Cures Start Here. At Fred Hutchinson Cancer Research Center, home to three Nobel laureates, interdisciplinary teams of world-renowned scientists seek new and innovative ways to prevent, diagnose and treat cancer, HIV/AIDS and other life-threatening diseases. Fred Hutch’s pioneering work in bone marrow transplantation led to the development of immunotherapy, which harnesses the power of the immune system to treat cancer. An independent, nonprofit research institute based in Seattle, Fred Hutch houses the nation’s first cancer prevention research program, as well as the clinical coordinating center of the Women’s Health Initiative and the international headquarters of the HIV Vaccine Trials Network. Careers Start Here.
Postdoctoral Research Fellows in immuno-oncology – Novel cancer immunotherapies
Immunotherapies, such as checkpoint inhibition and adoptive T cell therapies, represent a paradigm shift in the treatment of cancer, inducing impressive responses in diverse malignancies. However, not all patients respond to current immunotherapies and novel therapeutic approaches are needed to circumvent these obstacles.
Post-Doctoral Research Fellow positions are available in the Immunotherapy Integrated Research Center at the Fred Hutchinson Cancer Research Center. The successful applicants will join a collaborative team that combines clinical research, animal modeling, computational biology and multiplexed immuno-histochemistry to understand the basic mechanisms of antitumor immunity and apply them to the development of novel immunotherapies.
This research program includes the laboratories of: Dr. Aude Chapuis, a translational immuno-oncologist who specializes in adoptive T cell therapies; Dr. Anthony Rongvaux, an immunologist who develops innovative humanized murine models to study the tumor/immune interface; Dr. Raphael Gottardo, a biostatistician with expertise in high-dimensional single cell data analysis; and Dr. Robert Pierce, a pathologist and expert in tumor microenvironment analyses who previously developed tissue-based biomarkers for Merck’s anti-PD-1 pembrolizumab antibody.
Our research is focused on understanding the biology and improving clinical outcomes after immune-boosting treatments. Human adoptive immunotherapy trials are initiated and being conducted using the robust Fred Hutch clinical platform. We are performing detailed analysis of patient outcomes to inform next-generation trials, and developing humanized murine models of checkpoint inhibition and adoptive T cell therapy against solid and liquid cancers. We are using single cell RNA sequencing, genome editing and genomic screens in humanized murine to understand how anti-tumoral immunity functions, why it fails in some patients, and how we can overcome current limitations. We use multiparametric immunohistochemistry to validate humanized mouse results in humans, using a large biorepository of annotated patient specimens.
The scientific questions being addressed include:
The overall objective of this interdisciplinary project is to provide the scientific basis for future clinical trials, leveraging Fred Hutch’s continuing leadership in the design, clinical testing and commercialization of successful anticancer drugs and immunotherapies.
Desired skills and experience of the applicants:
The successful candidates will be scientifically driven individuals who enjoy working in a highly collaborative environment, with a track record of productive research, demonstrated by at least one first author publication, and with excellent communication skills.
Please apply online with a letter summarizing previous work experience, personal strengths and future interests, a resume, and contact information for three professional references.
Paulson KG, Voillet V, McAfee MS, Hunter DS, Wagener FD, Perdicchio M, Valente WJ, Koelle SJ, Church CD, Vandeven N, Thomas H, Colunga AG, Iyer JG, Yee C, Kulikauskas R, Koelle DM, Pierce RH, Bielas JH, Greenberg PD, Bhatia S, Gottardo R, Nghiem P, Chapuis AG.
Acquired cancer resistance to combination immunotherapy from transcriptional loss of class I HLA.
Nat Commun. 2018 Sep 24;9(1):3868. PMID: 30250229.
Chapuis AG, Desmarais C, Emerson R, Schmitt TM, Shibuya K, Lai I, Wagener F, Chou J, Roberts IM, Coffey DG, Warren E, Robbins H, Greenberg PD, Yee C.
Tracking the Fate and Origin of Clinically Relevant Adoptively Transferred CD8(+) T Cells In Vivo.
Sci Immunol. 2017 Feb;2(8). PMID: 28367538.
Chapuis AG, Lee SM, Thompson JA, Roberts IM, Margolin KA, Bhatia S, Sloan HL, Lai I, Wagener F, Shibuya K, Cao J, Wolchok JD, Greenberg PD, Yee C.
Combined IL-21-primed polyclonal CTL plus CTLA4 blockade controls refractory metastatic melanoma in a patient.
J Exp Med. 2016 Jun 27;213(7):1133-9. PMID: 27242164.
Rongvaux A, Willinger T, Martinek J, Strowig T, Gearty SV, Teichmann LL, Saito Y, Marches F, Halene S, Palucka AK, Manz MG, Flavell RA.
Development and function of human innate immune cells in a humanized mouse model.
Nat Biotechnol. 2014 Apr;32(4):364-72. PMID: 24633240.
Rongvaux A, Takizawa H, Strowig T, Willinger T, Eynon EE, Flavell RA, Manz MG.
Human hemato-lymphoid system mice: current use and future potential for medicine.
Annu Rev Immunol. 2013;31:635-674. PMID: 23330956.
McDavid A, Finak G, Gottardo R.
The contribution of cell cycle to heterogeneity in single-cell RNA-seq data.
Nat Biotechnol. 2016 Jun 9;34(6):591-3. PMID: 27281413.
Finak G, McDavid A, Yajima M, Deng J, Gersuk V, Shalek AK, Slichter CK, Miller HW, McElrath MJ, Prlic M, Linsley PS, Gottardo R.
MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data.
Genome Biol. 2015 Dec 10;16:278. PMID: 26653891.
Stromnes IM, Hulbert A, Pierce RH, Greenberg PD, Hingorani SR.
T-cell Localization, Activation, and Clonal Expansion in Human Pancreatic Ductal Adenocarcinoma.
Cancer Immunol Res. 2017 Nov;5(11):978-991. PMID: 29066497.
Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, West AN, Carmona M, Kivork C, Seja E, Cherry G, Gutierrez AJ, Grogan TR, Mateus C, Tomasic G, Glaspy JA, Emerson RO, Robins H, Pierce RH, Elashoff DA, Robert C, Ribas A.
PD-1 blockade induces responses by inhibiting adaptive immune resistance.
Nature. 2014 Nov 27;515(7528):568-71. PMID: 25428505.