Daniel  McGrail,  PhD

Daniel McGrail, PhD

Assistant Staff

Lerner Research Institute, 9500 Euclid Avenue, Cleveland, Ohio 44195


Research in the McGrail lab integrates systems-level analyses with controlled experimental models in order to advance precision medicine in oncology and other human diseases. We use an array of large-scale data (e.g. genetic variation, epigenetic modifications, transcriptomics, proteomics, highly multiplexed imaging, and functional genomics) to inform our in vitro and in vivo systems.

We are particularly interested in applying this toolkit to better understand determinants of immune checkpoint blockade (ICB) sensitivity. We found that correlates of tumor immunogenicity and ICB response may be largely divergent between different types of cancers (Annals of Oncology 2021, Science Translational Medicine 2021, Nature Communications 2018). We hypothesize these dichotomous associations may indicate underlying fundamental differences in drivers of ICB sensitivity and resistance. By understanding these difference we hope to improve patient stratification for treatment with ICB and identify novel approaches to enhance anti-tumor immunity. Additional areas of interest include DNA damage response (Cancer Cell 2019, Cancer Cell 2020, npj Sys Bio and Appl 2017), functional genomics, and biomarker discovery.

Now Hiring

The McGrail lab is actively seeking applicants for research scientist, graduate student, and postdoctoral fellow positions. Experience with molecular biology techniques, immunohistochemistry, and/or preclinical research is advantageous but not required. Applicants should send a cover letter summarizing research experience and future goals, their CV, and contact information for 3-5 references to Dr. Daniel McGrail at mcgraid@ccf.org.

View all publications on Google Scholar.

Selected Publications:

McGrail DJ, Pilié PG, Rashid NU, Voorwerk L, Slagter M, Kok M, Jonasch E, Khasraw M, Heimberger AB, Ueno NT, Ferrarotto R, Chang JT, Lin SY. Validation of cancer-type-dependent benefit from immune checkpoint blockade in TMB-H tumors identified by the FoundationOne CDx assay. Ann Oncol. 2022 Aug 1:S0923-7534(22)01860-9. doi: 10.1016/j.annonc.2022.07.009. 

McGrail DJ*#, Garnett J#, Yin J, Shih D, Li Y, Sun C, Li Y, Schmandt R, Wu JY, Hu L, Liang Y, Peng G, Menter D, Yates MS, Kopetz S, Lu K, Broaddus R, Mills GB, Sahni N*, Lin SY*. Proteome instability is a therapeutic vulnerability in mismatch repair deficient cancer. Cancer Cell (2020)37:371-386 

McGrail DJ*, Pilié PG, Dai H, Truong NAL, Liang Y, Zhang XHF, Rosen JM, Heimberger AB, Peterson CB, Jonasch E, Lin SY*. Replication stress response defects predict response to immune checkpoint blockade. Science Translational Medicine (2021)12:eabe6201 

McGrail DJ*, Pilié PG, Rashid NU, Voorwerk L, Slagter M, Kok M, Jonasch E, Khasraw M, Heimberger AB, Lim B, Ueno NT, Litton JK, Ferrarotto R, Chang JT, Moulder SL, Lin SY*. High tumor mutation burden fails to universally predict immune checkpoint blockade response. Annals of Oncology (2021)32:661-672 

McGrail DJ, Federico L, Li Y, Dai H, Lu Y, Mills GB, Yi S, Lin SY, Sahni N. Multiomics analysis reveals neoantigen-independent immune cell infiltration in copy-number driven cancers. Nature Communications (2018)9:1317 

Fang Y, McGrail DJ, Sun C, Labrie M, Chen X, Zhang D, Ju Z, Vellano CP, Lu Y, Li Y, Jeong KJ, Ding Z, Liang J, Wang SW, Dai H, Lee S, Sahni N, Kim T, Chen K, Mercado-Uribe I, Lin SY, Peng G, Westin SN, Liu J, O’Connor MJ, Yap TA, Mills GB. Sequential therapy with PARP and WEE1 inhibitors minimizes toxicity while maintaining efficacy. Cancer Cell (2019)35:851-867. 

Federico L#, McGrail DJ#, Bentebibel SE, Haymaker C, Ravelli A, Forget MA, Karpinets T, Reuben A, Mitchell KG, Bayley EC, Celestino M, Weissferdt A, Vaporciyan A, Antonoff M, Walsh G, Lin SY, Futreal A, Wistuba I, Roth J, Roarty E, Lacerda L, Swisher S, Cascone T, Zhang J, Heymach JV, Sepesi B, Gibbons DL, Bernatchez C. Distinct tumor-infiltrating lymphocyte landscapes are associated with clinical outcomes in non-small cell lung cancer. Annals of Oncology (2021)33:42-56 

Shah P, Forget MA, Frank ML, Federico L, Jiang P, Khairullah r, Wistuba II, Chow CW, Long Y, Fujimoto J, Lin SY, Maitra A, Negrao MV, Mitchell KG, Weissferdt A, Vaporciyan AA, Cascone T, Roth J, Zhang J, Sepesi B, Gibbons DL, Heymach JV, Haymaker C, McGrail DJ*, Reuben A*, Bernatchez C*. Combined IL-2, agonistic CD3 and 4-1BB stimulation preserve clonotype hierarchy in propagated non-small cell lung cancer tumor-infiltrating lymphocytes. Journal for the ImmunoTherapy of Cancer (2022) 10:e003082.

Liu X, Kong W,  Peterson CB, McGrail DJ, Hoang A, Zhang X, Lam T, Pilié PG, Zhu H, Beckermann KE, Haake SM, Isgandrova S, Martinez-Moczygemba M, Sahni N, Lin SY, Rathmell WK, Jonasch E. PBRM1 loss defines distinct tumor phenotype associated with immunotherapy resistance in renal cell carcinoma. Nature Communications(2020)11: 2135 

McGrail DJ*, Dai J, McAndrews KM, Kalluri R*. Enacting national social distancing policies corresponds with dramatic reduction in COVID19 infection rates, PLoS One 15, e0236619 (2020). 

#authors contributed equally, *co-corresponding authors

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