Douglas R. Green

Last updated
Douglas R. Green
Doug Green.jpg
Born
Douglas R Green

February 1955 (age 66–67)
United States
NationalityAmerican
Known for Apoptosis research
Scientific career
FieldsCell Death, Cancer Biology, Immunology
Institutions St. Jude Children's Research Hospital
Thesis Contrasuppression: An Immunoregulatory T Cell Activity  (1981)
Doctoral advisor Richard K. Gershon
Website www.stjude.org/green

Douglas Green (born 1955), is an American biologist. He holds the Peter C. Doherty Endowed Chair of Immunology in St. Jude Children's Research Hospital. His research has focused on the process of active cell death and cell survival, extending from the role of cell death in cancer regulation and immune responses in the whole organism to the molecular events directing the death of the cell. Green was editor in chief of the journal Oncogene from 2009-2016, is a Deputy Editor of the journal "Science Advances" and the author of the book Cell Death, Means To An End.

Contents

Education

Green attended high school in Ashland, MA. He graduated magna cum laude from the Yale University with a Bachelor of Science in Biology and Distinction in Biology in 1977. After training at MIT during 1977 and 1978, he graduated in 1981 with a PhD from Yale University, where he studied immunology with Richard K. Gershon.

Green joined the faculty at the University of Alberta in Edmonton in 1985. [1] In 1990, Green moved to the La Jolla Institute for Allergy and Immunology, where he became Head of the Division of Cellular Immunology. [1] In 2005, he moved to St. Jude Children's Research Hospital to become the Peter C. Doherty Endowed Chair of the Department of Immunology. [1] [2]

Research

After many studies on immunological tolerance, Green's work on cell death began with his discovery of activation-induced apoptosis in T lymphocytes, [3] [4] the role of c-Myc in this process [5] and the finding that Bcl-2 cooperates with Myc in oncogenesis by blocking apoptosis. [6] More recently, he discovered the process of LC3-associated phagocytosis, which links the autophagy pathway to phagosome maturation. [7] Other areas of interest include regulated necrosis, [8] metabolic reprogramming in T lymphocytes, [9] and the function of the tumor suppressor, p53. [10] As of 2014 he had published many chapters and books and over 500 papers, making him one of the world's most cited molecular biologists. [11] He is listed in:

Recognition

Green has received many awards, among these the E.J. Boell Award (Biology) (Yale, 1977), the J.S. Nicholas Award (Zoology) (Yale, 1981), Alberta Heritage Scholar (AHFMR 1985-1990), the Outstanding Teacher Award (Alberta, 1990), Ashland Public School System Hall of Fame [12] (Ashland, MA 1998), MERIT Award, NIGMS (2002), the International Cell Death Society Prize [13] (2009), Einstein Professorship (China, 2011). He is an Honorary Fellow of Trinity College, Dublin (2010) [14] and Dottore Honoris Causa of Rome University Tor Vergata (2016). [15] Green was elected to the Royal Society of Canada in 2018, the United States National Academy of Sciences in 2020, [16] and the American Association for the Advancement of Science (AAAS) Fellow in 2021. [17]

Related Research Articles

Apoptosis Programmed cell death in multicellular organisms

Apoptosis is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, D.N.A. fragmentation, and mRNA decay. The average adult human loses between 50 and 70 billion cells each day due to apoptosis. For an average human child between eight and fourteen years old, approximately twenty to thirty billion cells die per day.

Cytotoxic T cell 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.

Natural killer cell Type of cytotoxic lymphocyte

Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of innate lymphoid cells (ILC) and represent 5–20% of all circulating lymphocytes in humans. The role of NK cells is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. NK cells provide rapid responses to virus-infected cell and other intracellular pathogens acting at around 3 days after infection, and respond to tumor formation. Typically, immune cells detect the major histocompatibility complex (MHC) presented on infected cell surfaces, triggering cytokine release, causing the death of the infected cell by lysis or apoptosis. NK cells are unique, however, as they have the ability to recognize and kill stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction. They were named "natural killers" because of the notion that they do not require activation to kill cells that are missing "self" markers of MHC class 1. This role is especially important because harmful cells that are missing MHC I markers cannot be detected and destroyed by other immune cells, such as T lymphocyte cells.

Fas ligand

Fas ligand is a type-II transmembrane protein that belongs to the tumor necrosis factor (TNF) family. Its binding with its receptor induces apoptosis. Fas ligand/receptor interactions play an important role in the regulation of the immune system and the progression of cancer.

Myc is a family of regulator genes and proto-oncogenes that code for transcription factors. The Myc family consists of three related human genes: c-myc (MYC), l-myc (MYCL), and n-myc (MYCN). c-myc was the first gene to be discovered in this family, due to homology with the viral gene v-myc.

Fas receptor

The Fas receptor, also known as Fas, FasR, apoptosis antigen 1, cluster of differentiation 95 (CD95) or tumor necrosis factor receptor superfamily member 6 (TNFRSF6), is a protein that in humans is encoded by the FAS gene. Fas was first identified using a monoclonal antibody generated by immunizing mice with the FS-7 cell line. Thus, the name Fas is derived from FS-7-associated surface antigen.

FADD

Fas-associated protein with death domain (FADD), also called MORT1, is encoded by the FADD gene on the 11q13.3 region of chromosome 11 in humans.

Chemokine ligand 1 (CCL1) is also known as small inducible cytokine A1 and I-309 in humans. CCL1 is a small glycoprotein that belongs to the CC chemokine family.

CD19 biomarker for B cell lineage

B-lymphocyte antigen CD19, also known as CD19 molecule, B-Lymphocyte Surface Antigen B4, T-Cell Surface Antigen Leu-12 and CVID3 is a transmembrane protein that in humans is encoded by the gene CD19. In humans, CD19 is expressed in all B lineage cells. Contrary to some early doubts, human plasma cells do express CD19, as confirmed by others. CD19 plays two major roles in human B cells: on the one hand, it acts as an adaptor protein to recruit cytoplasmic signaling proteins to the membrane; on the other, it works within the CD19/CD21 complex to decrease the threshold for B cell receptor signaling pathways. Due to its presence on all B cells, it is a biomarker for B lymphocyte development, lymphoma diagnosis and can be utilized as a target for leukemia immunotherapies.

B-cell activating factor

B-cell activating factor (BAFF) also known as tumor necrosis factor ligand superfamily member 13B is a protein that in humans is encoded by the TNFSF13B gene. BAFF is also known as B Lymphocyte Stimulator (BLyS) and TNF- and APOL-related leukocyte expressed ligand (TALL-1) and the Dendritic cell-derived TNF-like molecule.

Cancer immunology

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.

RIPK1

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions in a variety of cellular pathways related to both cell survival and death. In terms of cell death, RIPK1 plays a role in apoptosis and necroptosis. Some of the cell survival pathways RIPK1 participates in include NF-κB, Akt, and JNK.

LIGHT (protein) Secreted protein of the TNF superfamily

LIGHT, also known as tumor necrosis factor superfamily member 14 (TNFSF14), is a secreted protein of the TNF superfamily. It is recognized by herpesvirus entry mediator (HVEM), as well as decoy receptor 3.

Death receptor 3

Death receptor 3 (DR3), also known as tumor necrosis factor receptor superfamily member 25 (TNFRSF25), is a cell surface receptor of the tumor necrosis factor receptor superfamily which mediates apoptotic signalling and differentiation. Its only known TNFSF ligand is TNF-like protein 1A (TL1A).

LAG3

Lymphocyte-activation gene 3, also known as LAG-3, is a protein which in humans is encoded by the LAG3 gene. LAG3, which was discovered in 1990 and was designated CD223 after the Seventh Human Leucocyte Differentiation Antigen Workshop in 2000, is a cell surface molecule with diverse biologic effects on T cell function. It is an immune checkpoint receptor and as such is the target of various drug development programs by pharmaceutical companies seeking to develop new treatments for cancer and autoimmune disorders. In soluble form it is also being developed as a cancer drug in its own right.

Necroptosis Programmed form of necrosis, or inflammatory cell death

Necroptosis is a programmed form of necrosis, or inflammatory cell death. Conventionally, necrosis is associated with unprogrammed cell death resulting from cellular damage or infiltration by pathogens, in contrast to orderly, programmed cell death via apoptosis. The discovery of necroptosis showed that cells can execute necrosis in a programmed fashion and that apoptosis is not always the preferred form of cell death. Furthermore, the immunogenic nature of necroptosis favors its participation in certain circumstances, such as aiding in defence against pathogens by the immune system. Necroptosis is well defined as a viral defense mechanism, allowing the cell to undergo "cellular suicide" in a caspase-independent fashion in the presence of viral caspase inhibitors to restrict virus replication. In addition to being a response to disease, necroptosis has also been characterized as a component of inflammatory diseases such as Crohn's disease, pancreatitis, and myocardial infarction.

Immunogenic cell death is any type of cell death eliciting an immune response. Both accidental cell death and regulated cell death can result in immune response. Immunogenic cell death contrasts to forms of cell death that do not elicit any response or even mediate immune tolerance.

AICD is programmed cell death caused by the interaction of Fas receptors and Fas ligands. AICD is a negative regulator of activated T lymphocytes that results from repeated stimulation of their T-cell receptors (TCR) and helps to maintain peripheral immune tolerance. Alteration of the process may lead to autoimmune diseases.

Vishva Dixit

Vishva Mitra Dixit is a physician of Indian origin who is the current Vice President of Discovery Research at Genentech.

References

  1. 1 2 3 "Major Symposium Speaker: Douglas Green". International Congress of Immunology. Retrieved 11 July 2019.
  2. ↑ "Douglas R. Green, PhD". St Jude Children's Research Hospital. Retrieved 11 July 2019.
  3. ↑ Shi, Y. F.; Sahai, B. M.; Green, D. R. (1989). "Cyclosporin a inhibits activation-induced cell death in T-cell hybridomas and thymocytes". Nature. 339 (6226): 625–6. doi:10.1038/339625a0. PMID   2786609. S2CID   13603645.
  4. ↑ Shi, Y. F.; Szalay, M. G.; Paskar, L; Sahai, B. M.; Boyer, M; Singh, B; Green, D. R. (1990). "Activation-induced cell death in T cell hybridomas is due to apoptosis. Morphologic aspects and DNA fragmentation". Journal of Immunology. 144 (9): 3326–33. PMID   1691753.
  5. ↑ Shi, Y; Glynn, J. M.; Guilbert, L. J.; Cotter, T. G.; Bissonnette, R. P.; Green, D. R. (1992). "Role for c-myc in activation-induced apoptotic cell death in T cell hybridomas". Science. 257 (5067): 212–4. doi:10.1126/science.1378649. PMID   1378649.
  6. ↑ Bissonnette, R. P.; Echeverri, F; Mahboubi, A; Green, D. R. (1992). "Apoptotic cell death induced by c-myc is inhibited by bcl-2". Nature. 359 (6395): 552–4. doi:10.1038/359552a0. PMID   1406975. S2CID   4276740.
  7. ↑ Sanjuan, M. A.; Dillon, C. P.; Tait, S. W.; Moshiach, S; Dorsey, F; Connell, S; Komatsu, M; Tanaka, K; Cleveland, J. L.; Withoff, S; Green, D. R. (2007). "Toll-like receptor signalling in macrophages links the autophagy pathway to phagocytosis". Nature. 450 (7173): 1253–7. doi:10.1038/nature06421. PMID   18097414. S2CID   4406473.
  8. ↑ Dillon, C. P.; Weinlich, R; Rodriguez, D. A.; Cripps, J. G.; Quarato, G; Gurung, P; Verbist, K. C.; Brewer, T. L.; Llambi, F; Gong, Y. N.; Janke, L. J.; Kelliher, M. A.; Kanneganti, T. D.; Green, D. R. (2014). "RIPK1 blocks early postnatal lethality mediated by caspase-8 and RIPK3". Cell. 157 (5): 1189–202. doi:10.1016/j.cell.2014.04.018. PMC   4068710 . PMID   24813850.
  9. ↑ Wang, R; Dillon, C. P.; Shi, L. Z.; Milasta, S; Carter, R; Finkelstein, D; McCormick, L. L.; Fitzgerald, P; Chi, H; Munger, J; Green, D. R. (2011). "The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation". Immunity. 35 (6): 871–82. doi:10.1016/j.immuni.2011.09.021. PMC   3248798 . PMID   22195744.
  10. ↑ Chipuk, J. E.; Kuwana, T; Bouchier-Hayes, L; Droin, N. M.; Newmeyer, D. D.; Schuler, M; Green, D. R. (2004). "Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis". Science. 303 (5660): 1010–4. doi:10.1126/science.1092734. PMID   14963330. S2CID   9793389.
  11. ↑ "ISI - highlycited.com" . Retrieved 2015-02-06.
  12. ↑ Hall of Fame
  13. ↑ International Cell Death Society Prize Archived February 25, 2015, at the Wayback Machine
  14. ↑ Trinity College Fellows Scholars 2010
  15. ↑ Dottorato Honoris Causa in 'Biochimica e Biologia Molecolare' a Douglas R. Green
  16. ↑ News from the National Academy of Sciences
  17. ↑ 2021 AAAS Fellows
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