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Ana Maria Cuervo

From Wikipedia, the free encyclopedia
Ana Maria Cuervo
Ana Maria Cuervo in 2008
Born (1966-07-14) July 14, 1966 (age 60)
Barcelona, Spain
OccupationsScientist, cell biologist
Known forChaperone-mediated autophagy research
WebsiteResearch lab

Ana Maria Cuervo (born 14 July 1966) is a Spanish-American physician, researcher, and cell biologist. She is a distinguished professor in developmental and molecular biology and medicine and co-director of the Institute for Geroscience at the Albert Einstein College of Medicine. She is best known for her research work on autophagy, the process by which cells recycle waste products, and its changes in aging and age-related diseases.

Biography

[edit]

Cuervo was born in Barcelona, Spain, on 14 July 1966. She studied medicine at the University of Valencia in 1986 and further pursued a PhD in biochemistry and molecular biology under the mentorship of Erwin Knecht, a biochemist studying lysosomes and proteosome at the time.[1] In 1993, she published her first academic paper as a co-author on lysosomal degradation which challenged the assumption that it was non-specific.[2] Cuervo also worked with Fred “Paulo” Dice of Tufts University on lysosomes during the summer months as Spanish labs were closed during this time of year. Cuervo later accepted a full-time post-doctorate position at Dice's laboratory and focused on understanding this selective lysosomal degradation pathway. From 1994 to 2000, Cuervo and Dice published their findings on this pathway, identified the lysosomal membrane protein LAMP2A as the receptor for this form of autophagy and termed it chaperone-mediated autophagy (CMA).[3][4]

In October 2001, Cuervo accepted a faculty position at the Albert Einstein College of Medicine in The Bronx, New Yorkwhere she continues primarily focused on chaperone-mediated autophagy and its role in aging and human disease.

Academic and scientific activities

[edit]

Cuervo is the co-director of the Einstein Institute for Aging Research and a member of the Einstein Liver Research Center and Cancer Center. She is also the Robert and Renée Belfer Chair for the Study of Neurodegenerative Diseases at Albert Einstein College of Medicine. In 2015 she was elected International Academic of the Royal Academy of Medicine of the Valencia Community, in 2017 member of the Real Academia de Ciencias Exactas, Fisicas y Naturales and in 2021 member of the Royal Academy of Farmacy in Spain. Dr. Cuervo is also one of the funding members of the Academy of Geroscience. In 2018, Cuervo was elected a member of the American Academy of Arts and Sciences[5] and in 2019 to the National Academy of Sciences.

She has also served as a member of the National Institute on Aging (NIA) Scientific Council, NIH Scientific Council of Councils, NIA Board of Scientific Counselors and in the Advisory Committee to the NIH Deputy Director.[6] Dr. Cuervo is also one of the founding members of the Women in Autophagy (WIA) network dedicate to promote careers of young scientist interested in autophagy.

Cuervo was co-editor-in-chief of the Aging Cell journal from 2007 until 2021 and serves in the editorial board of Cell Metabolism, Molecular Cell, PNAS and Geromedicine.[7] She has been involved in more than 300 publications.[8] Dr. Cuervo has been included in the 2018, 2019, 2020 Highly Cited Researchers List (ranking of top 1% cited researchers).

Research

[edit]

Her research lab focused on protein translocations across lysosomal membranes, identifying regulator proteins like glial fibrillary acidic protein[9] or the mTORC2-Akt-Phlpp axis[10]. In collaboration with neuroscientist David Sulzer of Columbia University Medical Center, she published early evidence of altered CMA in Parkinson's disease.[11] and Huntington Disease.[12] Cuervo's research team also identified LRRK2, a protein enzyme that becomes mutated in Parkinson's disease, disrupts the process of translocation across lysosomal membranes.[13][1] The work of her group expanded later to tauopathies, including Alzheimer's Disease, where they found that the pathogenic variants of tau exert an inhibitory effect on CMA and that genetic and pharmacological upregulation of CMA in mouse models of tauopathies reduces pathology, preserves memory and learning and ameliorates disease progression.[14] [15][16]

Beyond the central nervous system, her group has undertaken a systematic approach to explore changes in CMA with age at the systemic level and linked those changes to different age-related diseases.[17] They identified the circadian nature of CMA[18] and sex-specific changes in CMA with age in most organs[19]. They demonstrate that CMA contributes to regulation of metabolic cellular processes related to glucose and lipid metabolism[20][21], DNA repair and cell cycle[22], and cell activation and differentiation[23][24][25]. Cuervo's group has demonstrated malfunctioning of autophagy in neurodegenerative diseases[26], age-related sarcopenia[27], atherosclerosis, immune senescence[28], eye disorders [29][30], and in cancer[31].

As part of Cuervo's interest on the selectivity of autophagy, her group co-discovered with Mark Czaja and Rajat Sign the process of lipophagy[32], which selectively mobilizes lipid droplets through autophagy, and with Laura Santambrogio co-discovered endosomal microautophagy (e-MI)[33], a selective mechanism for internalization of proteins into late endosomes/multivesicular bodies. Later Cuervo's group showed that e-MI cross-talks with CMA[34] and that, as it is the case for CMA, eMI activity also declines with age[35].

Recognition

[edit]

Cuervo and her team have received numerous awards including the P. Benson Award, Keith Porter Fellow, Nathan Shock Memorial Award, Vincent Cristofalo Award in Aging, Bennett J. Cohen, Marshall Horwitz Prize, the Saul Korey Prize in Translational Medicine, the Juan Negrin Award on Physiology, the Spirit of Achievement Award, the SFRR-E Annual Award and the Howard Taylor Ricketts Prize. She has delivered prominent lectures such as the Robert R. Konh, the NIH Director’s, the Roy Walford, the Feodor Lynen, the Margaret Pittman, the IUBMB, the David H. Murdoxk, the Gerry Aurbach , the SEBBM L’Oreal-UNESCO for Women in Science, the Ronal Kohn, and the Harvey Lecture. She also received three times the LaDonne Schulman Teaching Award .[36] In 2023, Cuervo was awarded Doctor Honoris Causa from the University of Buenos Aires. She was elected to the National Academy of Sciences in 2019.[37]

Personal life

[edit]

Cuervo's husband was Dr. Fernando Macian, an immunologist at Albert Einstein College of Medicine, who sadly passed away in 2023. Cuervo and Macian were together since they met first year of Medical School in a research lab and continue collaborating scientifically through the years.[38]

References

[edit]
  1. 1 2 SCUDELLARI, MEGAN (1 November 2013). "Waste-Management Consultant". The Scientist Magazine®. Retrieved 27 July 2018.
  2. ↑ Aniento, F; Roche, E; Cuervo, AM; Knecht, E (15 May 1993). "Uptake and degradation of glyceraldehyde-3-phosphate dehydrogenase by rat liver lysosomes". The Journal of Biological Chemistry. 268 (14): 10463–70. doi:10.1016/S0021-9258(18)82222-0. PMID 8486700.
  3. ↑ Cuervo, A. M.; Dice, J. F. (1996-07-26). "A receptor for the selective uptake and degradation of proteins by lysosomes". Science. 273 (5274): 501–503. Bibcode:1996Sci...273..501C. doi:10.1126/science.273.5274.501. ISSN 0036-8075. PMID 8662539. S2CID 42850597.
  4. ↑ Cuervo, Ana Maria; Dice, J. Fred (6 October 2000). "Age-related Decline in Chaperone-mediated Autophagy". Journal of Biological Chemistry. 275 (40): 31505–31513. doi:10.1074/jbc.M002102200. ISSN 0021-9258. PMID 10806201.
  5. ↑ "Ana Maria Cuervo, M.D., Ph.D., is Elected to the American Academy of Arts and Sciences". Albert Einstein College of Medicine. Archived from the original on 28 July 2018. Retrieved 28 July 2018.
  6. ↑ "Ana Maria Cuervo MD, PhD". The Michael J. Fox Foundation for Parkinson's Research. Retrieved 28 July 2018.
  7. ↑ "Ana Maria Cuervo, Ph.D, M.D". Einstein Experts for Media. Albert Einstein College of Medicine. Archived from the original on 28 July 2018. Retrieved 26 July 2018.
  8. ↑ "Ana Maria Cuervo, Ph.D., M.D. – Publications". einstein.pure.elsevier.com. Elsevier. Retrieved 28 July 2018.
  9. ↑ Bandyopadhyay, U; Sridhar, S; Kaushik, S; Kiffin, R; Cuervo, AM (27 August 2010). "Identification of regulators of chaperone-mediated autophagy". Molecular Cell. 39 (4): 535–47. doi:10.1016/j.molcel.2010.08.004. PMC 2945256. PMID 20797626.
  10. ↑ Arias, Esperanza; Koga, Hiroshi; Diaz, Antonio; Mocholi, Enric; Patel, Bindi; Cuervo, Ana María (2015-07-16). "Lysosomal mTORC2/PHLPP1/Akt Regulate Chaperone-Mediated Autophagy". Molecular Cell. 59 (2): 270–284. doi:10.1016/j.molcel.2015.05.030. ISSN 1097-4164. PMC 4506737. PMID 26118642.
  11. ↑ Cuervo, AM; Stefanis, L; Fredenburg, R; Lansbury, PT; Sulzer, D (27 August 2004). "Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy". Science. 305 (5688): 1292–5. Bibcode:2004Sci...305.1292C. doi:10.1126/science.1101738. PMID 15333840. S2CID 84928456.
  12. ↑ Martinez-Vicente, M; Talloczy, Z; Wong, E; Tang, G; Koga, H; Kaushik, S; de Vries, R; Arias, E; Harris, S; Sulzer, D; Cuervo, AM (May 2010). "Cargo recognition failure is responsible for inefficient autophagy in Huntington's disease". Nature Neuroscience. 13 (5): 567–76. doi:10.1038/nn.2528. PMC 2860687. PMID 20383138.
  13. ↑ Orenstein, SJ; Kuo, SH; Tasset, I; Arias, E; Koga, H; Fernandez-Carasa, I; Cortes, E; Honig, LS; Dauer, W; Consiglio, A; Raya, A; Sulzer, D; Cuervo, AM (April 2013). "Interplay of LRRK2 with chaperone-mediated autophagy". Nature Neuroscience. 16 (4): 394–406. doi:10.1038/nn.3350. PMC 3609872. PMID 23455607.
  14. ↑ Bourdenx, Mathieu; Martín-Segura, Adrián; Scrivo, Aurora; Rodriguez-Navarro, Jose A.; Kaushik, Susmita; Tasset, Inmaculada; Diaz, Antonio; Storm, Nadia J.; Xin, Qisheng; Juste, Yves R.; Stevenson, Erica; Luengo, Enrique; Clement, Cristina C.; Choi, Se Joon; Krogan, Nevan J. (2021-05-13). "Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome". Cell. 184 (10): 2696–2714.e25. doi:10.1016/j.cell.2021.03.048. ISSN 1097-4172. PMC 8152331. PMID 33891876.
  15. ↑ Caballero, Benjamin; Bourdenx, Mathieu; Luengo, Enrique; Diaz, Antonio; Sohn, Peter Dongmin; Chen, Xu; Wang, Chao; Juste, Yves R.; Wegmann, Susanne; Patel, Bindi; Young, Zapporah T.; Kuo, Szu Yu; Rodriguez-Navarro, Jose Antonio; Shao, Hao; Lopez, Manuela G. (2021-04-14). "Acetylated tau inhibits chaperone-mediated autophagy and promotes tau pathology propagation in mice". Nature Communications. 12 (1): 2238. Bibcode:2021NatCo..12.2238C. doi:10.1038/s41467-021-22501-9. ISSN 2041-1723. PMC 8047017. PMID 33854069.
  16. ↑ Khawaja, Rabia R.; Griego, Ernesto; Lindenau, Kristen; Salek, Asma; Gambardella, Jessica; Scrivo, Aurora; Monday, Hannah R.; Bourdenx, Mathieu; Madero-Pérez, Jesús; Khan, Zohaib N.; Chavda, Bhakti; Cutler, Ronald; Graff, Sarah; Sidoli, Simone; Santulli, Gaetano (October 2025). "Chaperone-mediated autophagy regulates neuronal activity by sex-specific remodelling of the synaptic proteome". Nature Cell Biology. 27 (10): 1688–1707. doi:10.1038/s41556-025-01771-1. ISSN 1476-4679. PMC 13539424. PMID 41087566.
  17. ↑ Kaushik, Susmita; Tasset, Inmaculada; Arias, Esperanza; Pampliega, Olatz; Wong, Esther; Martinez-Vicente, Marta; Cuervo, Ana Maria (December 2021). "Autophagy and the hallmarks of aging". Ageing Research Reviews. 72 101468. doi:10.1016/j.arr.2021.101468. ISSN 1872-9649. PMC 8616816. PMID 34563704.
  18. ↑ Juste, Yves R.; Kaushik, Susmita; Bourdenx, Mathieu; Aflakpui, Ranee; Bandyopadhyay, Sanmay; Garcia, Fernando; Diaz, Antonio; Lindenau, Kristen; Tu, Vincent; Krause, Gregory J.; Jafari, Maryam; Singh, Rajat; Muñoz, Javier; Macian, Fernando; Cuervo, Ana Maria (December 2021). "Reciprocal regulation of chaperone-mediated autophagy and the circadian clock". Nature Cell Biology. 23 (12): 1255–1270. doi:10.1038/s41556-021-00800-z. ISSN 1476-4679. PMC 8688252. PMID 34876687.
  19. ↑ Khawaja, Rabia R.; Martín-Segura, Adrián; Santiago-Fernández, Olaya; Sereda, Rebecca; Lindenau, Kristen; McCabe, Mericka; Macho-González, Adrián; Jafari, Maryam; Scrivo, Aurora; Gomez-Sintes, Raquel; Chavda, Bhakti; Saez-Ibanez, Ana Rosa; Tasset, Inmaculada; Arias, Esperanza; Xie, Xianhong (April 2025). "Sex-specific and cell-type-specific changes in chaperone-mediated autophagy across tissues during aging". Nature Aging. 5 (4): 691–708. doi:10.1038/s43587-024-00799-6. ISSN 2662-8465. PMC 12003181. PMID 39910244.
  20. ↑ Schneider, Jaime L.; Suh, Yousin; Cuervo, Ana Maria (2014-09-02). "Deficient chaperone-mediated autophagy in liver leads to metabolic dysregulation". Cell Metabolism. 20 (3): 417–432. doi:10.1016/j.cmet.2014.06.009. ISSN 1932-7420. PMC 4156578. PMID 25043815.
  21. ↑ Kaushik, Susmita; Cuervo, Ana Maria (June 2015). "Degradation of lipid droplet-associated proteins by chaperone-mediated autophagy facilitates lipolysis". Nature Cell Biology. 17 (6): 759–770. Bibcode:2015NaCB...17..759K. doi:10.1038/ncb3166. ISSN 1476-4679. PMC 4449813. PMID 25961502.
  22. ↑ Park, Caroline; Suh, Yousin; Cuervo, Ana Maria (2015-04-16). "Regulated degradation of Chk1 by chaperone-mediated autophagy in response to DNA damage". Nature Communications. 6 6823. Bibcode:2015NatCo...6.6823P. doi:10.1038/ncomms7823. ISSN 2041-1723. PMC 4400843. PMID 25880015.
  23. ↑ Kaushik, Susmita; Juste, Yves R.; Lindenau, Kristen; Dong, Shuxian; Macho-González, Adrián; Santiago-Fernández, Olaya; McCabe, Mericka; Singh, Rajat; Gavathiotis, Evripidis; Cuervo, Ana Maria (2022-11-18). "Chaperone-mediated autophagy regulates adipocyte differentiation". Science Advances. 8 (46) eabq2733. Bibcode:2022SciA....8.2733K. doi:10.1126/sciadv.abq2733. ISSN 2375-2548. PMC 9668314. PMID 36383673.
  24. ↑ Dong, Shuxian; Wang, Qian; Kao, Yun-Ruei; Diaz, Antonio; Tasset, Inmaculada; Kaushik, Susmita; Thiruthuvanathan, Victor; Zintiridou, Aliona; Nieves, Edward; Dzieciatkowska, Monika; Reisz, Julie A.; Gavathiotis, Evripidis; D'Alessandro, Angelo; Will, Britta; Cuervo, Ana Maria (March 2021). "Chaperone-mediated autophagy sustains haematopoietic stem-cell function". Nature. 591 (7848): 117–123. Bibcode:2021Natur.591..117D. doi:10.1038/s41586-020-03129-z. ISSN 1476-4687. PMC 8428053. PMID 33442062.
  25. ↑ Valdor, Rut; Mocholi, Enric; Botbol, Yair; Guerrero-Ros, Ignacio; Chandra, Dinesh; Koga, Hiroshi; Gravekamp, Claudia; Cuervo, Ana Maria; Macian, Fernando (November 2014). "Chaperone-mediated autophagy regulates T cell responses through targeted degradation of negative regulators of T cell activation". Nature Immunology. 15 (11): 1046–1054. doi:10.1038/ni.3003. ISSN 1529-2916. PMC 4208273. PMID 25263126.
  26. ↑ Fleming, Angeleen; Bourdenx, Mathieu; Fujimaki, Motoki; Karabiyik, Cansu; Krause, Gregory J.; Lopez, Ana; Martín-Segura, Adrián; Puri, Claudia; Scrivo, Aurora; Skidmore, John; Son, Sung Min; Stamatakou, Eleanna; Wrobel, Lidia; Zhu, Ye; Cuervo, Ana Maria (2022-03-16). "The different autophagy degradation pathways and neurodegeneration". Neuron. 110 (6): 935–966. doi:10.1016/j.neuron.2022.01.017. ISSN 1097-4199. PMC 8930707. PMID 35134347.
  27. ↑ Santiago-Fernández, Olaya; Coletto, Luisa; Tasset, Inmaculada; Kaushik, Susmita; Concepcion, Axel R.; Qaisar, Rizwan; Macho-González, Adrián; Lindenau, Kristen; Diaz, Antonio; Khawaja, Rabia R.; Donega, Stefano; Banskota, Nirad; Ubaida-Mohien, Ceereena; Pharaoh, Gavin; Ahn, Bumsoo (December 2025). "Age-related decline of chaperone-mediated autophagy in skeletal muscle leads to progressive myopathy". Nature Metabolism. 7 (12): 2589–2611. doi:10.1038/s42255-025-01412-9. ISSN 2522-5812. PMC 12727505. PMID 41339969.
  28. ↑ Harrison, Ranee; Gjergjova, Floralba; Pelka, Sandra; Macho-Gonzalez, Adrian; Chavda, Bhakti; Lindenau, Kristen; Gazteluiturri Garcia, Aiara; Khawaja, Rabia R.; Aguilan, Jennifer T.; Sidoli, Simone; Kaushik, Susmita; Botbol, Yair; Cuervo, Ana Maria; Macian, Fernando (2026-05-22). "Chaperone-mediated autophagy is required for regulatory T cell function". Nature Communications. 17 (1): 6744. Bibcode:2026NatCo..17.6744H. doi:10.1038/s41467-026-73417-1. ISSN 2041-1723. PMC 13385378. PMID 42173902.
  29. ↑ Gómez-Sintes, Raquel; Tasset, Inmaculada; Ramírez-Pardo, Ignacio; Martín-Segura, Adrián; Alonso-Gil, Sandra; Díaz, Antonio; Lindenau, Kristen; Lillo, Concepción; de la Villa, Pedro; Sidoli, Simone; Gavathiotis, Evripidis; Cuervo, Ana María; Boya, Patricia (2026-05-19). "Chaperone-mediated autophagy protects against retinal photoreceptor degeneration by modulating proteostasis of glucose metabolism enzymes". Proceedings of the National Academy of Sciences of the United States of America. 123 (20) e2527503123. Bibcode:2026PNAS..12327503G. doi:10.1073/pnas.2527503123. ISSN 1091-6490. PMC 13187728. PMID 42113991.
  30. ↑ Gomez-Sintes, Raquel; Xin, Qisheng; Jimenez-Loygorri, Juan Ignacio; McCabe, Mericka; Diaz, Antonio; Garner, Thomas P.; Cotto-Rios, Xiomaris M.; Wu, Yang; Dong, Shuxian; Reynolds, Cara A.; Patel, Bindi; de la Villa, Pedro; Macian, Fernando; Boya, Patricia; Gavathiotis, Evripidis (2022-07-21). "Targeting retinoic acid receptor alpha-corepressor interaction activates chaperone-mediated autophagy and protects against retinal degeneration". Nature Communications. 13 (1): 4220. Bibcode:2022NatCo..13.4220G. doi:10.1038/s41467-022-31869-1. ISSN 2041-1723. PMC 9304322. PMID 35864098.
  31. ↑ Arias, Esperanza; Cuervo, Ana Maria (January 2020). "Pros and Cons of Chaperone-Mediated Autophagy in Cancer Biology". Trends in Endocrinology and Metabolism: TEM. 31 (1): 53–66. doi:10.1016/j.tem.2019.09.007. ISSN 1879-3061. PMC 7020649. PMID 31699565.
  32. ↑ Singh, Rajat; Kaushik, Susmita; Wang, Yongjun; Xiang, Youqing; Novak, Inna; Komatsu, Masaaki; Tanaka, Keiji; Cuervo, Ana Maria; Czaja, Mark J. (2009-04-30). "Autophagy regulates lipid metabolism". Nature. 458 (7242): 1131–1135. Bibcode:2009Natur.458.1131S. doi:10.1038/nature07976. ISSN 1476-4687. PMC 2676208. PMID 19339967.
  33. ↑ Sahu, Ranjit; Kaushik, Susmita; Clement, Cristina C.; Cannizzo, Elvira S.; Scharf, Brian; Follenzi, Antonia; Potolicchio, Ilaria; Nieves, Edward; Cuervo, Ana Maria; Santambrogio, Laura (2011-01-18). "Microautophagy of cytosolic proteins by late endosomes". Developmental Cell. 20 (1): 131–139. doi:10.1016/j.devcel.2010.12.003. ISSN 1878-1551. PMC 3025279. PMID 21238931.
  34. ↑ Krause, Gregory J.; Kirchner, Philipp; Stiller, Barbara; Morozova, Kateryna; Diaz, Antonio; Chen, Kuei-Ho; Krogan, Nevan J.; Agullo-Pascual, Esperanza; Clement, Cristina C.; Lindenau, Kristen; Swaney, Danielle L.; Dilipkumar, Shilpa; Bravo-Cordero, Jose Javier; Santambrogio, Laura; Cuervo, Ana Maria (2023-12-26). "Molecular determinants of the crosstalk between endosomal microautophagy and chaperone-mediated autophagy". Cell Reports. 42 (12) 113529. doi:10.1016/j.celrep.2023.113529. ISSN 2211-1247. PMC 10807933. PMID 38060380.
  35. ↑ Krause, Gregory J.; Diaz, Antonio; Jafari, Maryam; Khawaja, Rabia R.; Agullo-Pascual, Esperanza; Santiago-Fernández, Olaya; Richards, Alicia L.; Chen, Kuei-Ho; Dmitriev, Phillip; Sun, Yan; See, Stephanie K.; Abdelmohsen, Kotb; Mazan-Mamczarz, Krystyna; Krogan, Nevan J.; Gorospe, Myriam (October 2022). "Reduced endosomal microautophagy activity in aging associates with enhanced exocyst-mediated protein secretion". Aging Cell. 21 (10) e13713. doi:10.1111/acel.13713. ISSN 1474-9726. PMC 9577956. PMID 36116133.
  36. ↑ "Ana Maria Cuervo, M.D., Ph.D." www.einstein.yu.edu. Albert Einstein College of Medicine. Archived from the original on 3 March 2017. Retrieved 28 July 2018.
  37. ↑ "2019 NAS Election". www.nasonline.org. Archived from the original on April 30, 2019. Retrieved 30 April 2019.
  38. ↑ "Cuervo am macian f - Search Results - PubMed".
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