National Cancer Institute - Cancer.gov

Headshot of Mioara Larion

Mioara Larion, Ph.D.

  • Center for Cancer Research
  • National Cancer Institute
Investigator
Neuro-Oncology Branch
Head, Cancer Metabolism Research Program

RESEARCH SUMMARY

Dr. Larion is a trained biochemist who leads the Cancer Metabolism Research Program at the Neuro-Oncology Branch (NOB). She is interested in the metabolic needs of cancer cells and how they process nutrients, in order to develop targeted approaches that delay tumor growth. She utilizes a set of technologies, including Raman imaging microscopy and metabolomics, to quantify patterns in proteins, lipids, and nucleic acids levels at subcellular resolution. This is a very important endeavor for glioma tumors, which are known to exhibit high heterogeneity.

Dr. Larion’s lab is specifically focused on identifying metabolic vulnerabilities in IDH1-mutated gliomas for clinical application, as well as developing technologies that enable these discoveries. Her lab has shown that lipid pathways are important for IDH1-mutant glioma growth, and that targeting specific enzymes from either fatty acid synthesis or sphingolipid pathway leads to specific cellular death in these cells. She is also interested in developing biomarkers to help image disease progression and monitor patients’ response to treatment.

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Areas of Expertise

Cancer Metabolism
Imaging Cancer (Cellular and Clinical)
Brain and Spine Cancer
IDH1-Mutated Gliomas
Raman Spectroscopy
Metabolomics and Lipidomics

Research

Diagram of various types of Raman spectroscopy

As head of the the Cancer Metabolism Research Program at the Neuro-Oncology Branch (NOB), Dr. Larion observes the direct impact that cancer metabolism has on patient diagnosis, treatment, and outcomes. Because IDH mutations cause metabolic reprogramming, Dr. Larion’s research focuses on exploiting this phenomenon for therapeutic development and imaging studies that aid early diagnosis. Dr. Larion’s laboratory has shown that lipid pathways are important for IDH1-mutant glioma growth, and that targeting specific enzymes from either fatty acid synthesis or the sphingolipid pathway leads to specific cellular death in these cells (see figure).

Intracellular proteins, lipids, and nucleic acids can be quantified at the level of cells and individual organelles using Raman spectroscopy, which Dr. Larion leveraged for this project. Capturing changes in these molecules exposes the intrinsic vulnerabilities of IDH-mutant glioma cells. Studying this disease from various angles leads to better diagnostic, surgical, and therapeutic benefits for patients. Dr. Larion's research could also help create a “metabolomic map," outlining each patient's nutrient availability, mutational profile, and metabolic dependency.

Publications

Selected Publications

Advances in measuring cancer cell metabolism with subcellular resolution

Ruiz-Rodado V, Lita A, Larion M
Nature Methods. 19(9): 1048-1063, 2022. [ Journal Article ]

IDH1 mutations induce organelle defects via dysregulated phospholipids.

Lita A, Pliss A, Kuzmin A, Yamasaki T, Zhang L, Dowdy T, Burks C, de Val N, Celiku O, Ruiz-Rodado V, Nicoli ER, Kruhlak M, Andresson T, Das S, Yang C, Schmitt R, Herold-Mende C, Gilbert MR, Prasad PN, Larion M
Nature Communications. 12(1): 614, 2021. [ Journal Article ]

Sphingolipid Pathway as a Source of Vulnerability in IDH1mut Glioma.

Dowdy T, Zhang L, Celiku O, Movva S, Lita A, Ruiz-Rodado V, Gilbert MR, Larion M
Cancers. 12(10): 2910, 2020. [ Journal Article ]

Metabolic Reprogramming Associated with Aggressiveness Occurs in the G-CIMP-High Molecular Subtypes of IDH1mut Lower Grade Gliomas

Ruiz-Rodado V, Malta TM, Seki T, Lita A, Dowdy T, Celiku O, Cavazos-Saldana A, Li A, Liu Y, Han S, Zhang W, Song H, Davis D, Lee S, Trepel JB, Sabedot TS, Munasinghe J, Yang C, Herold-Mende C, Gilbert MR, Krishna Cherukuri M, Noushmehr H, Larion M
Neuro-Oncology. 22(4): 480-492, 2020. [ Journal Article ]

Toward Single-Organelle Lipidomics in Live Cells.

Lita, A, Kuzmin, AN, Pliss, A, Baev, A, Rzhevskii, A, Gilbert, MR, Larion, M
Analytical Chemistry. 91(17): 11380-87, 2019. [ Journal Article ]

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Team

Scientist I
Lumin Zhang, Ph.D.
Visiting Fellow
Helena Muley Vilamú, Ph.D.
Laboratory Technician
Tyrone M. Dowdy