James Robinson - The Hormel Institute

James Robinson Ph.D
Assistant Professor
robinsoj@umn.edu

Cell Signaling & Tumorigenesis

Biography

I developed my vocation for cancer research after my grandmother passed away from Colon Cancer. After completing my bachelor’s and master’s degrees I began my career as a scientific officer responsible for the management of the Cancer Research UK colorectal tissue bank at St Marks Hospital in London, England. Before beginning a PhD program in gastrointestinal tumorigenesis under the tutelage of Professors Andrew Silver and Ian Tomlinson. After the completion of my PhD program, I moved to Professor Sheri Holmen’s Laboratory in the USA. Together we developed several novel models to study the formation of and drug resistance in glioma and melanoma. In 2013 I applied for and was awarded the prestigious NIH NCI R99/R00 pathway to independent award and established my lab at the Hormel institute in Minnesota in November of 2014. In 2017, I received the American Cancer Society (ACS) Research Scholar Award to expand my research into drug resistance in melanoma. This award is given to a very limited number of promising scientists each year, and past receipts include some of the nation’s leading scientists. My long-term goal is to develop tailored molecular therapeutics for melanoma and glioma.

Education

B.Sc
06/2001 – Biotechnology
University of Westminster, London, England
M.Sc.
06/2002 – Genetics & Immunology
Brunel University, Uxbridge, England
Ph.D.
03/2009 – Tumor Biology
Queen Marys, University of London, England
Post-doc
11/2014 – Cancer Research
Huntsman Cancer Institute, Utah

Professional memberships

2008
Member, American Association for Cancer Research
2015
Member, The Society for Melanoma Research
2016
Member, Institutional Biosafety Committee, University of Minnesota
2015
Member, Masonic Cancer Center, Minneapolis, MN

Publications

1. H. Yang, D. A Kircher. K. H, Kim, A. H Grossmann, M. W VanBrocklin, S. L Holmen, J. P Robinson. Activated MEK cooperates with Cdkn2a and Pten loss to promote the development and maintenance of melanoma. Oncogene. 2017 Jul 6;36(27):3842-3851.

2. J. P Robinson, V.W Rebecca, D. A Kircher, M. R Silvis, I Smalley, G. T Gibney, K. J Lastwika, G. Chen, M. A Davies, D. Grossman, K. S Smalley, S. L Holmen, M. W VanBrocklin. Resistance mechanisms to genetic suppression of mutant NRAS in melanoma. Melanoma Res. 2017 Dec;27(6):545-557.

3. C. H Shin, J. P Robinson, J Sonnen, A. Welker, D Yu, M.W VanBrocklin, S. L Holmen. HBEGF models the classical subtype of glioblastoma in the context of Ink4a/Arf and Pten loss. Oncogene. 2017 Aug 10;36(32):4610-4618.

4. G. L Robinson, B Philip, M Guthrie, J Cox, J. P Robinson, M. W VanBrocklin, S.L Holmen. In vitro visualization and characterization of wild type and mutant IDH homo- and heterodimers using Bimolecular Fluorescence Complementation. Cancer Research Frontiers. 2016 May;2 (2) 311-329.

5. J. H Cho, J. P Robinson*, R. A Arave, W. J Burnett, D. A Kircher, G Chen, M. A Davies, A. H Grossmann, M.W VanBrocklin, M. McMahon, S.L Holmen. AKT1 Activation Promotes Development of Melanoma Metastases. Cell Reports. 2015 Nov 3;13(5):898-905. (*= Joint first author)

6. C. H Shin, A.H Grossmann, S. L Holmen, J. P Robinson. The BRAF kinase domain promotes the development of gliomas in vivo. Genes & Cancer. 2015 (1-2):9-18.

7. G. L. Robinson, J. P Robinson, K. J Lastwika, S.L Holmen and M. W. VanBrocklin. Akt signaling accelerates tumor recurrence following Ras inhibition in the context of Ink4a/Arf loss. 2013 Genes & Cancer, 476-85.

8. M. W. VanBrocklin, J. P Robinson and S. L Holmen. Ink4a/Arf loss promotes tumor recurrence following Ras inhibition. Neuro-Oncology. 2012 14(1):34-42.

9. J. P Robinson, M. W. VanBrocklin, K. J Lastwika, A.J. McKinney, S. Brandner and S.L. Holmen. Activated MEK cooperates with Ink4a/Arf loss or Akt activation to induce gliomas in vivo. Oncogene. 2011 30, 1341-

10. J. P Robinson, M. W. VanBrocklin, A. J McKinney, H.G Gach, and S.L. Holmen. (Akt signaling is required for glioblastoma maintenance in vivo. American Journal of Cancer Research. 2011 1(2):155-167

11. C. Lai*, J. P Robinson*, S. Clark, G. Stamp, R. Poulsom and A. Silver. Expression Array Profiling Identifies Elevation of WNT5A Expression in Polyp Formation in Lkb1+/- Mice and Peutz-Jeghers Syndrome. The Journal of Pathology. 2011 223(5):584-92. (*= Joint first authors)

12. M. W VanBrocklin*, J. P Robinson*, K. Lastwika, A. R. Guilbeault, J. D. Khoury, and S. L. Holmen. Somatic cell gene delivery of NRASQ61R to melanocytes in vivo induces melanoma in the context of Ink4a/Arf deficiency. Pigment Cell Melanoma Res. 2010 Aug;23(4):531-41. (*= Joint first authors)

13. J. P. Robinson, M.W VanBrocklin, A.R. Guilbeault, S. Brandner and S.L. Holmen. Activated BRAF induces gliomas in mice when combined with Ink4a/Arf loss or Akt activation. Oncogene, 2010 29, 335–344.

14. M. W. VanBrocklin, J. P. Robinson, T. Whitwam, A.R. Guilbeault, J. Koeman, P.J. Swiatek, G.F. Vande Woude, J.D. Khoury, and S.L. Holmen. Met amplification and tumor progression in Cdkn2a-deficient melanocytes. Pigment Cell and Melanoma Research. 20019 22, 454 – 460.

15. J. P Robinson, A. Martin, E. Nye, I. Tomlinson, A. Silver. Oral rapamycin reduces tumour burden and vascularization in Lkb1+/- mice. The Journal of Pathology. 2009 219, 35-40.

16. J. P Robinson, E. Nye, G. Stamp, and S. Silver. Osteogenic tumours in Lkb1-deficient mice. Exp Mol Pathol, 2008 85, 223-226.

17. O. C Will, J. P Robinson, T Gunther, R. K Phillips, S. K Clark, and I. Tomlinson. APC mutation spectrum in ileoanal pouch polyps resembles that of colorectal polyps. 2008 Br J Surg 95, 765-9.

18. P. Alhopuro, D. Phichith, S. Tuupanen, H. Sammalkorpi, M. Nybondas, J. Saharinen, J.P. Robinson, Z. Yang, L.Q. Chen, T. Orntoft, J.P. Mecklin, H. Jarvinen, C. Eng, G. Moeslein, D. Shibata, R.S. Houlston, A. Lucassen, I.P. Tomlinson, V. Launonen, A. Ristimaki, D. Arango, A. Karhu, H.L. Sweeney, and L.A. Aaltonen. Unregulated smooth-muscle myosin in human intestinal neoplasia. Proc Natl Acad Sci U S A, 2008 105, 5513-8.

19. E. Volikos,* J. P Robinson*, K Aittomaki, J.P Mecklin, H. Jarvinen, A. M Westerman, F. W de Rooji, T. Vogel, G. Moeslein, V. Launonen, I. P Tomlinson,. A. R Silver, and L. A Aaltonen. LKB1 exonic and whole gene deletions are a common cause of Peutz-Jeghers syndrome J Med Genet, 2006 43(5), e18. (*= Joint first authors)

20. N. Suraweera, J. P. Robinson*, E. Volikos, T. Guenther, I. Talbot, I. Tomlinson, and A. Silver. Mutations within Wnt pathway genes in sporadic colorectal cancers and cell lines Int J Cancer. 2006 119(8), 1837- 1842.

21. O.M Sieber, S. Segditsas, A. L Knudsen, J. Zhang, J. Luz, A. J Rowan, S. L Spain, C. Thirlwell, K. M Howarth,E. E Jaeger, J. P. Robinson, E. Volikos, E., Silver, A., Kelly, G., Aretz, S., Frayling, I., Hutter, P., Dunlop, M.,Guenther, T., Neale, K., Phillips, R., Heinimann, K., and Tomlinson, I. P. Disease severity and genetic pathways in attenuated familial adenomatous polyposis vary greatly but depend on the site of the germline mutation. Gut, 2006 55(10), 1440-1448.

22. J. P. Robinson, V.L Johnson, P. A Rogers, R. S Houlston, E. R, Maher, D. T Bishop, D. G Evans, H. J Thomas, I. P Tomlinson, and A. R Silver. Evidence for an association between compound heterozygosity for germ line mutations in the hemochromatosis (HFE) gene and increased risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev, 2005 14(6), 1460-1463.

23. H. Rasinpera, C. Forsblom, N. S Enattah, P. Halonen, K.H Salo, S. Enholm, G. Sellick, H. Alazzouzi, H., R. Houlston, J. P. Robinson, P.H Groop, I. Tomlinson, S. Schwartz, L .A Aaltonen, and I. Jarvela. The C/C-13910 genotype of adult-type hypolactasia is associated with an increased risk of colorectal cancer in the Finnish population. Gut, 2005 54(5), 643-647.

Contact Information

Primary Research Areas

My research focuses on the use of pre-clinical models to define the genes required for tumor initiation, maintenance, and progression with the ultimate goal of identifying novel targets for therapeutic intervention.
Melanoma: We have developed a novel retroviral gene delivery mouse model of melanoma that permits control of oncogene expression using tetracycline. This mouse model faithfully recapitulates the etiology, histopathology, and biology of melanoma and provides an exceptional experimental system to discover novel therapeutic targets. Using this model we have determined Pten loss or AKT activation increases the frequency of brain and lung metastasis. We also used this system to determine the efficacy of targeting NRAS and BRAF as a therapy for malignant melanoma ‘Receptor tyrosine kinase signaling mediates resistance in NRAS mutant melanoma’. We have recently demonstrate that many of the MEK mutations found in resistant melanomas are unlikely to drive resistance to BRAF inhibition alone, and none studied had a significant capacity to drive resistance to combined BRAF and MEK inhibition alone. We are in the process of defining and validating mechanisms of resistance to BRAF and MEK inhibition and testing coordinated strategy of pre-emptive, targeted therapies for melanoma to prevent recurrence.

Glioma: Glioblastoma multiforme (GBM) is by far the most frequent and deadly primary brain tumor in adults, with 5-year survival rates for adults below 10%. Paediatric GBM confers the worst prognosis of any paediatric cancer with a 5-year survival rate of <1%. Mutations in Histone H3.3 variant H3F3A2 (K27M, G34R/V) occur in ~50% of paediatric GBMs and mutations in isocitrate dehydrogenase 1 or 2 (IDH1 R132H,S,C,G,L & IDH2 R172H,K) occur in ~80% of adult low grade gliomas and ~98% of secondary GBMs, which progressed from lower grade tumors. Histone H3.3 and IDH1 mutations are mutually exclusive and have been established as an early events in pathogenesis. We are currently using our extensive animal modeling experience to study how H3.3 and IDH mutation drive tumorigenesis.

Research Specialties

Cell signaling, Tumor pathology, Mouse Modeling

Awards

2004
Cancer Research UK stipend award, Cancer Research UK
2009
Life Member of Queen Mary’s College London, University of London
2009
Invited speaker, RCAS mouse modeling conference, Nevada Cancer Institute
2010
Scholar in Training, American Association for Cancer Research
2018
American Cancer Society Research Scholar