Page 51 - Hormel Institute Annual Report 2021-22
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 to bring about a better understanding of the role of this mutation in these tumors in order to develop new therapies to improve survival for children with this devastating disease. Melanoma is the most dangerous form of skin cancer. According to the CDC, Minnesota has the highest incidence of melanoma in Mid- west states. Despite advances in melanoma research, the five-year survival rate for patients with advanced Melanoma remains around 16%. Two therapeutic agents, vemurafenib, and dabrafenib, are FDA-approved for the treatment of advanced melanomas that carry BRAFV600E mutations. Although the initial response to these inhibitors can be dramatic, the melanomas nearly always become resistant. A novel mouse model of melanoma, we have developed that provides an exceptional experimental system to study this issue.
Targeting Chromosome Instability and the cGAS-STING Network in Pediatric Mid-Line Gliomas-K27M Mutant:
The major goal of this project is to understand how mutations in a H3.3 gene contribute to the generation of pediatric gliomas in collaboration with Dr. Hinchcliffe. This work and is funded by a grant from Department of Defense Rare Cancers Research Program.
Determination and validation of resistance mechanisms in melanoma:
This project aims to determine the mechanisms of resistance to MEK and BRAF inhibition; validate resistance mechanisms that drive the recurrence of melanomas; and pre-clinical validation of coordinated therapies. This work is funded by an American Cancer Society, Research Scholar Grant.
The role of APC mutations in melanoma brain metastasis:
The major goal of this project is to determine the role of dysregulated Wnt signaling in melanoma tumor immune microenvironment and metastasis. This project was recently funded (2022) by the Melanoma Research Alliance.
| 51 Mechanistic Dissection of the K27M Histone Mutation in Pediatric
Gliomagenesis:
Major Goal: To understand how mutations in a H3.3 gene contribute to the generation of pediatric gliomas. This work is funded by a Minnesota Partnership for Biotechnology and Medical Genomics Collaborative Research Grant
Histone methylation and chromosome instability in DIPG:
Major Goal: The specific goal of this pilot grant is to define the effect of loss of K27 methylation on S31 phosphorylation and chromosomal missegregation in H3.3 K27M and WT DIPG cells. This project is generously funded by a Paint the Town Pink Award which we hope will led to federal funding for this project in FY 2023.
 Recent Publications:
• Grigore, F., Yang, H., Hanson, N. D., VanBrocklin, M. W., Sarver, A. L., & Robinson, J. P. (2020). BRAF inhibition in melanoma is associated with the dysregulation of histone methylation and histone methyltransferases. Neoplasia, 22(9), 376-389.
• Yang, H., Kircher, D. A., Kim, K. H., Grossmann, A. H., VanBrocklin, M. W., Holmen, S. L., & Robinson, J. P. (2017). Activated MEK cooperates with Cdkn2a and Pten loss to promote the development and maintenance of melanoma. Oncogene, 36(27), 3842-3851.
• Shin, C. H., Grossmann, A. H., Holmen, S. L., & Robinson, J. P. (2015).
The BRAF kinase domain promotes the development of gliomas in vivo. Genes Cancer, 6(1-2), 9-18.
 Lab research activities:
https://www.hi.umn.edu/research/research-sections/ cell-signaling-and-tumorigenesis/
ORCID iD: https://orcid.org/0000-0002-6585-0116















































































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