Our lab’s research interests lie in understanding molecular mechanisms that underlie host-pathogen interactions during viral disease, with a focus on key global pathogens like Influenza A virus (IAV) and SARS-CoV-2. We are specifically interested in the following two questions.
(1) How do infection-induced alterations in splicing and translation dictate host-viral interactions?
Host-viral interactions are often studied in the context of “reference” transcripts and genes. However, there remains a rich diversity of “non-reference” alternatively-spliced or alternatively-translated, infection-specific transcripts and proteins that we still do not fully understand. We are interested in identifying and further understanding how these infection-specific transcripts/proteins come about and how they contribute to infection outcomes.
(2) How do infection-induced changes to the host epigenome dictate short- and long-term infection outcomes?
During infection, the host chromatin environment is altered as a consequence of viral-induced signal transduction events. We are interested in understanding what host and viral factors contribute to these changes, as well as how these changes impact the host and host organism in the long run.
Selected Publications (For full list: Google scholar)
Generation of host-directed and virus-specific antivirals using targeted protein degradation promoted by small molecules and viral RNA mimics. Cell Host Microbe (2023) *co-first author
Zhao N*, Ho JS*, Meng F*, Zheng S, Kurland AP, Tian L, Rea-Moreno M, Song X, Seo J-S, Kaniskan HÜ, Te Velthuis AJW, Tortorella D, Chen Y-W, Johnson JR, Jin J, Marazzi I.
Topoisomerase 1 inhibition therapy 1 protects against SARS-CoV-2 induced lethal inflammation.
Cell (2021) *co-first author Ho JS*, Mok BW*, Campisi L, Jordan T, Yildiz S, Parameswaran S, Wayman JA, Gaudreault NN, Meekins DA, Indran SV, Morozov I, Trujillo JD, Fstkchyan YS, Rathnasinghe R, Zhu Z, Zheng S, Zhao N, White K, Ray-Jones H, Malysheva V, Thiecke MJ, Lau SY, Liu H, Junxia Zhang A, Chak-Yiu Lee A, Liu WC, Aydillo T, Salom Melo B, Guccione E, Sebra R, Shum E, Bakker J, Kaufman DA, Moreira AL, Carossino M, Balasuriya UBR, Byun M, Miraldi ER, Albrecht RA, Schotsaert M, Garcia-Sastre A, Chanda SK, Jeyasekharan AD, TenOever BR, Spivakov M, Weirauch MT, Heinz S, Chen H, Benner C, Richt JA, Marazzi I.
Hybrid gene origination creates human-virus chimeric proteins during infection.(2020) Cell *co-first author
Ho JS*, Angel M*, Ma Y*, Sloan E*, Wang GJ, Martinez-Romero C, Alenquer M, Roudko V, Chung L, Zheng S, Chang M, Fstkchyan Y, Clohisey S, Dinan AM, Gibbs J, Gifford R, Shen R, Gu Q, Irigoyen N, Campisi L, Huang C, Zhao N, Jones JD, van Knippenberg I, Zhu Z, Moshkina N, Meyer L, Noel J, Peralta Z, Rezelj V, Kaake R, Rosenberg B, Wang B, Wei J, Paessler S, Wise HM, Johnson J, Vannini A, Amorim MJ, Baillie JK, Miraldi ER, Benner C, Brierley I, Digard P, Łuksza M, Firth AE, Krogan N, Greenbaum BD, MacLeod MK, van Bakel H, Garcìa-Sastre A, Yewdell JW, Hutchinson E and Marazzi I.
Unconventional Viral Gene Expression Mechanisms as Therapeutic Targets.
Nature (2021) *co-first author Ho JS*, Zhu Z*, Marazzi I.
Emergency drug use in a pandemic: harsh lessons from COVID-19.
Cell (2021) Cross G, Ho JS, Zacharias W, Jeyasekharan AD, Marazzi I
HNRNPM controls circRNA biogenesis and splicing fidelity to sustain prostate cancer cell fitness.
ELife (2021) Ho JS, Low D, Schwarz M, Incarnato D, Gay F, Tabaglio T, Zhang JX, Wollman H, Chen L, An O, Chan THM, Hickman AH, Zheng S, Roudko V, Chen S, Ahmed M, He HH, Greenbaum BD, Marazzi I, Serresi M, Gargiulo G, Oliviero S, Wee DKB, Guccione E.
Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation.
Science. (2016) Rialdi A, Campisi L, Zhao N, Lagda AC, Pietzsch C, Ho JS, Martinez-Gil L, Fenouil R, Chen X, Edwards M, Metreveli G, Jordan S, Peralta Z, Munoz-Fontela C, Bouvier N, Merad M, Jin J, Weirauch M, Heinz S, Benner C, van Bakel H, Basler C, García-Sastre A, Bukreyev A, Marazzi I.
Senataxin suppresses the antiviral transcriptional response and controls viral biogenesis.
Nat Immunol. (2015) *co-first author Miller MS*, Rialdi A*, Ho JS*, Tilove M, Martinez-Gil L, Moshkina NP, Peralta Z, Noel J, Melegari C, Maestre AM, Mitsopoulos P, Madrenas J, Heinz S, Benner C, Young JA, Feagins AR, Basler CF, Fernandez-Sesma A, Becherel OJ, Lavin MF, van Bakel H, Marazzi I.
The "histone mimicry" by pathogens.
Cold Spring Harb Symp Quant Biol. (2013) *Equal contributing author Schaefer U*, Ho JS*, Prinjha RK, Tarakhovsky A.
Suppression of the antiviral response by an influenza histone mimic
Nature (2012) Marazzi I, Ho JS, Kim J, Manicassamy B, Dewell S, Albrecht RA, Seibert CW, Schaefer U, Jeffrey KL, Prinjha RK, Lee K, García-Sastre A, Roeder RG, Tarakhovsky A.