Research
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.
Biography
Dr. Daniel McGrail completed his undergraduate and graduate studies in Chemical & Biomolecular Engineering at Georgia Institute of Technology, where he studied the role of cell biomechanics in cancer and tissue regeneration. Dr. McGrail completed his postdoctoral training in the Department of Systems Biology at MD Anderson Cancer Center, focusing on integration of computational and experimental approaches to study cancer biology. Dr. McGrail joined the Center for Immunotherapy and Precision Immuno-oncology in February 2022, where he continues his efforts to identify novel targeted therapeutic approaches for patients with cancer, with a particular emphasis DNA damage response and immuno-oncology.
Education & Professional Highlights
Appointed
2022
Education and Fellowships
Postdoctoral Fellowship - University of Texas, MD Anderson Cancer Center
Department of Systems Biology
Houston, TX USA
2022
Graduate - Georgia Institute of Technology
Chemical and Biomolecular Engineering
Atlanta, GA USA
2015
Undergraduate - Georgia Institute of Technology
Chemical and Biomolecular Engineering
Atlanta, GA USA
2012
Awards & Honors
- Thomas H. and Mayme P. Scott Fellowship in Cancer Research
- National Science Foundation Stem Cell Biomanufacturing IGERT Fellow, Georgia Institute of Technology
- National Science Foundation Honorable Mention, Georgia Institute of Technology
- Petit Undergraduate Research Scholar, Georgia Institute of Technology
- Outstanding Undergraduate Research Award, College of Engineering, Georgia Institute of Technology
- President's Undergraduate Research Award, Georgia Institute of Technology
Memberships
- Society for the Immunotherapy of Cancer
2019-present
Research
Overview
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.
In the News
Combined therapy may improve clinical responses for endometrial, colorectal, and gastric tumors | MD Anderson Cancer Center
Protein Instability is Targetable in Mismatch Repair-Deficient Tumors | Cancer Discovery News
Tumor mutational burden does not predict response to immunotherapy in all cancer types | Healio News
High Tumor Mutational Burden Predicts Immunotherapy Response in Some - but Not All - Cancers | American Society of Clinical Oncology Post
High Tumour Mutation Burden Fails to Predict Response to Immune Checkpoint Inhibitors Across All Cancer Types | European Society for Medical Oncology
High-TMB predicts immunotherapy response in bladder but not prostate cancer | Urology Times
Oncologists Look to FDA as New Publications Poke Holes in TMB-High Keytruda Approval | Precision Oncology News
High TMB Fails to Show Predictive Biomarker Potential for Checkpoint Inhibition Across Cancers | OncLive
Researchers Strive to Refine Tumor Mutation Burden | Cancer Discovery News
How targeting a genetic signature of cellular stress may boost cancer immunotherapy | Fierce Biotech
Our Team
Selected Publications
View all publications on Google Scholar.
Selected Publications:
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
Patents
| US Patent | Patent Title | Issue Date | First-Named Inventor |
|---|---|---|---|
| 20210130906 | Replication stress response biomarkers for immunotherapy response | 05/06/2021 | Daniel McGrail |
| 20200017918 | Gene signatures to predict drug response in cancer | 09/20/2022 | Shiaw-Yih Lin |
Careers
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 [email protected].