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Frances (Fran) Platt
FMedSci FRS MAE
Alma materImperial College London
University of Bath
Scientific career
FieldsPharmacology
Lysosomal storage diseases
InstitutionsWashington University School of Medicine
University of Oxford
Websiteplattlab.nsms.ox.ac.uk

Frances Mary Platt (née Judson) FMedSci FRS MAE is a biologist whose research has focused on biochemistry and pharmacology[1] Her research investigates rare genetic disorders known as lysosomal storage diseases, which are progressive conditions that typically lead to neurodegeneration. She is a Professor at the University of Oxford and currently Head of the Department of Pharmacology. She was elected Fellow of the Academy of Medical Sciences in 2011, and Fellow of the Royal Society in 2021.[2][3]

Early life and education

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Platt was born in Shipley, West Yorkshire. Since childhood she has had a strong interest in science and the natural world and took a degree in zoology at Imperial College London. Platt went to the University of Bath for a PhD studying insect endocrinology.

Research and career

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In 1986, Platt moved to the US as a postdoctoral researcher at Washington University School of Medicine, where she investigated cell surface molecules on B cells in germinal centres[4][5].In 1987 the head of the research team, Joseph Davie MD PhD moved to the pharmaceutical arm of Monsanto (GD Searle), where Platt learnt about industrial research and started working on antiviral drugs.

In 1989 she moved back to the UK as a Senior Research Fellow in the Glycobiology Institute, Department of Biochemistry in the University of Oxford. In 1996 Platt was the recipient of a five-year Lister Institute Senior Research Fellowship. In 2008 she became Professor of Biochemistry and Pharmacology in the Department of Pharmacology and Head of the department in 2020.[1]

Platt researches genetic disorders known as lysosomal storage diseases.[6] The lysosome is an organelle within cells that is involved with breaking down large molecules. When it goes wrong, molecules accumulate in the lysosome resulting in lysosomal storage diseases.

Her expertise relates to glycosphingolipids (GSL) and glycosphingolipid lysosomal storage diseases. Together with her colleagues Terry Butters and Raymond Dwek, Platt pioneered a novel approach to treat these genetic disorders that has led to the development of an approved drug (miglustat) for type 1 Gaucher disease and Niemann-Pick disease type C disease.[7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] She is an academic co-founder of the company IntraBio[26] and her translational work has continued as the companies lead drug Aqneursa[27] was FDA approved in September 2024 for the treatment of Niemann-Pick disease type C. Currently her research focuses on the pathophysiology and treatment of lysosomal storage diseases[28][29][30][31][32][33] and their links to Parkinson's disease.[34]

Awards and honours

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Selected publications

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  • First paper identifying the drug NB-DNJ (miglustat) as a glycosphingolipid biosynthesis inhibitor - F.M. Platt, G.R. Neises, R.A. Dwek, and T.D. Butters (1994) N-butyldeoxynojirimycin is a novel inhibitor of glycolipid biosynthesis J. Biol. Chem. 269, 8362–8365. https://pubmed.ncbi.nlm.nih.gov/8132559/
  • First study to show that miglustat crosses the blood-brain barrier and can reduce glycosphingolipid storage in the brain - Platt, F. M., Neises, G.R., Reinkensmeier,G., Townsend, M.J., Perry, V.H., Proia, R.L., Winchester, B., Dwek, R.A. and Butters, T.D. (1997) Prevention of lysosomal storage in Tay-Sachs mice treated with N-butyldeoxynojirimycin. Science, 276, 428–431. https://doi.org/10.1126/science.276.5311.428
  • Study reporting the pivotal clinical trial of miglustat in patients with type 1 Gaucher disease and demonstrated efficacy. This study led to approval of miglustat by the EMA and FDA in 2002/3 - T.M., Lachmann, R.H., Hollak, C.E.M., Aerts, J.M.F.G., van Weely, S., Hrebicek, M., Platt, F.M., Butters, T.D., Dwek, R.A., Moyses, C., Gow, I.R., Elstein, D. and Zimran, A. (2000) Novel oral treatment of Gaucher's disease with N-butyldeoxynojirmicin (OGT 918) to decrease substrate biosynthesis Lancet. 355, 1481–1485. https://doi.org/10.1016/s0140-6736(00)02161-9
  • A pivotal study showing that activation of the innate immune system is a common hallmark of lysosomal disorders of the brain and a new therapeutic target - Jeyakumar, M., Thomas, R., Eliott-Smith, E., van der Spoel, A., d’Azzo, A., Perry, V.H., Butters, T.D., Dwek, RA. and Platt, F.M. (2003) Central nervous system inflammation is a hallmark of pathogenesis in mouse models of GM1 and GM2 gangliosidosis. Brain, 126, 974–987. https://doi.org/10.1093/brain/awg089

References

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  1. ^ a b Frances Platt, Head of Department - https://www.pharm.ox.ac.uk/team/frances-platt
  2. ^ a b "Professor Fran Platt FMedSci FRS". Royal Society.
  3. ^ Frances M. Platt, PhD. The Michael J Fox Foundation for Parkinson’s Research https://www.michaeljfox.org/researcher/frances-m-platt-phd
  4. ^ Hawrylowicz, C. M.; Santoro, S. A.; Platt, F. M.; Unanue, E. R. (1989). "Hawrylowicz CM, Santoro SA, Platt FM, Unanue ER. Activated platelets express IL-1 activity. J Immunol. 1989 Dec 15;143(12):4015-8. PMID: 2592766". Journal of Immunology (Baltimore, Md. : 1950). 143 (12): 4015–4018. doi:10.4049/jimmunol.143.12.4015. PMID 2592766.
  5. ^ Platt, F. M.; Cebra-Thomas, J. A.; Baum, C. M.; Davie, J. M.; McKearn, J. P. (1992). "Platt FM, Cebra-Thomas JA, Baum CM, Davie JM, McKearn JP. Monoclonal antibodies specific for novel murine cell surface markers define subpopulations of germinal center cells. Cell Immunol. 1992 Sep;143(2):449-66. doi: 10.1016/0008-8749(92)90039-r. PMID: 1511484". Cellular Immunology. 143 (2): 449–466. doi:10.1016/0008-8749(92)90039-r. PMID 1511484.
  6. ^ Platt, Frances; Walkley, Steven, eds. (2004). "Platt, Frances, and Steven Walkley (eds), Lysosomal Disorders of the Brain: Recent Advances in Molecular and Cellular Pathogenesis and Treatment (Oxford, 2004; online edn, Oxford Academic, 1 Sept. 2009)". doi.org/10.1093/acprof:oso/9780198508786.001.0001. doi:10.1093/acprof:oso/9780198508786.001.0001. ISBN 0-19-850878-6.
  7. ^ Platt, F. M.; Neises, G. R.; Dwek, R. A.; Butters, T. D. (1994). "F.M. Platt, G.R. Neises, R.A. Dwek, and T.D. Butters (1994) N-butyldeoxynojirimycin is a novel inhibitor of glycolipid biosynthesis J. Biol. Chem. 269, 8362-8365, PMID: 7929454". The Journal of Biological Chemistry. 269 (11): 8362–8365. doi:10.1016/S0021-9258(17)37202-2. PMID 8132559.
  8. ^ Platt, F. M.; Neises, G. R.; Karlsson, G. B.; Dwek, R. A.; Butters, T. D. (1994). "F.M. Platt, G. R. Neises, G. B. Karlsson, R. A. Dwek and T. D. Butters (1994) N-Butyldeoxygalactonojirimycin inhibits glycolipid biosynthesis but does not affect N-linked oligosaccharide processing. J. Biol. Chem.269, 27108-27114, PMID: 7929454". The Journal of Biological Chemistry. 269 (43): 27108–27114. doi:10.1016/S0021-9258(18)47132-3. PMID 7929454.
  9. ^ Platt, F. M.; Neises, G. R.; Reinkensmeier, G.; Townsend, M. J.; Perry, V. H.; Proia, R. L.; Winchester, B.; Dwek, R. A.; Butters, T. D. (1997). "9. Platt, F. M., Neises, G.R., Reinkensmeier,G., Townsend, M.J., Perry, V.H., Proia, R.L., Winchester, B., Dwek, R.A. and Butters, T.D. (1997) Prevention of lysosomal storage in Tay-Sachs mice treated with N-butyldeoxynojirimycin. Science, 276, 428-431. PMID: 9103204". Science. 276 (5311): 428–431. doi:10.1126/science.276.5311.428. PMID 9103204.
  10. ^ Jeyakumar, M.; Butters, T. D.; Cortina-Borja, M.; Hunnam, V.; Proia, R. L.; Perry, V. H.; Dwek, R. A.; Platt, F. M. (1999). "Jeyakumar, M., Butters, T.D., Cortina-Borja, M., Proia, R.L., Hunnam, V., Perry, V.H., Dwek, R.A. and Platt, F.M. (1999) Delayed symptom onset and increased life expectancy in Sandhoff disease mice treated with N-butyldeoxynojirimycin. Proc. Natl. Acad. Sci. U.S.A., 96, 6388-6393. PMID: 10339597". Proceedings of the National Academy of Sciences of the United States of America. 96 (11): 6388–6393. doi:10.1073/pnas.96.11.6388. PMC 26891. PMID 10339597.
  11. ^ Cox, T.; Lachmann, R.; Hollak, C.; Aerts, J.; Van Weely, S.; Hrebícek, M.; Platt, F.; Butters, T.; Dwek, R.; Moyses, C.; Gow, I.; Elstein, D.; Zimran, A. (2000). "Cox, T.M., Lachmann, R.H., Hollak, C.E.M., Aerts, J.M.F.G., van Weely, S., Hrebicek, M., Platt, F.M., Butters, T.D., Dwek, R.A., Moyses, C., Gow, I.R., Elstein, D. and Zimran, A. (2000) Novel oral treatment of Gaucher's disease with N-butyldeoxynojirmicin (OGT 918) to decrease substrate biosynthesis. Lancet. 355, 1481-1485. PMID: 10801168". The Lancet. 355 (9214): 1481–1485. doi:10.1016/s0140-6736(00)02161-9. PMID 10801168.
  12. ^ Jeyakumar, M.; Norflus, F.; Tifft, C. J.; Cortina-Borja, M.; Butters, T. D.; Proia, R. L.; Perry, V. H.; Dwek, R. A.; Platt, F. M. (2001). "Jeyakumar, M., Norflus, F., Tifft, C.J., Cortina-Borja, M., Butters, T.D., Proia, R.L., Perry, V.H., Dwek, R.A. and Platt, F.M. (2001) Enhanced Survival in Sandhoff Disease Mice Receiving a Combination of Substrate Deprivation and Bone Marrow Transplantation. Blood. 97, 327-329. PMID: 11133779". Blood. 97 (1): 327–329. doi:10.1182/blood.v97.1.327. PMID 11133779.
  13. ^ Jeyakumar, M.; Thomas, R.; Elliot-Smith, E.; Smith, D. A.; Van Der Spoel, A. C.; d'Azzo, A.; Perry, V. H.; Butters, T. D.; Dwek, R. A.; Platt, F. M. (April 2003). "Jeyakumar, M., Thomas, R., Eliott-Smith, E., van der Spoel, A., d'Azzo, A., Perry, V.H., Butters, T.D., Dwek, RA. and Platt, F.M. (2003) Central nervous system inflammation is a hallmark of pathogenesis in mouse models of GM1 and GM2 gangliosidosis. Brain, 126, 974-987, PMID: 12615653". Brain. 126 (4): 974–987. doi:10.1093/brain/awg089. PMID 12615653.
  14. ^ Simpson, M. A.; Cross, H.; Proukakis, C.; Priestman, D. A.; Neville, D. C.; Reinkensmeier, G.; Wang, H.; Wiznitzer, M.; Gurtz, K.; Verganelaki, A.; Pryde, A.; Patton, M. A.; Dwek, R. A.; Butters, T. D.; Platt, F. M.; Crosby, A. H. (2004). "14. Simpson, M.A., Cross, H., Proukakis, C., Priestman, D.A., Neville. D.C.A., Reinkensmeier, G., Wiznitzer, M., Gurz, K., Verganelaki, A., Pryde, A., Patton, M.A., Dwek, R.A., Butters, T.D., Platt, F.M. and Crosby, A. (2004) Infantile onset epilepsy syndrome caused by homozygous loss of function mutations in GM3 synthase. Nature Genetics 36, 1225-1229, PMID: 15502825". Nature Genetics. 36 (11): 1225–1229. doi:10.1038/ng1460. PMID 15502825.
  15. ^ Lee, J. P.; Jeyakumar, M.; Gonzalez, R.; Takahashi, H.; Lee, P. J.; Baek, R. C.; Clark, D.; Rose, H.; Fu, G.; Clarke, J.; McKercher, S.; Meerloo, J.; Muller, F. J.; Park, K. I.; Butters, T. D.; Dwek, R. A.; Schwartz, P.; Tong, G.; Wenger, D.; Lipton, S. A.; Seyfried, T. N.; Platt, F. M.; Snyder, E. Y. (2007). "Lee, J-P, Jeyakumar, M., Lee, P-I, Gonzalez, R., Takahashi, H., Back, R., Tong, G., Clark, D., Clarke, J., Rose, H., McKercher, S., Muller, F-J., Meerloo, J., Wenger, D., Schwartz, P., Lipton, S.A., Butters, T.D., Dwek, R.A., Park, KI, Seyfried, T.N., Platt, F.M. and Snyder, E.Y. (2007) Stem cells act through multiple mechanisms to benefit mice with neurodegenerative metabolic disease. Nature Medicine, 13, 439-447. PMID: 17351625". Nature Medicine. 13 (4): 439–447. doi:10.1038/nm1548. PMID 17351625.
  16. ^ Speak, A. O.; Salio, M.; Neville, D. C.; Fontaine, J.; Priestman, D. A.; Platt, N.; Heare, T.; Butters, T. D.; Dwek, R. A.; Trottein, F.; Exley, M. A.; Cerundolo, V.; Platt, F. M. (2007). "Speak, AO, Salio, M., Neville, DC, Fontaine, J., Priestman, DA, Platt, N., Heare, T., Butters, TD, Dwek, RA, Trottein, F., Exley, MA, Cerundolo, V. and Platt FM (2007). Implications for iNKT cell ligands due to the restricted presence of isoglobotrihexosylceramide (iGb3) in mammals. Proc. Natl. Acad. Sci. U.S.A. 104, 5971-5976, PMID: 17372214". Proc. Natl. Acad. Sci. U.S.A. 104 (14): 5971–5976. doi:10.1073/pnas.0607285104. PMC 1851601. PMID 17372214.
  17. ^ Porubsky, S.; Speak, A. O.; Luckow, B.; Cerundolo, V.; Platt, F. M.; Gröne, H. J. (2007). "Porubsky, S., Speak, A.O., Lucklow, B., Cerundolo, V., Platt, F.M. and Grone, H-J. (2007) Normal development and function of iNKT cells in mice deficient in isoglobotrihexosylceramide (iGb3). Proc. Natl. Acad. Sci. U.S.A. 104, 5977-5982, PMID: 17372206". Proc. Natl. Acad. Sci. U.S.A. 104 (14): 5977–5982. doi:10.1073/pnas.0611139104. PMC 1851602. PMID 17372206.
  18. ^ D’Angelo, Giovanni; Polishchuk, Elena; Tullio, Giuseppe Di; Santoro, Michele; Campli, Antonella Di; Godi, Anna; West, Gun; Bielawski, Jacek; Chuang, Chia-Chen; van der Spoel, Aarnoud C.; Platt, Frances M.; Hannun, Yusuf A.; Polishchuk, Roman; Mattjus, Peter; De Matteis, Maria Antonietta (September 2007). "Glycosphingolipid synthesis requires FAPP2 transfer of glucosylceramide". Nature. 449 (7158): 62–67. Bibcode:2007Natur.449...62D. doi:10.1038/nature06097. ISSN 1476-4687. PMID 17687330.
  19. ^ Lloyd-Evans, Emyr; Morgan, Anthony J.; He, Xingxuan; Smith, David A.; Elliot-Smith, Elena; Sillence, Daniel J.; Churchill, Grant C.; Schuchman, Edward H.; Galione, Antony; Platt, Frances M. (November 2008). "Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium". Nature Medicine. 14 (11): 1247–1255. doi:10.1038/nm.1876. ISSN 1546-170X. PMID 18953351.
  20. ^ D’Angelo, Giovanni; Uemura, Takefumi; Chuang, Chia-Chen; Polishchuk, Elena; Santoro, Michele; Ohvo-Rekilä, Henna; Sato, Takashi; Di Tullio, Giuseppe; Varriale, Antonio; D’Auria, Sabato; Daniele, Tiziana; Capuani, Fabrizio; Johannes, Ludger; Mattjus, Peter; Monti, Maria (September 2013). "Vesicular and non-vesicular transport feed distinct glycosylation pathways in the Golgi". Nature. 501 (7465): 116–120. Bibcode:2013Natur.501..116D. doi:10.1038/nature12423. ISSN 1476-4687. PMID 23913272.
  21. ^ Harlalka, Gaurav V.; Lehman, Anna; Chioza, Barry; Baple, Emma L.; Maroofian, Reza; Cross, Harold; Sreekantan-Nair, Ajith; Priestman, David A.; Al-Turki, Saeed; McEntagart, Meriel E.; Proukakis, Christos; Royle, Louise; Kozak, Radoslaw P.; Bastaki, Laila; Patton, Michael (December 2013). "Mutations in B4GALNT1 (GM2 synthase) underlie a new disorder of ganglioside biosynthesis". Brain. 136 (12): 3618–3624. doi:10.1093/brain/awt270. ISSN 1460-2156. PMC 3859217. PMID 24103911.
  22. ^ Vruchte, Danielle te; Speak, Anneliese O.; Wallom, Kerri L.; Eisa, Nada Al; Smith, David A.; Hendriksz, Christian J.; Simmons, Louise; Lachmann, Robin H.; Cousins, Alison; Hartung, Ralf; Mengel, Eugen; Runz, Heiko; Beck, Michael; Amraoui, Yasmina; Imrie, Jackie (2014-03-03). "Relative acidic compartment volume as a lysosomal storage disorder–associated biomarker". The Journal of Clinical Investigation. 124 (3): 1320–1328. doi:10.1172/JCI72835. ISSN 0021-9738. PMC 3934186. PMID 24487591.
  23. ^ Kirkegaard, Thomas; Gray, James; Priestman, David A.; Wallom, Kerri-Lee; Atkins, Jennifer; Olsen, Ole Dines; Klein, Alexander; Drndarski, Svetlana; Petersen, Nikolaj H. T.; Ingemann, Linda; Smith, David A.; Morris, Lauren; Bornæs, Claus; Jørgensen, Signe Humle; Williams, Ian (2016-09-07). "Heat shock protein–based therapy as a potential candidate for treating the sphingolipidoses". Science Translational Medicine. 8 (355): 355ra118. doi:10.1126/scitranslmed.aad9823. PMC 6821533. PMID 27605553.
  24. ^ Fineran, Paul; Lloyd-Evans, Emyr; Lack, Nathan A.; Platt, Nick; Davis, Lianne C.; Morgan, Anthony J.; Höglinger, Doris; Tatituri, Raju Venkata V.; Clark, Simon; Williams, Ian M.; Tynan, Patricia; Al Eisa, Nada; Nazarova, Evgeniya; Williams, Ann; Galione, Antony; Ory, Daniel S.; Besra, Gurdyal S.; Russell, David G.; Brenner, Michael B.; Sim, Edith; Platt, Frances M. (2017). "Pathogenic mycobacteria achieve cellular persistence by inhibiting the Niemann-Pick Type C disease cellular pathway". Wellcome Open Research. 1: 18. doi:10.12688/wellcomeopenres.10036.2. PMC 5172425. PMID 28008422.
  25. ^ Höglinger, D.; Burgoyne, T.; Sanchez-Heras, E.; Hartwig, P.; Colaco, A.; Newton, J.; Futter, C. E.; Spiegel, S.; Platt, F. M.; Eden, E. R. (2019-09-19). "NPC1 regulates ER contacts with endocytic organelles to mediate cholesterol egress". Nature Communications. 10 (1): 4276. Bibcode:2019NatCo..10.4276H. doi:10.1038/s41467-019-12152-2. ISSN 2041-1723. PMC 6753064. PMID 31537798.
  26. ^ "Our Scientists | IntraBio". IntraBio | biopharmaceutical research and development. 2018-04-20. Retrieved 2024-12-11.
  27. ^ "AQNEURSA™ (levacetylleucine) NowApproved & Available". aqneursa. Retrieved 2024-12-11.
  28. ^ Williams I, Pandey S, Haller W, Huynh HQ, Chan A, Düeker G, Bettels R, Peyrin-Biroulet L, Dike CR, DeGeeter C, Smith D, Al Eisa N, Platt N, Marquardt T, Schwerd T, Platt FM, Uhlig HH (2022). "Anti-TNF therapy for inflammatory bowel disease in patients with neurodegenerative Niemann-Pick disease Type C." Wellcome Open Research. 7: 11. doi:10.12688/wellcomeopenres.16986.1. PMC 9171292. PMID 35694196.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  29. ^ Gray, James; Fernández-Suárez, María E.; Falah, Maysa; Smith, David; Smith, Claire; Kaya, Ecem; Palmer, Ashley M.; Fog, Cathrine K.; Kirkegaard, Thomas; Platt, Frances M. (2022-12-01). "Heat shock protein amplification improves cerebellar myelination in the Npc1nih mouse model". eBioMedicine. 86. doi:10.1016/j.ebiom.2022.104374. ISSN 2352-3964. PMC 9713282. PMID 36455410.
  30. ^ Durán, Anyelo; Priestman, David A.; Las Heras, Macarena; Rebolledo-Jaramillo, Boris; Olguín, Valeria; Calderón, Juan F.; Zanlungo, Silvana; Gutiérrez, Jaime; Platt, Frances M.; Klein, Andrés D. (January 2023). "A Mouse Systems Genetics Approach Reveals Common and Uncommon Genetic Modifiers of Hepatic Lysosomal Enzyme Activities and Glycosphingolipids". International Journal of Molecular Sciences. 24 (5): 4915. doi:10.3390/ijms24054915. ISSN 1422-0067. PMC 10002577. PMID 36902345.
  31. ^ Chen OCW, Siebel S, Colaco A, Nicoli ER, Platt N, Shepherd D, Newman S, Armitage AE, Farhat NY, Seligmann G, Smith C, Smith DA, Abdul-Sada A, Jeyakumar M, Drakesmith H, Porter FD, Platt FM (2023). "Defective iron homeostasis and hematological abnormalities in Niemann-Pick disease type C1". Wellcome Open Research. 7: 267. doi:10.12688/wellcomeopenres.17261.2. PMC 10090865. PMID 37065726.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  32. ^ Platt, Frances M. (2023-10-16). "The expanding boundaries of sphingolipid lysosomal storage diseases; insights from Niemann–Pick disease type C". Biochemical Society Transactions. 51 (5): 1777–1787. doi:10.1042/BST20220711. ISSN 0300-5127. PMC 10657176. PMID 37844193.
  33. ^ Duffy, Hannah B. D.; Byrnes, Colleen; Zhu, Hongling; Tuymetova, Galina; Lee, Y. Terry; Platt, Frances M.; Proia, Richard L. (2024-11-08). "Deletion of Gba in neurons, but not microglia, causes neurodegeneration in a Gaucher mouse model". JCI Insight. 9 (21). doi:10.1172/jci.insight.179126. ISSN 0021-9738. PMC 11601582. PMID 39312723.
  34. ^ Wallom, Kerri-Lee; Fernández-Suárez, María E.; Priestman, David A.; te Vruchte, Danielle; Huebecker, Mylene; Hallett, Penelope J.; Isacson, Ole; Platt, Frances M. (2022-02-01). "Glycosphingolipid metabolism and its role in ageing and Parkinson's disease". Glycoconjugate Journal. 39 (1): 39–53. doi:10.1007/s10719-021-10023-x. ISSN 1573-4986. PMC 8979855. PMID 34757540.
  35. ^ "Alan Gordon award". www.gaucher.org.uk. Retrieved 2024-12-11.
  36. ^ a b "Academy of Europe: Platt Frances Mary". www.ae-info.org. Retrieved 2024-12-11.
  37. ^ "Professor Frances Platt". acmedsci.ac.uk. Retrieved 2024-12-11.
  38. ^ "Frances Platt receives Royal Society Wolfson Research Merit Award | Merton College - Oxford". www.merton.ox.ac.uk. Retrieved 2024-12-11.
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