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Lipid transfer play critical roles in maintaining lipid homeostasis, signaling, and organelle quality. The Banerjee Lab is uncovering the molecular mechanisms of newly identified lipid transfer pathways that regulate ferroptosis, membrane fluidity, and metabolic signaling. In parallel, we investigate previously unrecognized pathways that control cellular lipid abundance. We seek to understand how disruption of these processes contributes to aggressive cancers and neurological diseases, with the goal of enabling new therapeutic approaches.
Lipid transfer play critical roles in maintaining lipid homeostasis, signaling, and organelle quality. The Banerjee Lab is uncovering the molecular mechanisms of newly identified lipid transfer pathways that regulate ferroptosis, membrane fluidity, and metabolic signaling. In parallel, we investigate previously unrecognized pathways that control cellular lipid abundance. We seek to understand how disruption of these processes contributes to aggressive cancers and neurological diseases, with the goal of enabling new therapeutic approaches.
Direction 1: How do Lipid Transfer Proteins (LTPs) suppress ferroptosis? Ferroptosis is driven by peroxidation of oxidation-prone lipids, such as PUFA-phospholipids, and could be suppressed by lipidic antioxidants such as coenzyme Q. Metastatic cancer cells accumulate high levels of PUFA-phospholipids that support tumor progression. However, this metabolic state renders them susceptible to ferroptosis (Wang et al., 2025). Similarly, therapy-resistant cancer cells exhibit heightened sensitivity to ferroptosis (Hangauer et al., 2017). The Banerjee Lab is investigating how lipid transfer proteins (LTPs) protect cancer cells from ferroptosis by controlling the spatial and temporal distribution of oxidation-prone lipids.
Direction 2: Novel lipid sensing mechanisms at the endoplasmic reticulum (ER) and mitochondria. We are investigating two distinct mechanisms that sense the abundance of the lipid phosphatidylethanolamine (PE). This abundant yet biophysically unique phospholipid is central to lipid metabolism and autophagy. In these projects, we seek to understand how BLTP2 and PE regulate the ER-to-Golgi translocation and activation of the master regulator of lipid metabolism, SREBP. Moreover, we will use genome-wide CRISPR screens to identify new pathways that coordinate PE metabolism between the ER and mitochondria.
ER (magenta) and mitochondria (green)
Direction 3: Targeting lipid transfer and metabolism in cancer. We screened a publicly available database to identify three LTP proteins that promote the survival of many cancer cells originating from the breast, pancreas, and kidney. We seek to leverage our understanding of fundamental mechanisms to support anti-cancer therapeutic discovery targeting these LTPs using high-throughput drug screenings and oncology collaborations. The lab is also interested in identifying novel oxidoreductases that could be targeted to induce ferroptosis in cancer.
Direction 4: Decoding the cellular basis of neurological diseases caused by defects in PE metabolism. Mutations in PCYT2, disrupting PE biosynthesis in the ER, cause a type of Hereditary Spastic Paraplegia (Dash et al., 2025). On the other hand, disruption of PE biosynthesis in mitochondria causes Liberfarb syndrome (Peter MD et al., 2019), a disease characterized by neurodegeneration and musculoskeletal defects. The Banerjee Lab seeks to uncover the cellular basis of these disorders by investigating organelle-specific changes in the lipidome, proteome, and metabolome to identify mechanisms that restore cellular function and could be harnessed therapeutically.
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