LIDSKY, Peter V.

Prof. Peter Lidsky received his MS and PhD training in virology at Moscow State University, where his research focused on virus-host interactions in Picornaviruses. He then transitioned to the University of Zurich to develop tools and probes for fluorescent imaging in the Drosophila model. Finally, at the University of California San Francisco (UCSF), he combined his expertise in virology and genetics to build a versatile research program. Notably, at UCSF, he developed the “pathogen control” hypothesis of aging, which forms the foundation of his current research interests.

Research Focus

Our research investigates the intricate link between aging and immunity. Recent scientific evidence suggests a deeper-than-previously-thought interaction between inflammation, cellular senescence, systemic aging, and infections. We are developing the pathogen control hypothesis of aging, which aims to explain these interactions from an evolutionary perspective. This hypothesis challenges the mainstream views that consider aging a result of random damage accumulation. On the contrary, we believe aging is an adaptive, programmed process.

Building on the Hypothesis

Our theoretical framework guides experimental work in both Drosophila and mammals. Currently, the lab focuses on the interplay between viruses and senescent cells. While it was known that viruses can induce cellular senescence and that senescent cells can play an anti-viral role, these mechanisms remain poorly understood. We are testing the “immune militia” hypothesis of cellular senescence. In this model, senescent cells act as “militiamen" recruited from other jobs to defend the organism against infections. These cells are resistant to viruses, produce signaling molecules that enhance resistance in other cells, and communicate with immune cells, the “professional soldiers” of the immune system. Since senescent cells can be detrimental if not cleared promptly by the immune system, we are also investigating whether some long-term complications of viral infections can be explained by virus-induced cellular senescence.

Learn More

Check out Peter’s most recent presentation here:

Editing

Publications

1. Evolution of aging and diseases

2. Lidsky^ PV, Yuan J, Andino^ R. Reconsidering life history theory amid infectious diseases. Trends in Ecology and Evolution. 2023. 38 (8):P699-700.
3. Lidsky^ PV, Andino^ R. Could aging evolve as a pathogen control strategy? Trends in Ecology and Evolution. 2022. 37(12):1046-1057.
4. Lidsky^ PV, Yuan J, Rulison JM, and Andino-Pavlovsky^ R. Is aging an inevitable characteristic of organic life or an evolutionary adaptation? Biochemistry (Moscow). 2022. 87(12): 1777–1817.
5. Lidsky^ PV, Andino^ R. Epidemics as an adaptive driving force determining lifespan setpoints. Proc Natl Acad Sci U S A. 2020. 117(30):17937-17948.
6. Lidsky^ PV, Andino R, Rouzine IM. Variability in viral pathogenesis: modeling the dynamic of acute and persistent infections. Curr Opin Virol. 2017. 23:120-124. PMID: 28551476. PMCID: PMC5695700

7. Virology

8. mRNA-LNP vaccine-induced CD8+ T cells protect mice from lethal SARS-CoV-2 infection in the absence of specific antibodies. Montoya B, Melo-Silva CR, Tang L, Kafle S, Lidsky PV, Bajusz C, Vadovics M, Muramatsu H, Abraham E, Lipinszki Z, Chatterjee D, Scher G, Benitez J, Sung MMH, Tam YK, Catanzaro NJ, Schäfer A, Andino R, Baric RS, Martinez DR, Pardi N, Sigal LJ. Mol Ther. 2024 S1525-0016(24)00236-3.
9. Escoubas CC, Dorman LC, Nguyen PT, Lagares-Linares C, Nakajo H, Anderson SR, Barron JJ, Wade SD, Cuevas B, Vainchtein ID, Silva NJ, Guajardo R, Xiao Y, Lidsky PV, Wang EY, Rivera BM, Taloma SE, Kim DK, Kaminskaya E, Nakao-Inoue H, Schwer B, Arnold TD, Molofsky AB, Condello C, Andino R, Nowakowski TJ, Molofsky AV. Type-I-interferon-responsive microglia shape cortical development and behavior. Cell. 2024 Apr 11;187(8):1936-1954.e24.
10. Aviner R*, PV Lidsky*, Y Xiao, M Tasseto, L Zhang, PL McAlpine, J Elias, J Frydman, R Andino. SARS-CoV-2 Nsp1 regulates translation start site fidelity to promote infection. PLoS Pathogens. 2024. 9;20(2):e1011535.
11. Yang* J, Xiao* Y, Lidsky* PV, Wu C-T, Bonser LR, Peng S, Garcia-Knight MA, Tassetto M, Chung C-I, Li X, Nakayama T, Lee IT, Nayak JV, Ghias K, Shoichet BK, Erle DJ, Jackson PK, Andino R, Shu X. Identifying natural compounds that potently inhibit SARS-CoV-2 in mouse models. Nat. Microbiology. 2023. 8:121–134.
12. Wu* C-T, Lidsky* PV, Xiao* Y, Cheng* R, Lee IT, Nakayama T, Jiang S, He W, Demeter J, Garcia-Knight M, Turn RE, Rojas-Hernandez LS, Ye C, Chiem K, Shon J, Martinez-Sobrido L, Bertozzy CR, Nolan G, Milla C, Nayak JV, Andino R, Jackson PK. SARS-CoV-2 Replication in airway epithelia requires motile cilia and microvillar reprogramming. Cell. 2022. 186(1) 112-130.e20.
13. Wu* C-T, Lidsky* PV, Xiao* Y, Lee* IT, Cheng* R, Nakayama* T, Jiang* S, Demeter J, Bevacqua RJ, Chang CA, Zhu B, Chen H, Goltsev Y, Tzankov A, Nayak JV, Nolan GP, Matter MS, Andino R, Jackson PK. SARS-CoV-2 infects human pancreatic beta-cells and elicits beta-cell impairment, Cell Metabolism. 2021. 33(8):1565-1576.e5.
14. Xiao Y, Lidsky PV, Shirogane Y, Aviner R, Wu C-T, Li W, Zheng W, Talbot D, Catching A, Doitsh G, Su W, Gekko CE, Nayak A, Ernst JD, Brodsky L, Brodsky E, Rousseau E, Capponi S, Bianco S, Nakamura R, Jackson PK, Frydman J, Andino R. A defective viral genome strategy elicits broad protective immunity against respiratory viruses. Cell. 2021. 184(25):6037-6051.e14.
15. Li* X, Lidsky* P, Xiao* Y, Wu C-T, Garcia-Knight M, Yang J, Nakayama T, Nayak JV, Jackson PK, Andino R, Shu X. Ethacridine inhibits SARS-CoV-2 by inactivating viral particles. PLoS Pathogens. 2021. 17(9): e1009898.
16. Deng X, Garcia-Knight MA, Khalid MM, Servellita V, Wang C, Morris MK, Sotomayor-González A, Glasner DR, Reyes KR, Gliwa AS, Reddy NP, San Martin CS, Federman S, Cheng J, Balcerek J, Taylor J, Streithorst JA, Miller S, Sreekumar B, Chen P-Y, Schulze-Gahmen U, Taha TY, Hayashi J, Simoneau CR, Kumar GR, McMahon S, Lidsky PV, Xiao Y, Hemarajata P, Green NM, Espinosa A, Kath C, Haw M, Bell J, Hacker JK, Hanson C, Wadford DA, Anaya C, Ferguson D, Frankino, Haridha Shivram PA, Lareau LF, Wyman SK, Ott M, Andino R, Chiu CY. Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant. Cell. 2021. 184(13):3426-3437.e8.
17. Nakayama T; Lee I; Jiang S; Matter M; Yan C; Overdevest J; Goltsev Y; Shih L-C; Liao C-K; Wu C-T; Zhu B; Zarabanda D; Yang A; Schürch C; Chu P; Chen H; McIlwain D; Borchard N; Gall P; Dholakia S; Xu L; Stalder A; Lidsky PV; Xiao Y; Jackson P; Tai C-J; Yeh T-H; Andino R; Duran J; Mertz K; Patel Z; Haslbauer J; Menter T; Canoll P; DeConde A; Hwang P; Tzankov A; Nolan G; Nayak JV. Determinants of SARS-CoV2-2 entry and replication in airway mucosal tissue and susceptibility in smokers. Cell Reports Medicine. 2021. 2(10):100421.
18. Krupina KA, Sheval EV, Lidsky^ PV. Variability in inhibition of host RNA synthesis by entero- and cardioviruses. J Gen Virol. 2010. 91(Pt 5):1239-44.
19. Lidsky* PV, Romanova* LI, Kolesnikova MS, Bardina MV, Khitrina EV, Hato SV, van Kuppeveld FJ, Agol VI. Interactions between viral and prokaryotic pathogens in a mixed infection with cardiovirus and mycoplasma. J Virol. 2009. 83(19):9940-51. (Current topic in Microbe magazine, Nov 2009).
20. Bardina* MV, Lidsky* PV, Sheval EV, Fominykh KV, van Kuppeveld FJ, Polyakov VY, Agol VI. Mengovirus-induced Rearrangement of the Nuclear Pore Complex: Hijacking Cellular Phosphorylation Machinery. J. Virol. 2009. 83(7):3150-61. (evaluated by F1000).
21. Romanova* LI, Lidsky* PV, Kolesnikova MS, Fominykh KV, Gmyl AP, Sheval EV, Hato S, Van Kuppeveld FJM, Agol VI. Antiapoptotic Activity of the Cardiovirus Leader Protein, a Viral “Security” Protein. J. Virol. 2009. 83(14):7273-84.
22. Lidsky* PV, Hato* S, Bardina* MV, Aminev AG, Palmenberg AC, Sheval EV, Polyakov VY, van Kuppeveld FJ, Agol VI. Nucleocytoplasmic traffic disorder induced by cardioviruses. J Virol. 2006. 80(6):2705-17. (spotlight in JVI, evaluated by F1000).
23. Romanova LI, Belov GA, Lidsky PV, Tolskaya EA, Kolesnikova MS, Evstafieva AG, Vartapetian AB, Egger D, Bienz K, Agol VI. Variability in apoptotic response to poliovirus infection. Virology. 2005. 331(2):292-306.
24. Belov* GA, Lidsky* PV, Mikitas OV, Egger D, Lukyanov KA, Bienz K, Agol VI. Bidirectional increase in permeability of nuclear envelope upon poliovirus infection and accompanying alterations of nuclear pores. J Virol. 2004. 78(18):10166-77.

25. Drosophila genetics and methods development

26. Lidsky PV^, J Yuan, KA Lashkevich, SE Dmitriev, R Andino^. Monitoring integrated stress response in live Drosophila. bioRxiv. 2023.07. 13.548942.
27. Lidsky^ PV, Dmitriev SE, Andino^ R. Introduction of Dicistrovirus IRESes into UAS/SV40-polyA constructs results in premature polyadenylation and strong overexpression of the upstream ORF in Drosophila animals. bioRxiv. 2023.10.04.560905.
28. Lidsky^ PV, Lukyanov KA, Misra T, Handke B, Mishin AS, Lehner CF. A genetically encoded fluorescent probe for imaging of oxygenation gradients in living Drosophila. Development. 2018. 145(4).
29. Nayak A, Kim DY, Trnka MJ, Kerr CH, Lidsky PV, Stanley DJ, Rivera BM, Li KH, Burlingame AL, Jan E, Frydman J, Gross JD, Andino R. A Viral Protein Restricts Drosophila RNAi Immunity by Regulating Argonaute Activity and Stability. Cell Host Microbe. 2018. 24(4):542-557. (evaluated by F1000)
30. Sarkisyan KS, Goryashchenko AS, Lidsky PV, Gorbachev DA, Bozhanova NG, Gorokhovatsky AY, Pereverzeva AR, Ryumina AP, Zherdeva VV, Savitsky AP, Solntsev KM, Bommarius AS, Sharonov GV, Lindquist JR, Drobizhev M, Hughes TE, Rebane A, Lukyanov KA, Mishin AS. Green fluorescent protein with anionic tryptophan-based chromophore and long fluorescence lifetime. Biophys J. 2015. 109(2):380-9.
31. Handke B, Szabad J, Lidsky PV, Hafen E, Lehner CF. Towards long term cultivation of Drosophila wing imaginal discs in vitro. PLoS One. 2014. 9(9):e107333.
32. Lidsky PV, Sprenger F, Lehner CF. Distinct modes of centromere protein dynamics during cell cycle progression in Drosophila S2R+ cells. J Cell Sci. 2013. 126 (20): 4782–4793.

* co-first author, ^ corresponding or co-corresponding author

17 August 2024