George D. Yancopoulos (born 1959) is a Greek-American biomedical scientist who is the co-founder, president and chief scientific officer of Regeneron Pharmaceuticals.[1]
Yancopoulos is a member of the National Academy of Sciences, and the holder of more than 100 patents.[2] He is a principal inventor and developer of Regeneron's ten FDA-approved or -authorized treatments, as well as of Regeneron's foundational technologies for target and drug development, such as its proprietary TRAP technology, and the VelociGene and VelocImmune antibody technologies.[3][4]
Early life and education
Yancopoulos is the son of Greek immigrants, and spent his early childhood in Woodside, New York. As a student at the Bronx High School of Science, Yancopoulos was a top winner of the 1976 Westinghouse Science Talent Search. Intel and then Regeneron later assumed the title sponsorship for the Science Talent Search.[5]
He was elected to both the National Academy of Sciences[6] and the American Association for the Advancement of Science in 2004. According to a study by the Institute for Scientific Information, he was the eleventh most highly cited scientist in the world during the 1990s, and the only scientist from the biotechnology industry on the list.[7]
Yancopoulos was a graduate student in Fred Alt's laboratory at Columbia University in the 1980s. Much of Yancopoulos and Alt's work in immunology, including common recombination, accessibility control of recombination and scanning or tracking of recombinant action, has been recently validated.[8]
Yancopoulos joined Regeneron in its earliest days. Once there, he cloned novel families of growth factors, neurotrophic factors, ephrins/Ephs and angiopoietins, and elucidated the basis of how many receptors work.[9] His work has included study of how nerves regenerate[6] and how muscles connect to nerves.[10]
For example, the very first paper from his work at Regeneron documented the cloning of NT3 (Neurotrophic factor 3), a neurotrophic factor in the Nerve growth factor family.[11] His group also cloned receptors for neurotrophic factors, such as TrkB, the receptor for BDNF, and showed that they were sufficient to mediate signaling without the requirement of the Low affinity Nerve Growth Factor receptor (LNGFR).[12]
Yancopoulos and his colleagues discovered a receptor tyrosine kinase which they named "MuSK" (Muscle Specific Kinase, or MuSK protein). They went on to show that MuSK is required for the formation of the neuromuscular junction, the key structure which allows motor neurons to induce skeletal muscle to contract.[13] They next demonstrated that the ligand for MuSK is agrin, a protein secreted by the motor neuron to induce formation of the neuromuscular junction.[14]
What was also noteworthy from this period was the cloning of the receptor for the ciliary neurotrophic factor CNTF.[15] The understanding of this receptor induced Yancopoulos and his colleagues to use the receptor in a novel fashion, by making a secreted form so as to "trap" or inhibit the ligand's action. This documented the invention of the "receptor trap",[16] a concept which was used importantly in making a trap to inhibit the action of VEGF (Vascular endothelial growth factor).[17] The "VEGF Trap" was then used to design a medicine to treat Acute Macular Degeneration (AMD), a disease which causes blindness.
Yancopoulos was the first to propose making mouse models with genetically human immune systems ("Human mice").[18] This research led to Yancopoulos at Regeneron developing "the most valuable mouse ever made," bred to have immune systems that respond just as a human's would, so that it can be used for testing how the human body might react to various pharmaceuticals and other substances.[6]
Several important human antibodies, which were then tested for their use as medicines, have come from these mice. For example, a "cocktail," or mixture of three distinct antibodies to the Ebola virus resulted in treatment for Ebola.[19] More recently, Yancopolous and his colleagues developed a cocktail of antibodies, using the mouse with a human immune system, to block the SARS-CoV-2 virus in order to treat COVID-19.[20]
Career
Yancopoulos left academia in 1989 to become the founding scientist and chief scientific officer of Regeneron Pharmaceuticals with founder and chief executive officer Leonard Schleifer, M.D., Ph.D. In 2016, Yancopoulos was also named president of the company.[21]
Yancopoulos plays an active role in Regeneron's STEM (Science, Technology, Engineering and Math) Education commitments, including the Regeneron Science Talent Search, America's oldest high school science and math competition.[22]
In 2014, Yancopoulos led the launch of the Regeneron Genetics Center, a major initiative in human genetic research that has sequenced exomes from over 1,000,000 people as of February2020[update].[23][24]
Forbes magazine states Yancopoulos' financial stake in Regeneron has made him a billionaire. He is the first research and development chief in the pharmaceutical industry to become a billionaire.[25]
Awards
Yancopoulos won a NY/NJ CEO Lifetime Achievement Award in 2012.[26]
Yancopoulos has been awarded Columbia University's Stevens Triennial Prize for Research and its University Medal of Excellence for Distinguished Achievement.[27]
The George D. Yancopoulos Young Scientist Award is given at the Westchester Science & Engineering Fair.[29]
He was inducted into the Bronx Science Hall of Fame in 2017 and was recognized by the Yale School of Management, CEO Institute as a Legends in Leadership Award in 2017.[30][31]
In 2019, he received the Alexander Hamilton Award,[32] Columbia's highest honor for contributions to science and medicine, and was recognized by Forbes as one of America's 100 Most Innovative Leaders.[33]
Yancopoulos was recognized by Fortune in 2020 as one of the World's 25 Greatest Leaders: Heroes of the Pandemic.[34]
In 2021, Yancopoulos won the Roy Vagelos Humanitarian Award for REGEN-COV, Prix Galien Foundation[35] and the New York Intellectual Property Law Association's Inventors of the Year for REGEN-COV.[36]
Boards
Yancopoulos serves on a number of Boards, including on Regeneron's Board of Directors. He currently serves on the Columbia University Medical Center Board of Visitors, as Vice Chair starting in 2012;[37] the Board of Trustees for Cold Spring Harbor Laboratory, since 2015;[38] the Scientific Advisory Council, Alliance on Cancer Gene Therapy, since 2007;[39] the Scleroderma Research Foundation, Scientific Advisory Board, starting in 2004;[40] and the Pershing Square Cancer Research Alliance, Advisory Board, since 2018.[41]
Controversies
In 2020, Donald Trump and others in his administration were treated with REGEN-COV, Regeneron's experimental COVID-19 therapeutic, raising concerns that Regeneron had provided them with privileged access to the drug.[42][43] At the time, the drug was undergoing clinical trials in humans and not yet under an FDA emergency use authorization (EUA). However, as is typical for experimental drugs, the FDA "expanded access" regulation, technically known as 21 CFR 312.310, allowed Trump's physicians to request "compassionate use" of REGN-COV.[44] Compassionate use is granted by the FDA (not the drug developer) to individual patients when it is determined that "the probable risk to the person from the investigational drug is not greater than the probable risk from the disease or condition."[45] REGN-COV was developed using the same patented VelocImmune technology which produced the world's first cure to the Ebola virus.[46] The successful track record of VelocImmune technology at producing safe and effective monoclonal antibody treatments against viruses presumably contributed to the FDA's decision to grant compassionate use to Donald Trump.
Yancopoulos received unusual and preferential treatment from New York state related to his personal COVID-19 testing.[47]
Yancopoulos GD, Blackwell TK, Suh H, Hood L, Alt FW (January 1986). "Introduced T cell receptor variable region gene segments recombine in pre-B cells: evidence that B and T cells use a common recombinase". Cell. 44 (2): 251–9. doi:10.1016/0092-8674(86)90759-2. PMID3484682. S2CID35030279.
Boulton TG, Nye SH, Robbins DJ, etal. (May 1991). "ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF". Cell. 65 (4): 663–75. doi:10.1016/0092-8674(91)90098-J. PMID2032290. S2CID35051321.
Glass DJ, Nye SH, Hantzopoulos P, etal. (July 1991). "TrkB mediates BDNF/NT-3-dependent survival and proliferation in fibroblasts lacking the low affinity NGF receptor". Cell. 66 (2): 405–13. doi:10.1016/0092-8674(91)90629-D. PMID1649703. S2CID43626580.
Ip NY, Stitt TN, Tapley P, etal. (February 1993). "Similarities and differences in the way neurotrophins interact with the Trk receptors in neuronal and nonneuronal cells". Neuron. 10 (2): 137–49. doi:10.1016/0896-6273(93)90306-C. PMID7679912. S2CID46072027.
Davis S, Gale NW, Aldrich TH, etal. (November 1994). "Ligands for EPH-related receptor tyrosine kinases that require membrane attachment or clustering for activity". Science. 266 (5186): 816–9. Bibcode:1994Sci...266..816D. doi:10.1126/science.7973638. PMID7973638.
Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein that, in humans, is encoded by the BDNF gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the canonical nerve growth factor (NGF), a family which also includes NT-3 and NT-4/NT-5. Neurotrophic factors are found in the brain and the periphery. BDNF was first isolated from a pig brain in 1982 by Yves-Alain Barde and Hans Thoenen.
Neurotrophins are a family of proteins that induce the survival, development, and function of neurons.
Vascular endothelial growth factor, originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors, the platelet-derived growth factor family of cystine-knot growth factors. They are important signaling proteins involved in both vasculogenesis and angiogenesis.
Nerve growth factor (NGF) is a neurotrophic factor and neuropeptide primarily involved in the regulation of growth, maintenance, proliferation, and survival of certain target neurons. It is perhaps the prototypical growth factor, in that it was one of the first to be described. Since it was first isolated by Nobel laureates Rita Levi-Montalcini and Stanley Cohen in 1954, numerous biological processes involving NGF have been identified, two of them being the survival of pancreatic beta cells and the regulation of the immune system.
MuSK is a receptor tyrosine kinase required for the formation and maintenance of the neuromuscular junction. It is activated by a nerve-derived proteoglycan called agrin, which is similarly also required for neuromuscular junction formation.
Tropomyosin receptor kinase A (TrkA), also known as high affinity nerve growth factor receptor, neurotrophic tyrosine kinase receptor type 1, or TRK1-transforming tyrosine kinase protein is a protein that in humans is encoded by the NTRK1 gene.
Tropomyosin receptor kinase B (TrkB), also known as tyrosine receptor kinase B, or BDNF/NT-3 growth factors receptor or neurotrophic tyrosine kinase, receptor, type 2 is a protein that in humans is encoded by the NTRK2 gene. TrkB is a receptor for brain-derived neurotrophic factor (BDNF). The standard pronunciation for this protein is "track bee".
The p75 neurotrophin receptor (p75NTR) was first identified in 1973 as the low-affinity nerve growth factor receptor (LNGFR) before discovery that p75NTR bound other neurotrophins equally well as nerve growth factor. p75NTR is a neurotrophic factor receptor. Neurotrophic factor receptors bind Neurotrophins including Nerve growth factor, Neurotrophin-3, Brain-derived neurotrophic factor, and Neurotrophin-4. All neurotrophins bind to p75NTR. This also includes the immature pro-neurotrophin forms. Neurotrophic factor receptors, including p75NTR, are responsible for ensuring a proper density to target ratio of developing neurons, refining broader maps in development into precise connections. p75NTR is involved in pathways that promote neuronal survival and neuronal death.
Tropomyosin receptor kinase C (TrkC), also known as NT-3 growth factor receptor, neurotrophic tyrosine kinase receptor type 3, or TrkC tyrosine kinase is a protein that in humans is encoded by the NTRK3 gene.
Agrin is a large proteoglycan whose best-characterised role is in the development of the neuromuscular junction during embryogenesis. Agrin is named based on its involvement in the aggregation of acetylcholine receptors during synaptogenesis. In humans, this protein is encoded by the AGRN gene.
Neurotrophic factors (NTFs) are a family of biomolecules – nearly all of which are peptides or small proteins – that support the growth, survival, and differentiation of both developing and mature neurons. Most NTFs exert their trophic effects on neurons by signaling through tyrosine kinases, usually a receptor tyrosine kinase. In the mature nervous system, they promote neuronal survival, induce synaptic plasticity, and modulate the formation of long-term memories. Neurotrophic factors also promote the initial growth and development of neurons in the central nervous system and peripheral nervous system, and they are capable of regrowing damaged neurons in test tubes and animal models. Some neurotrophic factors are also released by the target tissue in order to guide the growth of developing axons. Most neurotrophic factors belong to one of three families: (1) neurotrophins, (2) glial cell-line derived neurotrophic factor family ligands (GFLs), and (3) neuropoietic cytokines. Each family has its own distinct cell signaling mechanisms, although the cellular responses elicited often do overlap.
Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins. Receptor tyrosine kinases have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Mutations in receptor tyrosine kinases lead to activation of a series of signalling cascades which have numerous effects on protein expression. The receptors are generally activated by dimerization and substrate presentation. Receptor tyrosine kinases are part of the larger family of protein tyrosine kinases, encompassing the receptor tyrosine kinase proteins which contain a transmembrane domain, as well as the non-receptor tyrosine kinases which do not possess transmembrane domains.
Dok-7 is a non-catalytic cytoplasmic adaptor protein that is expressed specifically in muscle and is essential for the formation of neuromuscular synapses. Further, Dok-7 contains pleckstrin homology (PH) and phosphotyrosine-binding (PTB) domains that are critical for Dok-7 function. Finally, mutations in Dok-7 are commonly found in patients with limb-girdle congenital myasthenia.
Neurotrophin-3 is a protein that in humans is encoded by the NTF3 gene.
Ciliary neurotrophic factor is a protein that in humans is encoded by the CNTF gene.
Neurotrophin-4 (NT-4), also known as neurotrophin-5 (NT-5), is a protein that in humans is encoded by the NTF4 gene. It is a neurotrophic factor that signals predominantly through the TrkB receptor tyrosine kinase. NT-4 was first discovered and isolated from xenopus and viper in the year 1991 by Finn Hallbook et.al
Angiopoietin 1 is a type of angiopoietin and is encoded by the gene ANGPT1.
Angiopoietin-1 receptor also known as CD202B is a protein that in humans is encoded by the TEK gene. Also known as TIE2, it is an angiopoietin receptor.
Trk receptors are a family of tyrosine kinases that regulates synaptic strength and plasticity in the mammalian nervous system. Trk receptors affect neuronal survival and differentiation through several signaling cascades. However, the activation of these receptors also has significant effects on functional properties of neurons.
Neurotrophic factor receptors or neurotrophin receptors are a group of growth factor receptors which specifically bind to neurotrophins.
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