Program Official
Guillermo Marquez, Ph.D.

Principal Investigator

Fred R
Hirsch
Awardee Organization

Icahn School Of Medicine At Mount Sinai
United States

Fiscal Year
2022
Activity Code
U54
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date
Notice of Funding Opportunity
NIH RePORTER
For more information, see NIH RePORTER Project 3U54CA260560-02S1

Vulnerability of SARS- CoV-2 Infection in Lung Cancer Based on Serological Antibody Analyses

As a supplement to our existing U54, we propose that Mount Sinai serve as a coordinating site for aggregating and analyzing demographic, clinical and molecular data from multiple lung cancer studies supported by SeroNet. These studies, from prominent institutions across the country, have been investigating the intersection of lung cancer and SARS-CoV-2 to explore the impact of the combined diseases on patient health, investigate the underlying biology that leads to poor outcomes and understand the effects of lung cancer disease and/or treatments on SARS-CoV-2 vaccination-induced immune responses. To accomplish this goal, we will leverage the considerable expertise and experience of the Mount Sinai Bio-informatics group, led by Joseph Finkelstein, and the data analysis capabilities of our partners at the Vanderbilt Department of Statistics.

Publications

  • Rathnasinghe R, Jangra S, Ye C, Cupic A, Singh G, Martínez-Romero C, Mulder LCF, Kehrer T, Yildiz S, Choi A, Yeung ST, Mena I, Gillespie V, De Vrieze J, Aslam S, Stadlbauer D, Meekins DA, McDowell CD, Balaraman V, Corley MJ, Richt JA, De Geest BG, Miorin L, PVI study group, Krammer F, Martinez-Sobrido L, Simon V, García-Sastre A, Schotsaert M, Kleiner G, Saksena M, Srivastava K, Gleason CR, Bermúdez-González MC, Beach KF, Russo KT, Sominsky LA, Ferreri ED, Chernet RL, Eaker LQ, Salimbangon AT, Jurczyszak D, Alshammary H, Mendez WA, Amoako AA, Fabre S, Awawda MH, Shin AS. Characterization of SARS-CoV-2 Spike mutations important for infection of mice and escape from human immune sera. Nature communications. 2022 Jul 7;13(1):3921. PMID: 35798721
  • Babady NE, Burckhardt RM, Krammer F, Moore PL, Enquist LW. Building a Resilient Scientific Network for COVID-19 and Beyond. mBio. 2022 Oct 26;13(5):e0222322. Epub 2022 Sep 20. PMID: 36125317
  • Salem Omar AM, Alam L, Talebi S, García-Sastre A, Narula J, Argulian E. Right Ventricular Abnormality in Patients Hospitalized With COVID-19 Infection During Omicron Variant Surge. The American journal of cardiology. 2022 Jun 15;173:158-160. Epub 2022 Apr 19. PMID: 35459461
  • Escalera A, García-Sastre A, Aydillo T. Protocol to isolate and assess spike protein cleavage in SARS-CoV-2 variants obtained from clinical COVID-19 samples. STAR protocols. 2022 Sep 16;3(3):101502. Epub 2022 Jun 13. PMID: 35776647
  • Rolfo C, Meshulami N, Russo A, Krammer F, García-Sastre A, Mack PC, Gomez JE, Bhardwaj N, Benyounes A, Sirera R, Moore A, Rohs N, Henschke CI, Yankelevitz D, King J, Shyr Y, Bunn PA Jr, Minna JD, Hirsch FR. Lung Cancer and Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Identifying Important Knowledge Gaps for Investigation. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2022 Feb;17(2):214-227. Epub 2021 Nov 10. PMID: 34774792
  • Siddiq MM, Chan AT, Miorin L, Yadaw AS, Beaumont KG, Kehrer T, Cupic A, White KM, Tolentino RE, Hu B, Stern AD, Tavassoly I, Hansen J, Sebra R, Martinez P, Prabha S, Dubois N, Schaniel C, Iyengar-Kapuganti R, Kukar N, Giustino G, Sud K, Nirenberg S, Kovatch P, Albrecht RA, Goldfarb J, Croft L, McLaughlin MA, Argulian E, Lerakis S, Narula J, García-Sastre A, Iyengar R. Functional Effects of Cardiomyocyte Injury in COVID-19. Journal of virology. 2022 Jan 26;96(2):e0106321. Epub 2021 Oct 20. PMID: 34669512
  • Bohan D, Van Ert H, Ruggio N, Rogers KJ, Badreddine M, Aguilar Briseño JA, Elliff JM, Rojas Chavez RA, Gao B, Stokowy T, Christakou E, Kursula P, Micklem D, Gausdal G, Haim H, Minna J, Lorens JB, Maury W. Phosphatidylserine receptors enhance SARS-CoV-2 infection. PLoS pathogens. 2021 Nov 19;17(11):e1009743. doi: 10.1371/journal.ppat.1009743. eCollection 2021 Nov. PMID: 34797899
  • Zhang K, Miorin L, Makio T, Dehghan I, Gao S, Xie Y, Zhong H, Esparza M, Kehrer T, Kumar A, Hobman TC, Ptak C, Gao B, Minna JD, Chen Z, García-Sastre A, Ren Y, Wozniak RW, Fontoura BMA. Nsp1 protein of SARS-CoV-2 disrupts the mRNA export machinery to inhibit host gene expression. Science advances. 2021 Feb 5;7. (6). Print 2021 Feb. PMID: 33547084
  • Wajnberg A, Amanat F, Firpo A, Altman DR, Bailey MJ, Mansour M, McMahon M, Meade P, Mendu DR, Muellers K, Stadlbauer D, Stone K, Strohmeier S, Simon V, Aberg J, Reich DL, Krammer F, Cordon-Cardo C. Robust neutralizing antibodies to SARS-CoV-2 infection persist for months. Science (New York, N.Y.). 2020 Dec 4;370(6521):1227-1230. Epub 2020 Oct 28. PMID: 33115920
  • Kehrer T, García-Sastre A, Miorin L. Control of Innate Immune Activation by Severe Acute Respiratory Syndrome Coronavirus 2 and Other Coronaviruses. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research. 2021 Jun;41(6):205-219. PMID: 34161170
  • Cai H, Chen Y, Feng Y, Asadi M, Kaufman L, Lee K, Kehrer T, Miorin L, Garcia-Sastre A, Gusella GL, Gu L, Ni Z, Mou S, He JC, Zhou W. SARS-CoV-2 viral protein ORF3A injures renal tubules by interacting with TRIM59 to induce STAT3 activation. Molecular therapy : the journal of the American Society of Gene Therapy. 2023 Mar 1;31(3):774-787. Epub 2022 Dec 15. PMID: 36523164
  • Rathnasinghe R, Jangra S, Cupic A, Martínez-Romero C, Mulder LCF, Kehrer T, Yildiz S, Choi A, Mena I, De Vrieze J, Aslam S, Stadlbauer D, Meekins DA, McDowell CD, Balaraman V, Richt JA, De Geest BG, Miorin L, Krammer F, Simon V, García-Sastre A, Schotsaert M. The N501Y mutation in SARS-CoV-2 spike leads to morbidity in obese and aged mice and is neutralized by convalescent and post-vaccination human sera. medRxiv : the preprint server for health sciences. 2021 Jan 20. PMID: 33501468
  • Stadlbauer D, Tan J, Jiang K, Hernandez MM, Fabre S, Amanat F, Teo C, Arunkumar GA, McMahon M, Capuano C, Twyman K, Jhang J, Nowak MD, Simon V, Sordillo EM, van Bakel H, Krammer F. Repeated cross-sectional sero-monitoring of SARS-CoV-2 in New York City. Nature. 2021 Feb;590(7844):146-150. Epub 2020 Nov 3. PMID: 33142304
  • Duty JA, Kraus T, Zhou H, Zhang Y, Shaabani N, Yildiz S, Du N, Singh A, Miorin L, Li D, Stegman K, Ophir S, Cao X, Atanasoff K, Lim R, Mena I, Bouvier NM, Kowdle S, Carreño JM, Rivero-Nava L, Raskin A, Moreno E, Johnson S, Rathnasinghe R, Pai CI, Kehrer T, Cabral EP, Jangra S, Healy L, Singh G, Warang P, Simon V, Sordillo EM, van Bakel H, Liu Y, Sun W, Kerwin L, Teijaro J, Schotsaert M, Krammer F, Bresson D, García-Sastre A, Fu Y, Lee B, Powers C, Moran T, Ji H, Tortorella D, Allen R. Discovery and intranasal administration of a SARS-CoV-2 broadly acting neutralizing antibody with activity against multiple Omicron subvariants. Med (New York, N.Y.). 2022 Oct 14;3(10):705-721.e11. Epub 2022 Aug 8. PMID: 36044897
  • Bohan D, Ert HV, Ruggio N, Rogers KJ, Badreddine M, Aguilar Briseño JA, Rojas Chavez RA, Gao B, Stokowy T, Christakou E, Micklem D, Gausdal G, Haim H, Minna J, Lorens JB, Maury W. Phosphatidylserine Receptors Enhance SARS-CoV-2 Infection: AXL as a Therapeutic Target for COVID-19. bioRxiv : the preprint server for biology. 2021 Jun 24. PMID: 34159331
  • Kehrer T, Cupic A, Ye C, Yildiz S, Bouhhadou M, Crossland NA, Barrall E, Cohen P, Tseng A, Çağatay T, Rathnasinghe R, Flores D, Jangra S, Alam F, Mena N, Aslam S, Saqi A, Marin A, Rutkowska M, Ummadi MR, Pisanelli G, Richardson RB, Veit EC, Fabius JM, Soucheray M, Polacco BJ, Evans MJ, Swaney DL, Gonzalez-Reiche AS, Sordillo EM, van Bakel H, Simon V, Zuliani-Alvarez L, Fontoura BMA, Rosenberg BR, Krogan NJ, Martinez-Sobrido L, García-Sastre A, Miorin L. Impact of SARS-CoV-2 ORF6 and its variant polymorphisms on host responses and viral pathogenesis. bioRxiv : the preprint server for biology. 2022 Nov 30. PMID: 36299428
  • Thorne LG, Bouhaddou M, Reuschl AK, Zuliani-Alvarez L, Polacco B, Pelin A, Batra J, Whelan MVX, Ummadi M, Rojc A, Turner J, Obernier K, Braberg H, Soucheray M, Richards A, Chen KH, Harjai B, Memon D, Hosmillo M, Hiatt J, Jahun A, Goodfellow IG, Fabius JM, Shokat K, Jura N, Verba K, Noursadeghi M, Beltrao P, Swaney DL, Garcia-Sastre A, Jolly C, Towers GJ, Krogan NJ. Evolution of enhanced innate immune evasion by the SARS-CoV-2 B.1.1.7 UK variant. bioRxiv : the preprint server for biology. 2021 Jun 7. PMID: 34127972
  • Thorne LG, Bouhaddou M, Reuschl AK, Zuliani-Alvarez L, Polacco B, Pelin A, Batra J, Whelan MVX, Hosmillo M, Fossati A, Ragazzini R, Jungreis I, Ummadi M, Rojc A, Turner J, Bischof ML, Obernier K, Braberg H, Soucheray M, Richards A, Chen KH, Harjai B, Memon D, Hiatt J, Rosales R, McGovern BL, Jahun A, Fabius JM, White K, Goodfellow IG, Takeuchi Y, Bonfanti P, Shokat K, Jura N, Verba K, Noursadeghi M, Beltrao P, Kellis M, Swaney DL, García-Sastre A, Jolly C, Towers GJ, Krogan NJ. Evolution of enhanced innate immune evasion by SARS-CoV-2. Nature. 2022 Feb;602(7897):487-495. Epub 2021 Dec 23. PMID: 34942634
  • Escalera A, Gonzalez-Reiche AS, Aslam S, Mena I, Laporte M, Pearl RL, Fossati A, Rathnasinghe R, Alshammary H, van de Guchte A, Farrugia K, Qin Y, Bouhaddou M, Kehrer T, Zuliani-Alvarez L, Meekins DA, Balaraman V, McDowell C, Richt JA, Bajic G, Sordillo EM, Dejosez M, Zwaka TP, Krogan NJ, Simon V, Albrecht RA, van Bakel H, García-Sastre A, Aydillo T. Mutations in SARS-CoV-2 variants of concern link to increased spike cleavage and virus transmission. Cell host & microbe. 2022 Mar 9;30(3):373-387.e7. Epub 2022 Jan 21. PMID: 35150638
  • Jangra S, Ye C, Rathnasinghe R, Stadlbauer D, Personalized Virology Initiative study group, Krammer F, Simon V, Martinez-Sobrido L, García-Sastre A, Schotsaert M, Alshammary H, Amoako AA, Awawda MH, Beach KF, Bermúdez-González MC, Chernet RL, Eaker LQ, Ferreri ED, Floda DL, Gleason CR, Kleiner G, Jurczyszak D, Matthews JC, Mendez WA, Mulder LCF, Russo KT, Salimbangon AT, Saksena M, Shin AS, Sominsky LA, Srivastava K. SARS-CoV-2 spike E484K mutation reduces antibody neutralisation. The Lancet. Microbe. 2021 Jul;2(7):e283-e284. Epub 2021 Apr 7. PMID: 33846703
  • Aydillo T, Rombauts A, Stadlbauer D, Aslam S, Abelenda-Alonso G, Escalera A, Amanat F, Jiang K, Krammer F, Carratala J, García-Sastre A. Immunological imprinting of the antibody response in COVID-19 patients. Nature communications. 2021 Jun 18;12(1):3781. PMID: 34145263
  • Mack PC, Hirsch FR, Bunn PA, Minna JD. Longitudinal Analyses of COVID-19 Vaccination in Patients With Lung Cancer: Antibody Responses and Variant-Specific Neutralization. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2022 Nov 20;40(33):3787-3789. Epub 2022 Jun 27. PMID: 35759731
  • Gao S, Esparza M, Dehghan I, Aksenova V, Zhang K, Batten K, Ferretti MB, Begg BE, Cagatay T, Shay JW, García-Sastre A, Goldsmith EJ, Chen ZJ, Dasso M, Lynch KW, Cobb MH, Fontoura BMA. Nuclear speckle integrity and function require TAO2 kinase. Proceedings of the National Academy of Sciences of the United States of America. 2022 Jun 21;119(25):e2206046119. Epub 2022 Jun 15. PMID: 35704758
  • Sindelar M, Stancliffe E, Schwaiger-Haber M, Anbukumar DS, Albrecht RA, Liu WC, Travis KA, García-Sastre A, Shriver LP, Patti GJ. Longitudinal Metabolomics of Human Plasma Reveals Robust Prognostic Markers of COVID-19 Disease Severity. medRxiv : the preprint server for health sciences. 2021 Feb 8. PMID: 33564793
  • Jangra S, Ye C, Rathnasinghe R, Stadlbauer D, Krammer F, Simon V, Martinez-Sobrido L, Garcia-Sastre A, Schotsaert M. The E484K mutation in the SARS-CoV-2 spike protein reduces but does not abolish neutralizing activity of human convalescent and post-vaccination sera. medRxiv : the preprint server for health sciences. 2021 Jan 29. PMID: 33532796
  • Reuschl AK, Thorne LG, Zuliani-Alvarez L, Bouhaddou M, Obernier K, Hiatt J, Soucheray M, Turner J, Fabius JM, Nguyen GT, Swaney DL, Rosales R, White KM, Avilés P, Kirby IT, Melnyk JE, Shi Y, Zhang Z, Shokat KM, García-Sastre A, Jolly C, Towers GJ, Krogan NJ. Host-directed therapies against early-lineage SARS-CoV-2 retain efficacy against B.1.1.7 variant. bioRxiv : the preprint server for biology. 2021 Feb 4. PMID: 33501437
  • Cohen P, DeGrace EJ, Danziger O, Patel RS, Barrall EA, Bobrowski T, Kehrer T, Cupic A, Miorin L, García-Sastre A, Rosenberg BR. Unambiguous detection of SARS-CoV-2 subgenomic mRNAs with single cell RNA sequencing. bioRxiv : the preprint server for biology. 2023 Feb 23. PMID: 34845443
  • Krammer F, Schultz-Cherry S. We need to keep an eye on avian influenza. Nature reviews. Immunology. 2023 May;23(5):267-268. PMID: 36944755