Myung Chang Lee

Genentech

Small cell lung cancer (SCLC) is a lethal form of lung cancer. Here, we develop a quantitative multiplexed approach on the basis of lentiviral barcoding with somatic CRISPR-Cas9-mediated genome editing to functionally investigate candidate regulators of tumor initiation and growth in genetically engineered mouse models of SCLC. We found that naphth...

Intratumoral heterogeneity is a seminal feature of human tumors contributing to tumor progression and response to treatment. Current technologies are still largely unsuitable to accurately track phenotypes and clonal evolution within tumors, especially in response to genetic manipulations. Here, we developed epitopes for imaging using combinatorial...

Small cell lung cancer (SCLC) is a highly lethal form of lung cancer. The high mutation burden in SCLC cells makes it challenging to predict key drivers of SCLC from genome sequencing data, thereby hindering the identification of possible therapeutic targets. Here we develop a quantitative multiplexed approach based on lentiviral barcoding with som...

The retinoblastoma (RB) tumor suppressor is functionally inactivated in a wide range of human tumors where this inactivation promotes tumorigenesis in part by allowing uncontrolled proliferation. RB has been extensively studied, but its mechanisms of action in normal and cancer cells remain only partly understood. Here, we describe a new mouse mode...

Brain metastasis is a major cause of morbidity and mortality in cancer patients. Here we investigated mechanisms allowing small-cell lung cancer (SCLC) cells to grow in the brain. We show that SCLC cells undergo a cell state transition towards neuronal differentiation during tumor progression and metastasis, and that this neuronal mimicry is critic...

The initiation of cell division integrates a large number of intra- and extracellular inputs. D-type cyclins (hereafter, cyclin D) couple these inputs to the initiation of DNA replication¹. Increased levels of cyclin D promote cell division by activating cyclin-dependent kinases 4 and 6 (hereafter, CDK4/6), which in turn phosphorylate and inactivat...

As one of the most common forms of cancer, lung cancers present as a collection of different histological subtypes. These subtypes are characterized by distinct sets of driver mutations and phenotypic appearance, and they often show varying degrees of heterogenicity, aggressiveness, and response/resistance to therapy. Intriguingly, lung cancers are...

Using unbiased kinase profiling, we identified protein kinase A (PKA) as an active kinase in small cell lung cancer (SCLC). Inhibition of PKA activity genetically, or pharmacologically by activation of the PP2A phosphatase, suppresses SCLC expansion in culture and in vivo. Conversely, GNAS (G-protein α subunit), a PKA activator that is genetically...

OBJECTIVE 5-aminolevulinic acid (5-ALA)–induced protoporphyrin IX (PpIX) fluorescence is an effective surgical adjunct for the intraoperative identification of tumor tissue during resection of high-grade gliomas. The use of 5-ALA-induced PpIX fluorescence in glioblastoma (GBM) has been shown to double the extent of gross-total resection and 6-month...

Glioblastoma is the most common and deadly form of malignant primary brain tumor, with median survival of 15 months from diagnosis. Despite multimodal treatment combining radiotherapy, chemotherapy, and surgery, most glioblastomas develop resistance to therapy and recur. Malignant oligodendrocyte precursor cell (OPC)-like glioma stem-like cells (GS...

Glioblastomas (GBMs) are the most aggressive type of primary brain tumor in adults, the second leading cause of cancer-related death in children, and are incurable using currently available treatment modalities. GBMs are characterized by the presence of primitive glioma stem-like cell subpopulations that resist chemotherapy and sustain disease prog...

High-grade gliomas (HGGs) include the most common and the most aggressive primary brain tumor of adults and children. Despite multimodality treatment, most high-grade gliomas eventually recur and are ultimately incurable. Several studies suggest that the initiation, progression, and recurrence of gliomas are driven, at least partly, by cancer stem-...

As the energetic demands of humanity increase, more attention has been devoted to finding alternative sources of energy such as biofuels like ethanol. Ethanol holds promise as an easily sourced biofuel in light of recent advances in biochemical techniques and recombinant genetics; recent efforts in metabolic engineering have allowed for production...

Emerging evidence suggests that deregulation of complex cell-fate regulatory mechanisms in stem-like neural cells can contribute to the initiation, progression, and recurrence of glioma. Our laboratory recently reported that suppression of HEY1 activity by the dominant negative transcription factor Inhibitor of DNA Binding 2 (ID2) promoted gliomage...

Glioblastoma, a type of high-grade glioma, is the most common and the most aggressive primary brain tumor of adults. The median survival is 12-15 months. Despite multimodality treatment, most high-grade gliomas eventually recur and are ultimately incurable. Several studies suggest that the initiation, progression, and recurrence of gliomas are driv...

Glioblastoma (GBM) is the most aggressive and common form of primary brain tumor in adults, with a median survival of less than two years despite multimodality treatment. Fluorescence-guided neurosurgery using 5-aminolevulinic acid (5-ALA) has received increasing attention for helping achieve gross total tumor resection and improving the subsequent...

High-grade gliomas (HGG) are the most common primary brain tumors, and patients with these tumors have a poor prognosis. Despite multimodal treatment, most high-grade gliomas ultimately recur. Recent studies suggest that the cancer stem cells contribute to the progression and recurrence of gliomas. Therefore, elucidating the mechanism of glioma ste...