway.

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

Aclarubicin (INN) or aclacinomycin A is an anthracycline drug that is used in the treatment of cancer. Soil bacteria Streptomyces galilaeus can produce aclarubicin. It can induce histone eviction from chromatin upon intercalation.

<span class="mw-page-title-main">NKG2D</span> Protein-coding gene in the species Homo sapiens

NKG2D is an activating receptor (transmembrane protein) belonging to the NKG2 family of C-type lectin-like receptors. NKG2D is encoded by KLRK1 (killer cell lectin like receptor K1) gene which is located in the NK-gene complex (NKC) situated on chromosome 6 in mice and chromosome 12 in humans. In mice, it is expressed by NK cells, NK1.1+ T cells, γδ T cells, activated CD8+ αβ T cells and activated macrophages. In humans, it is expressed by NK cells, γδ T cells and CD8+ αβ T cells. NKG2D recognizes induced-self proteins from MIC and RAET1/ULBP families which appear on the surface of stressed, malignant transformed, and infected cells.

Marcel R.M. van den Brink is a Dutch oncologist and researcher at Memorial Sloan Kettering Cancer Center known for his research in hematopoietic stem cell transplantation for cancer patients.

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

Motile sperm domain containing 1 is a protein that in humans is encoded by the MOSPD1 gene.

<span class="mw-page-title-main">Jean Pieters</span> Dutch biochemist

Jean Pieters is a Dutch biochemist and Professor at the Biozentrum of the University of Basel, Switzerland.

Peter J. Peters is a professor of nanobiology and a distinguished university professor at Maastricht University. Peters is best known for his work in electron microscopy (EM) and cellular immunology. He is the founder and director of the Institute of Nanoscopy.

Jannie G. Keyser-Borst is a Dutch cancer immunologist. She became Professor at Leiden University on 16 January 2019 At the Leiden University Medical Center she currently runs a research group investigating the regulation of the T cell response

Cornelis Joseph Maria Melief is a globally recognised immunology expert specialising in cancer immunology and immunotherapy, with special focus on therapeutic cancer vaccines. He is Emeritus Professor, former head of the Department of Immunohematology and Blood Transfusion at the Leiden University Medical Center, and Chief Scientific Officer at ISA Therapeutics in Netherlands. He is known for his work in the field of cancer immunology, devising new cancer therapies based on the activation of the patient’s own immune system.

References

  1. "Jacques Neefjes".
  2. Jongsma, Marlieke L.M.; Berlin, Ilana; Wijdeven, Ruud H.M.; Janssen, Lennert; Janssen, George M.C.; Garstka, Malgorzata A.; Janssen, Hans; Mensink, Mark; van Veelen, Peter A.; Spaapen, Robbert M.; Neefjes, Jacques (June 2016). "An ER-Associated Pathway Defines Endosomal Architecture for Controlled Cargo Transport". Cell. 166 (1): 152–166. doi:10.1016/j.cell.2016.05.078. PMC   4930482 . PMID   27368102.
  3. Kuijl, Coenraad; Savage, Nigel D. L.; Marsman, Marije; Tuin, Adriaan W.; Janssen, Lennert; Egan, David A.; Ketema, Mirjam; van den Nieuwendijk, Rian; van den Eeden, Susan J. F.; Geluk, Annemieke; Poot, Alex (November 2007). "Intracellular bacterial growth is controlled by a kinase network around PKB/AKT1". Nature. 450 (7170): 725–730. Bibcode:2007Natur.450..725K. doi:10.1038/nature06345. hdl: 1887/3209535 . ISSN   0028-0836. PMID   18046412. S2CID   23274247.
  4. Scanu, Tiziana; Spaapen, Robbert M.; Bakker, Jeroen M.; Pratap, Chandra Bhan; Wu, Lin-en; Hofland, Ingrid; Broeks, Annegien; Shukla, Vijay Kumar; Kumar, Mohan; Janssen, Hans; Song, Ji-Ying (2015-06-10). "Salmonella Manipulation of Host Signaling Pathways Provokes Cellular Transformation Associated with Gallbladder Carcinoma". Cell Host & Microbe. 17 (6): 763–774. doi: 10.1016/j.chom.2015.05.002 . ISSN   1931-3128. PMID   26028364.
  5. de Visser, Ellen; van der Zwaal, Manon; Jockel, Judith (March 2, 2019). "Hoe de erfenis van Els Borst mogelijk kankerpatiënten kan helpen". Volkskrant Kijk Verder (in Dutch). Retrieved 2019-10-02.
  6. "Nooit de makkelijkste weg - interview met Sjaak Neefjes, hoogleraar chemische immunologie aan de Universiteit Leiden en spreker op 2 oktober". Labtechnology (in Dutch). 2019-09-16. Retrieved 2019-10-02.
  7. Visser, Ellen de (2019-03-02). "Oud-minister Els Borst helpt postuum mee aan terugkeer kankermedicijn". de Volkskrant (in Dutch). Retrieved 2019-10-02.
  8. "Jacques Neefjes". Academia Europaea. Archived from the original on 28 March 2019.
  9. "Group 6: Cellular and Molecular biology". Norwegian Academy of Science and Letters. Retrieved 11 April 2020.
  10. "Jacques Neefjes". Royal Netherlands Academy of Arts and Sciences. Archived from the original on 24 September 2019.
  11. "Prof. Sjaak Neefjes". Netherlands Organisation for Scientific Research. Archived from the original on 6 November 2020.