Page 19 - Hormel Institute Annual Report 2021-22
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     Current research projects:
1) Structural Characterization and Function of Sphingolipid Transfer Proteins in Eukaryotes
2) The Functional Role of the cPLA2α/C1P Interaction in Sepsis Resolution
3) Inflammation in Breast Cancer Initiation and Progression: Intervention Potential by Sphingolipid Transfer Proteins
4) Regulation of Ceramide-1-Phosphate Transfer Protein (CPTP): New Strategy for Enhancing Breast Cancer Therapeutics
Generation of small, homogeneour single-bilayer POPC vesicles by POPC/DHPC bicelle mix dilution
Research Support: Longstanding support by NIGMS-GM45228 and the Hormel Foundation; additional support by NCI- CA121493, NHLBI-HL08214, NHLBI-HL125353 and Paint the Town Pink.
Collaborators: D.J. Patel, (Memorial Sloan Kettering Cancer Center), Charles Chalfant, (Univ. Virginia), L. Malinina, (CIC bioGUNE, Derio/Bilbao, Spain),
ics, Annual Reviews of Biochemistry, ASBMB TODAY, and Progress in Lipid Research. The findings could ultimately facilitate use of GLTP superfamily proteins as nano-devices for targeted manipulation of cellular sphingolipid levels to regulate different programmed cell death processes, thus enabling novel therapeutic approaches for selectively destroying cancer cells or treating other diseases.
In eLife, we recently provided insights into the selection mechanism used by cPLA2α C2-domain to target phosphatidylcholine (PC) in membranes for arachidonic acid release. The findings could help develop new treatments for wound-healing, sepsis, and other inflammation-associated pathologic conditions including cancer.
Our research has also led to technological advances that simplify in vitro production of uniform-size membrane vesicles useful for measuring membrane interaction by lipid transfer proteins and other amphitropic proteins. In Analytical Chemistry, we reported spontaneous formation of uniform-size, stable lipid vesicles upon dilution of lipid membrane discs (bicelles) and provided detailed methodology
in Bio-protocol. Included are the first published images utilizing the Hormel Institute’s Cryo-Electron Micro- scope. The broad-reaching potential of our discovery has led to patent filing by the UMN Technology Com- mercialization Office.
J.G. Molotkovsky, (Shemyakin Institute of Bioogranic Chemistry, Russian Academy of Science), John Mundy (Univ. Copenhagen), Ted Hinchcliffe and Amer Alam, (UMN-Hormel Institute).
  Lab research activities:
https://www.hi.umn.edu/research/faculty/ rhoderick-e-brown-phd
ORCID iD:
https://orcid.org/0000-0002-7337-3604
  Ceramide-1-phosphate transfer protein (CPTP) with bound C1P interacting membrane containing PIP2
Top Publications:
• Mishra, S. K., Gao, Y. G., Zou, X., Stephenson, D. J., Malinina, L., Hinchcliffe, E. H., Chalfant, C. E., & Brown, R. E. (2020). Emerging roles for human glycolipid transfer protein superfamily members in the regulation of autophagy, inflammation, and cell death. Prog Lipid Res, 78, 101031.
• Malinina, L., Patel, D. J., & Brown, R. E. (2017). How α-Helical Motifs Form Functionally Diverse Lipid-Binding Compartments. Annu Rev Biochem, 86, 609-636.
• Simanshu, D. K., Kamlekar, R. K., Wijesinghe, D. S., Zou, X., Zhai, X., Mishra, S. K., Molotkovsky, J. G., Malinina, L., Hinchcliffe, E. H., Chalfant, C. E., Brown, R. E., & Patel, D. J. (2013). Non-vesicular trafficking by a ceramide-1-phosphate transfer protein regulates eicosanoids. Nature, 500(7463), 463-467.
• Malinina, L., Malakhova, M. L., Teplov, A., Brown, R. E., & Patel, D. J. (2004). Structural basis for glycosphingolipid transfer specificity. Nature, 430(7003), 1048-1053.
• Brodersen, P., Petersen, M., Pike, H. M., Olszak,
B., Skov, S., Odum, N., Jørgensen, L. B., Brown, R. E., & Mundy, J. (2002). Knockout of Arabidopsis accelerated-cell-death11 encoding a sphingosine transfer protein causes activation of programmed cell death and defense. Genes Dev, 16(4), 490-502









































































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