Kathleen C.F. Sheehan, PhD

Division

• Immunobiology

Additional Titles

• Director, Hybridoma Center
• Center for Human Immunology and Immunotherapy Programs, Co-Head, Immunomonitoring Laboratory, Director of Immunoassays

Additional Professional Links

• Hybridoma Center
• CHiiPs

Education

• BS: University of Notre Dame, South Bend, IN (1980)
• PhD: St. Louis University School of Medicine, St. Louis, MO (1986)

Honor Soceity Memberships

• Alpha Sigma Nu

Research Interests

Sheehan has a long-standing interest in the role of cytokines, particularly the interferons and tumor necrosis factor, in immune and infectious diseases and cancer immunotherapy. Current work is focused on understanding the mechanism(s) of action of new models of immune checkpoint therapy (ICT), as well as combinatorial treatment strategies using defined syngeneic murine sarcoma models. Antibodies developed in our laboratory that bind TNFR2 have been particularly effective to induce tumor rejection in murine models. Use of high-dimensional analyses provides a strategy to monitor changes within distinct cellular populations in response to ICT and identify synergistic mechanisms and new targets.

In addition to her research studies, Dr. Sheehan also directs two shared resource facilities. The Hybridoma Center (HC) within the Department of Pathology and Immunology provides comprehensive monoclonal antibody (mAb) development services for investigators within our research community as well as the broader scientific community. In particular, Sheehan has exploited the Armenian hamster model to develop functional mAb to variety of murine or human targets as well as pathogens. The facility is widely recognized for its expertise in genetic immunization techniques and development of novel reagents, producing mAb of both research and clinical / immunodiagnostic significance. https://pathology.wustl.edu/research/core-facilities/hybridoma-center/

Sheehan also serves as Co-Head of the Immunomonitoring Laboratory (IML) within the Bursky Center for Human Immunology and Immunotherapy Programs (CHiiPs). The IML was established to provide the structure, state-of-the-art instrumentation and expertise to monitor the impact of specific immunotherapies on human and mouse immunologic profiles, interrogate mechanisms and pathways related to the treatment protocols and advance the conceptual basis for targeted treatment strategies. Director of the Immunoassay Group. She was instrumental in the physical set-up, staffing and implementation of Core services, serves as the Director of the Immunoassays Group and continues to drive the development and expansion of activities of this shared resource. www.chiips.wustl.edu

Selected Publications

Sheehan KCF, Lai KS, Dunn GP, Bruce AT, Diamond MS, Heutel JD, Dungo-Arthur C, Carrero JA, White JM, Hertzog PJ and Schreiber RD. Blocking Monoclonal Antibodies Specific for Mouse IFNalpha/beta Receptor Subunit 1 (IFNAR1) from Mice Immunized by In Vivo Hydrodynamic Transfection. J Interferon Cytokine Res. 2006:26:804-819. PMID: 17115899

Uppaluri R, Sheehan KCF, Wang L, Bui JD, Brotman JJ, Lu B, Gerard C, Hancock WW and Schreiber RD.  Prolongation of cardia and islet allograft survival by a blocking hamster anti-mouse CXCR3 monoclonal antibody. Transplantation 2008:86:137-47. PMC3140461.

Chan SR, Rickert CG, Vermi W, Sheehan KC, Arthur C, Allen JA, White JM, Archambault J, Lonardi S, McDevitt TM, Bhattacharya D, Lorenzi MV, Allred DC, Schreiber RD. Dysregulated STAT1-SOCS1 control of JAK2 promotes mammary luminal progenitor cell survival and drives ERα(+) tumorigenesis. Cell Death Differ. 2014:21(2):234-46. PMC3890946

Sheehan KCF, Lazear HM, Diamond MS, Schreiber RD. Selective blockade of interferon-a and –b reveals their non-redundant functions in a mouse model of West Nile virus infection. PLoS One. 2015. May 26;10(5):e0128636. doi: 10.1371/journal.pone.0128636. PMC4444312

Gubin MM, Esaulova E, Ward JP, Malkova ON, Runci D, Wong P, Noguchi T, Arthur CD, Meng W, Alspach E, Medrano RFV, Fronick C, Fehlings M, Newell EW, Fulton RS, Sheehan KCF, Oh ST, Schreiber RD and Artyomov MN. High -dimensional analysis delineates myeloid and lymphoid compartment remodeling during successful immune-checkpoint cancer therapy.  2018. Cell 175:1-17. PMC6501221

Alspach E, Lussier DM, Miceli AP, Kizhvatov I, DuPage M, Luoma AM, Meng W, Lichti CF, Esaulova E, Vomund AN, Runci D, Ward JP, Gubin MM, Medrano RFV, Arthur CD, White JM, Sheehan KCF, Chen A, Wucherpfennig KW, Jacks T, Unanue ER, Artyomov MN and Schreiber RD. MHC-II neoantigens shape tumor immunity and response to immune checkpoint therapy. 2019. Nature. Oct;574(7780):696-701. doi: 10.1038/s41586-019-1671-8. Epub 2019 Oct 23. PMC6858572

Cook LE, Locke MC, Young AR, Monte K, Hedberg ML, Shimak RM, Sheehan KCF, Veis DJ, Diamond MS, and Lenschow DJ.  Distinct roles of interferon alpha and beta in controlling chikungunya virus replication and modulating neutrophil-mediated inflammation. 2019. J Virol. 2019 Dec 12;94(1):e00841-19. doi: 10.1128/JVI.00841-19. Print 2019 Dec 12. PMC6912113

Wells DK, van Buuren MM, Dang KK, Hubbard-Lucey VM, Sheehan KCF, Campbell KM, Lamb A, Ward JP, Sidney J, Blazquez AB, Rech AJ, Zaretsky JM, Comin-Anduix B, Ng AHC, Chour W, Yu TV, Rizv Hi, Chen JM, Manning P, Steiner GM, Doan XC, The TESLA Consortium, Merghoub T, Guinney J, Kolom A, Selinsky C, Ribas A, Hellmann MD, Hacohen N, Sette A, Heath JR, Bhardwaj N, Ramsdell F, Schreiber RD, Schumacher TN, Kvistborg P, Defranoux NA. Key Parameters of Tumor Epitope Immunogenicity Revealed Through a Consortium Approach Improve Neoantigen Prediction.  Cell. 2020; Oct 29;183(3):818-834.e13.  doi: 10.1016/j.cell.2020.09.015. PMC7652061.

Bender D, Schaettler M, Sheehan KCF, Johanns T, Dunn GP. 2021. Cytokine profiling in plasma from patients with brain tumors versus healthy individuals using two different multiplex immunoassay platforms. Biomaker Insights. DOI: 10.1177/11772719211006666/ ID: BMI-2020-0076.RV1. PMID: 33854293

Pei J, Beri NR, Zou AJ, Hubel P, Dorando HK, Bergant V, Andrews RD,Pan J, Andres JM,  Sheehan KCF, Pichlmair A, Amarasinghe GK, Brody SL,  Payton JE, and Leung DW  Nuclear-localized human respiratory syncytial virus NS1 protein modulates host gene transcription. Cell Rep.2021, 37(2):109803. doi: 10.1016/j.celrep.2021.109803.

Sultan H, Takeuchi Y, Ward JP, Sharma N, Liu TT, Sukhov V, Firulyova M, Song Y, Ameh S, Brioschi S, Khantakova D, Arthur CD, White JM, Kohlmiller H, Salazar AM, Burns R, Costa H, Moynihan KD, Yeung YA, Djuretic I, Schumacher TN, Sheehan KCF, Colonna M, Allison P, Murphy KM, Artyomov MN and Schreiber RD. 2024. Neoantigen-specific Tr1-like CD4+ T cells suppress cancer immunotherapy. Nature. 024 Aug;632(8023):182-191. doi: 10.1038/s41586-024-07752-y. Epub 2024 Jul 24.PMID: 39048822

Carlson RJ, Patten JJ, Stefanakis G, Soong BY, Radhakrishnan A, Singh A, Thakur N, Sheehan KCF, Amerasinghe GK, Hacohen N, Basler CF, Leung DW, Uhler C, Davey RA and Blainey PC. 2024. Single-cell image-based genetic screens systematically identify regulators of Ebola virus subcellular infection dynamics. Nature Microbiology. In Press.