Frances Brodsky

Last updated
Professor

Frances Brodsky

DPhil FMedSci
NationalityAmerican
Alma mater Harvard University
University of Oxford
Known forStudies of clathrin and vesicle trafficking
Scientific career
Institutions University College, London
University of California, San Francisco
Doctoral advisor Walter Bodmer
Jack Strominger

Frances Brodsky is an American cell biologist. She is known for her work on clathrin and its role in the function of the immune system. [1] She is a professor of cell biology and the director of the Division of Biosciences (part of the Faculty of Life Sciences) at University College London. She is the author of three scientific mystery novels under the pseudonym B.B. Jordan. She was the founding editor of the journal Traffic. [2]

Contents

Education

Brodsky earned her B.Sc. in biochemistry from Harvard University in 1976. She received a Marshall Scholarship to study in the UK and performed research in the laboratory of Walter Bodmer at Oxford University, obtaining a D. Phil. (Oxford's term for a Ph.D.) in 1979.

Career

After postdoctoral work at Harvard University and Stanford University, Brodsky joined Becton Dickinson as a program manager in cell biology in 1982. In 1987, she returned to academia as an assistant professor in the Department of Pharmacy and Pharmaceutical Chemistry at the University of California, San Francisco.

Brodsky's work straddles the interface of immunology and cell biology. She developed some of the first monoclonal antibodies to the major histocompatibility complex, a protein that is central to the immune system. [3] [4] She became interested in clathrin, a protein that is key to both inward and outward membrane trafficking in cells, shortly after its isolation by Barbara Pearse. She used monoclonal antibodies to map the structure of clathrin [5] [6] and to probe its assembly into its characteristic polyhedral structures. [7] [8] Clathrin-mediated endocytosis is involved in the uptake of antigens from outside the cell that are eventually presented on the surface of the cell by the major histocompatibility complex class II (MHC class II). Brodsky discovered that the pathway of MHC class II export meets the antigen import pathway in a specialized endocytic compartment where antigens can be processed into peptides and loaded onto the MHC class II molecule for presentation. [9] She also identified the site at which peptides are loaded onto MHC class I proteins. [10]

Brodsky has been a leader in analyzing the regulation of clathrin assembly [11] [12] [13] and the adaptor proteins that help capture specific cargoes in clathrin-coated vesicles. [14] [15] She has identified roles for clathrin isoforms in diseases such as diabetes [16] and myopathies, [17] and in controlling immunoglobulin class switching. [18]

In 2000, she founded Traffic: The International Journal of Intracellular Transport with Mark Marsh, Sandra Schmid, and Thomas Kreis, with the goal of creating “a central journal to gather together publications that are of most interest to those working on intracellular trafficking”. [2] In 2007, she stepped aside from the role of co-Editor to become Reviews Editor of Traffic. [19]

In 2015, after 28 years at UCSF, Brodsky moved back to the UK to lead the Division of Biosciences at University College London. [20]

In 2019, she was elected to the council of the Academy of Medical Sciences [21]

Awards

Mystery novels

Brodsky is the author of three mystery novels starring virologist Dr. Celeste Braun, all published by Berkley Prime Crime, under the pseudonym B.B. Jordan. In Principal Investigation (1997), [24] Braun foils a criminal who is threatening to cause an outbreak of a deadly virus; in Secondary Immunization (1999) [25] she uncovers a conspiracy that uses the immune systems of patients to carry information for a drug cartel; and in Triplet Code (2001) [26] she solves the mystery of the deaths of three colleagues.

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.

Histocompatibility, or tissue compatibility, is the property of having the same, or sufficiently similar, alleles of a set of genes called human leukocyte antigens (HLA), or major histocompatibility complex (MHC). Each individual expresses many unique HLA proteins on the surface of their cells, which signal to the immune system whether a cell is part of the self or an invading organism. T cells recognize foreign HLA molecules and trigger an immune response to destroy the foreign cells. Histocompatibility testing is most relevant for topics related to whole organ, tissue, or stem cell transplants, where the similarity or difference between the donor's HLA alleles and the recipient's triggers the immune system to reject the transplant. The wide variety of potential HLA alleles lead to unique combinations in individuals and make matching difficult.

<span class="mw-page-title-main">B cell</span> Type of white blood cell

B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or inserted into the plasma membrane where they serve as a part of B-cell receptors. When a naïve or memory B cell is activated by an antigen, it proliferates and differentiates into an antibody-secreting effector cell, known as a plasmablast or plasma cell. Additionally, B cells present antigens and secrete cytokines. In mammals, B cells mature in the bone marrow, which is at the core of most bones. In birds, B cells mature in the bursa of Fabricius, a lymphoid organ where they were first discovered by Chang and Glick, which is why the 'B' stands for bursa and not bone marrow as commonly believed.

<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">Human leukocyte antigen</span> Genes on human chromosome 6

The human leukocyte antigen (HLA) system or complex is a complex of genes on chromosome 6 in humans which encode cell-surface proteins responsible for regulation of the immune system. The HLA system is also known as the human version of the major histocompatibility complex (MHC) found in many animals.

An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that binds to the epitope is called a paratope. Although epitopes are usually non-self proteins, sequences derived from the host that can be recognized are also epitopes.

<span class="mw-page-title-main">Transplant rejection</span> Rejection of transplanted tissue by the recipients immune system

Transplant rejection occurs when transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the molecular similitude between donor and recipient and by use of immunosuppressant drugs after transplant.

<span class="mw-page-title-main">Plasma cell</span> White blood cell that secretes large volumes of antibodies

Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B lymphocytes and secrete large quantities of proteins called antibodies in response to being presented specific substances called antigens. These antibodies are transported from the plasma cells by the blood plasma and the lymphatic system to the site of the target antigen, where they initiate its neutralization or destruction. B cells differentiate into plasma cells that produce antibody molecules closely modeled after the receptors of the precursor B cell.

<span class="mw-page-title-main">CD40 (protein)</span> Mammalian protein found in Homo sapiens

Cluster of differentiation 40, CD40 is a type I transmembrane protein found on antigen-presenting cells and is required for their activation. The binding of CD154 (CD40L) on TH cells to CD40 activates antigen presenting cells and induces a variety of downstream effects.

Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted:

<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">Antonio Lanzavecchia</span> Italian and Swiss immunologist

Antonio Lanzavecchia is an Italian and Swiss immunologist. As a fellow of Collegio Borromeo he obtained a degree with honors in Medicine in 1976 from the University of Pavia where he specialized in Pediatrics and Infectious Diseases. He is Head Human Immunology Program, Istituto Nazionale di Genetica Molecolare-INGM, Milan and SVP Senior research Fellow, Humabs/Vir Biotechnology, Bellinzona and San Francisco (USA). Since 2017, he is also Professor at the Faculty of Biomedical Sciences of the Università della Svizzera italiana (USI).

<span class="mw-page-title-main">CD74</span> Mammalian protein found in Homo sapiens

HLA class II histocompatibility antigen gamma chain also known as HLA-DR antigens-associated invariant chain or CD74, is a protein that in humans is encoded by the CD74 gene. The invariant chain is a polypeptide which plays a critical role in antigen presentation. It is involved in the formation and transport of MHC class II peptide complexes for the generation of CD4+ T cell responses. The cell surface form of the invariant chain is known as CD74. CD74 is a cell surface receptor for the cytokine macrophage migration inhibitory factor (MIF).

<span class="mw-page-title-main">AP2M1</span> Protein-coding gene in the species Homo sapiens

AP-2 complex subunit mu is a protein that in humans is encoded by the AP2M1 gene.

<span class="mw-page-title-main">MHC class I polypeptide–related sequence A</span>

MHC class I polypeptide–related sequence A (MICA) is a highly polymorphic cell surface glycoprotein encoded by the MICA gene located within MHC locus. MICA is related to MHC class I and it has similar domain structure, however, it is not associated with β2-microglobulin nor binds peptides as conventional MHC class I molecules do. MICA rather functions as a stress-induced ligand (as a danger signal) for integral membrane protein receptor NKG2D ("natural-killer group 2, member D"). MICA is broadly recognized by NK cells, γδ T cells, and CD8+ αβ T cells which carry NKG2D receptor on their cell surface and which are activated via this interaction.

The immune network theory is a theory of how the adaptive immune system works, that has been developed since 1974 mainly by Niels Jerne and Geoffrey W. Hoffmann. The theory states that the immune system is an interacting network of lymphocytes and molecules that have variable (V) regions. These V regions bind not only to things that are foreign to the vertebrate, but also to other V regions within the system. The immune system is therefore seen as a network, with the components connected to each other by V-V interactions.

Complement-dependent cytotoxicity (CDC) is an effector function of IgG and IgM antibodies. When they are bound to surface antigen on target cell, the classical complement pathway is triggered by bonding protein C1q to these antibodies, resulting in formation of a membrane attack complex (MAC) and target cell lysis.

<span class="mw-page-title-main">Alessandro Sette</span> Italian immunologist (born 1960)

Alessandro Sette is an Italian immunologist. He was born on August 11, 1960, in Rome, Italy, to Pietro Sette, a prominent Italian businessman and politician, and Renata Sette. Sette is a professor at La Jolla Institute for Immunology (LJI). He is an adjunct professor at the University of California, San Diego. Sette studies the specific epitopes that the immune system recognizes in cancer, autoimmunity, allergy, and infectious diseases.

<span class="mw-page-title-main">Joan Lunney</span> Animal researcher

Joan Katherine Lunney is an American government scientific researcher at the United States Department of Agriculture's Agricultural Research Service. She is known for her work on swine immunology and genetics. She is an elected member of the American Association for the Advancement of Science.

Passive antibody therapy, also called serum therapy, is a subtype of passive immunotherapy that administers antibodies to target and kill pathogens or cancer cells. It is designed to draw support from foreign antibodies that are donated from a person, extracted from animals, or made in the laboratory to elicit an immune response instead of relying on the innate immune system to fight disease. It has a long history from the 18th century for treating infectious diseases and is now a common cancer treatment. The mechanism of actions include: antagonistic and agonistic reaction, complement-dependent cytotoxicity (CDC), and antibody-dependent cellular cytotoxicity (ADCC).

References

  1. ↑ Sedwick, Caitlin (2013-09-16). "Frances Brodsky: So you think you know all about clathrin?". The Journal of Cell Biology. 202 (6): 830–831. doi:10.1083/jcb.2026pi. ISSN   0021-9525. PMC   3776341 . PMID   24043697.
  2. 1 2 Jahn, Reinhard (2000). "Green and red lights at the cell". Nature. 407 (6802): 299. doi: 10.1038/35030250 . ISSN   0028-0836. S2CID   5245312.
  3. ↑ Parham, P.; Sehgal, P. K.; Brodsky, F. M. (1979-06-14). "Anti-HLA-A,B,C monoclonal antibodies with no alloantigenic specificity in humans define polymorphisms in other primate species". Nature. 279 (5714): 639–641. Bibcode:1979Natur.279..639P. doi:10.1038/279639a0. ISSN   0028-0836. PMID   88017. S2CID   4255372.
  4. ↑ Brodsky, F. M.; Bodmer, W. F.; Parham, P. (1979). "Characterization of a monoclonal anti-beta 2-microglobulin antibody and its use in the genetic and biochemical analysis of major histocompatibility antigens". European Journal of Immunology. 9 (7): 536–545. doi:10.1002/eji.1830090709. ISSN   0014-2980. PMID   91522. S2CID   45088807.
  5. ↑ Brodsky, F. M. (1985). "Clathrin structure characterized with monoclonal antibodies. I. Analysis of multiple antigenic sites". The Journal of Cell Biology. 101 (6): 2047–2054. doi:10.1083/jcb.101.6.2047. ISSN   0021-9525. PMC   2114023 . PMID   2415533.
  6. ↑ Brodsky, F. M. (1985). "Clathrin structure characterized with monoclonal antibodies. II. Identification of in vivo forms of clathrin". The Journal of Cell Biology. 101 (6): 2055–2062. doi:10.1083/jcb.101.6.2055. ISSN   0021-9525. PMC   2114020 . PMID   4066749.
  7. ↑ Blank, G. S.; Brodsky, F. M. (1986). "Site-specific disruption of clathrin assembly produces novel structures". The EMBO Journal. 5 (9): 2087–2095. doi:10.1002/j.1460-2075.1986.tb04470.x. ISSN   0261-4189. PMC   1167086 . PMID   3096714.
  8. ↑ Brodsky, F. M.; Galloway, C. J.; Blank, G. S.; Jackson, A. P.; Seow, H. F.; Drickamer, K.; Parham, P. (1987). "Localization of clathrin light-chain sequences mediating heavy-chain binding and coated vesicle diversity". Nature. 326 (6109): 203–205. Bibcode:1987Natur.326..203B. doi:10.1038/326203a0. ISSN   0028-0836. PMID   2434865. S2CID   4363913.
  9. ↑ Guagliardi, L. E.; Koppelman, B.; Blum, J. S.; Marks, M. S.; Cresswell, P.; Brodsky, F. M. (1990-01-11). "Co-localization of molecules involved in antigen processing and presentation in an early endocytic compartment". Nature. 343 (6254): 133–139. Bibcode:1990Natur.343..133G. doi:10.1038/343133a0. ISSN   0028-0836. PMID   2404209. S2CID   4240003.
  10. ↑ Bresnahan, P. A.; Barber, L. D.; Brodsky, F. M. (1997-04-01). "Localization of class I histocompatibility molecule assembly by subfractionation of the early secretory pathway". Human Immunology. 53 (2): 129–139. doi:10.1016/S0198-8859(97)00001-3. ISSN   0198-8859. PMID   9129970.
  11. ↑ Liu, S. H.; Wong, M. L.; Craik, C. S.; Brodsky, F. M. (1995-10-20). "Regulation of clathrin assembly and trimerization defined using recombinant triskelion hubs". Cell. 83 (2): 257–267. doi: 10.1016/0092-8674(95)90167-1 . ISSN   0092-8674. PMID   7585943.
  12. ↑ Stoddart, Angela; Dykstra, Michelle L.; Brown, Bruce K.; Song, Wenxia; Pierce, Susan K.; Brodsky, Frances M. (2002). "Lipid rafts unite signaling cascades with clathrin to regulate BCR internalization". Immunity. 17 (4): 451–462. doi: 10.1016/S1074-7613(02)00416-8 . ISSN   1074-7613. PMID   12387739.
  13. ↑ Wakeham, Diane E.; Chen, Chih-Ying; Greene, Barrie; Hwang, Peter K.; Brodsky, Frances M. (2003-10-01). "Clathrin self-assembly involves coordinated weak interactions favorable for cellular regulation". The EMBO Journal. 22 (19): 4980–4990. doi:10.1093/emboj/cdg511. ISSN   0261-4189. PMC   204494 . PMID   14517237.
  14. ↑ Greene, B.; Liu, S. H.; Wilde, A.; Brodsky, F. M. (2000). "Complete reconstitution of clathrin basket formation with recombinant protein fragments: adaptor control of clathrin self-assembly". Traffic. 1 (1): 69–75. doi: 10.1034/j.1600-0854.2000.010110.x . ISSN   1398-9219. PMID   11208061.
  15. ↑ Knuehl, Christine; Chen, Chih-Ying; Manalo, Venus; Hwang, Peter K.; Ota, Nobuyuki; Brodsky, Frances M. (2006). "Novel binding sites on clathrin and adaptors regulate distinct aspects of coat assembly". Traffic. 7 (12): 1688–1700. doi: 10.1111/j.1600-0854.2006.00499.x . ISSN   1398-9219. PMID   17052248.
  16. ↑ Vassilopoulos, Stéphane; Esk, Christopher; Hoshino, Sachiko; Funke, Birgit H.; Chen, Chih-Ying; Plocik, Alex M.; Wright, Woodring E.; Kucherlapati, Raju; Brodsky, Frances M. (2009-05-29). "A role for the CHC22 clathrin heavy-chain isoform in human glucose metabolism". Science. 324 (5931): 1192–1196. Bibcode:2009Sci...324.1192V. doi:10.1126/science.1171529. ISSN   1095-9203. PMC   2975026 . PMID   19478182.
  17. ↑ Hoshino, Sachiko; Sakamoto, Kazuho; Vassilopoulos, Stéphane; Camus, Stéphane M.; Griffin, Christine A.; Esk, Christopher; Torres, Jorge A.; Ohkoshi, Norio; Ishii, Akiko (2013). "The CHC22 clathrin-GLUT4 transport pathway contributes to skeletal muscle regeneration". PLOS ONE. 8 (10): e77787. Bibcode:2013PLoSO...877787H. doi: 10.1371/journal.pone.0077787 . ISSN   1932-6203. PMC   3813726 . PMID   24204966.
  18. ↑ Wu, Shuang; Majeed, Sophia R.; Evans, Timothy M.; Camus, Marine D.; Wong, Nicole M. L.; Schollmeier, Yvette; Park, Minjong; Muppidi, Jagan R.; Reboldi, Andrea (2016). "Clathrin light chains' role in selective endocytosis influences antibody isotype switching". Proceedings of the National Academy of Sciences of the United States of America. 113 (35): 9816–9821. doi: 10.1073/pnas.1611189113 . ISSN   1091-6490. PMC   5024586 . PMID   27540116.
  19. ↑ Brodsky, Frances M.; Marsh, Mark (2010). "Life History of the Journal TRAFFIC, Celebrating Ten Years of Publication". Traffic. 11 (1): 1–3. doi: 10.1111/j.1600-0854.2009.01004.x .
  20. ↑ "Department Says Farewell to Frances Brodsky | School of Pharmacy | UCSF". pharmacy.ucsf.edu. 13 November 2015. Retrieved 2019-03-17.
  21. ↑ "Academy of Medical Sciences Council Members 2019" . Retrieved 2019-07-27.
  22. ↑ "Frances Brodsky" . Retrieved 2019-03-17.
  23. ↑ "Women in Cell Biology Awards". ASCB. Retrieved 2019-03-17.
  24. ↑ Jordan, B. B. (1997). Principal investigation. New York: Berkley Prime Crime. ISBN   978-0425160909. OCLC   37832200.
  25. ↑ Jordan, B. B. (1999). Secondary immunization . New York: Berkley Prime Crime. ISBN   978-0425171189. OCLC   42654221.
  26. ↑ Jordan, B. B. (2001). Triplet code. New York: Berkley Prime Crime. ISBN   978-0425179208. OCLC   46718397.
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