Honors & Awards

  • Stanford Graduate Fellowship, Vice Provost for Graduate Education, Stanford University (2018-2021)
  • Leave Term Grant (Kaminsky Academic Enrichment Award), Dartmouth College (2017)
  • William H. Neukom 1964 Scholar, Neukom Institute, Dartmouth College (2017)
  • James O. Freedman Presidential Scholar, Dartmouth College (2016)
  • Sophomore Science Scholar (Bingham Undergraduate Research Award), Dartmouth College (2016)

Professional Affiliations and Activities

  • Associate Member, American Association for Cancer Research (2018 - Present)
  • Student Member, Society for Neuro-Oncology (2018 - 2019)
  • Associate Member, Sigma Xi (2018 - Present)

Membership Organizations

Education & Certifications

  • M.S., Stanford University, Cancer Biology (2021)
  • A.B., Dartmouth College, Biology (High Honors) (2018)

All Publications

  • The AMBRA1 E3 ligase adaptor regulates the stability of cyclinD. Nature Chaikovsky, A. C., Li, C., Jeng, E. E., Loebell, S., Lee, M. C., Murray, C. W., Cheng, R., Demeter, J., Swaney, D. L., Chen, S., Newton, B. W., Johnson, J. R., Drainas, A. P., Shue, Y. T., Seoane, J. A., Srinivasan, P., He, A., Yoshida, A., Hipkins, S. Q., McCrea, E., Poltorack, C. D., Krogan, N. J., Diehl, J. A., Kong, C., Jackson, P. K., Curtis, C., Petrov, D. A., Bassik, M. C., Winslow, M. M., Sage, J. 2021


    The initiation of cell division integrates a large number of intra- and extracellular inputs. D-type cyclins (hereafter, cyclinD) couple these inputs to the initiation of DNA replication1. Increased levels of cyclinD promote cell division by activating cyclin-dependent kinases4 and 6 (hereafter, CDK4/6), which in turn phosphorylate and inactivate the retinoblastoma tumour suppressor. Accordingly, increased levels and activity of cyclinD-CDK4/6 complexes are strongly linked to unchecked cell proliferation and cancer2,3. However, the mechanisms that regulate levels of cyclinD are incompletely understood4,5. Here we show that autophagy and beclin1 regulator1 (AMBRA1) is the main regulator of the degradation of cyclinD. We identified AMBRA1 in a genome-wide screen to investigate the genetic basis of the response to CDK4/6 inhibition. Loss of AMBRA1 results in high levels of cyclinD in cells and in mice, which promotes proliferation and decreases sensitivity to CDK4/6 inhibition. Mechanistically, AMBRA1 mediates ubiquitylation and proteasomal degradation of cyclinD as a substrate receptor for the cullin4 E3 ligase complex. Loss of AMBRA1 enhances the growth of lung adenocarcinoma in a mouse model, and low levels of AMBRA1 correlate with worse survival in patients with lung adenocarcinoma. Thus, AMBRA1 regulates cellular levels of cyclinD, and contributes to cancer development and the response of cancer cells to CDK4/6 inhibitors.

    View details for DOI 10.1038/s41586-021-03474-7

    View details for PubMedID 33854239

  • Cells of origin of lung cancers: lessons from mouse studies. Genes & development Ferone, G., Lee, M. C., Sage, J., Berns, A. 2020; 34 (15-16): 1017–32


    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 also capable of showing features of multiple subtypes or converting from one subtype to another. The intertumoral and intratumoral heterogeneity of lung cancers as well as incidences of subtype transdifferentiation raise the question of to what extent the tumor characteristics are dictated by the cell of origin rather than the acquired driver lesions. We provide here an overview of the studies in experimental mouse models that try to address this question. These studies convincingly show that both the cell of origin and the genetic driver lesions play a critical role in shaping the phenotypes of lung tumors. However, they also illustrate that there is far from a direct one-to-one relationship between the cell of origin and the cancer subtype, as most epithelial cells can be reprogrammed toward diverse lung cancer fates when exposed to the appropriate set of driver mutations.

    View details for DOI 10.1101/gad.338228.120

    View details for PubMedID 32747478

  • Unbiased Proteomic Profiling Uncovers a Targetable GNAS/PKA/PP2A Axis in Small Cell Lung Cancer Stem Cells. Cancer cell Coles, G. L., Cristea, S. n., Webber, J. T., Levin, R. S., Moss, S. M., He, A. n., Sangodkar, J. n., Hwang, Y. C., Arand, J. n., Drainas, A. P., Mooney, N. A., Demeter, J. n., Spradlin, J. N., Mauch, B. n., Le, V. n., Shue, Y. T., Ko, J. H., Lee, M. C., Kong, C. n., Nomura, D. K., Ohlmeyer, M. n., Swaney, D. L., Krogan, N. J., Jackson, P. K., Narla, G. n., Gordan, J. D., Shokat, K. M., Sage, J. n. 2020


    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 activated in a small subset of human SCLC, promotes SCLC development. Phosphoproteomic analyses identified many PKA substrates and mechanisms of action. In particular, PKA activity is required for the propagation of SCLC stem cells in transplantation studies. Broad proteomic analysis of recalcitrant cancers has the potential to uncover targetable signaling networks, such as the GNAS/PKA/PP2A axis in SCLC.

    View details for DOI 10.1016/j.ccell.2020.05.003

    View details for PubMedID 32531271

  • Characterizing the heterogeneity in 5-aminolevulinic acid-induced fluorescence in glioblastoma. Journal of neurosurgery Almiron Bonnin, D. A., Havrda, M. C., Lee, M. C., Evans, L., Ran, C., Qian, D. C., Harrington, L. X., Valdes, P. A., Cheng, C., Amos, C. I., Harris, B. T., Paulsen, K. D., Roberts, D. W., Israel, M. A. 2019: 1–9


    OBJECTIVE5-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 progression-free survival. The heterogeneity of 5-ALA-induced PpIX fluorescence observed during surgery presents a technical and diagnostic challenge when utilizing this tool intraoperatively. While some regions show bright fluorescence after 5-ALA administration, other regions do not, despite that both regions of the tumor may be histopathologically indistinguishable. The authors examined the biological basis of this heterogeneity using computational methods.METHODSThe authors collected both fluorescent and nonfluorescent GBM specimens from a total of 14 patients undergoing surgery and examined their gene expression profiles.RESULTSIn this study, the authors found that the gene expression patterns characterizing fluorescent and nonfluorescent GBM surgical specimens were profoundly different and were associated with distinct cellular functions and different biological pathways. Nonfluorescent tumor tissue tended to resemble the neural subtype of GBM; meanwhile, fluorescent tumor tissue did not exhibit a prominent pattern corresponding to known subtypes of GBM. Consistent with this observation, neural GBM samples from The Cancer Genome Atlas database exhibited a significantly lower fluorescence score than nonneural GBM samples as determined by a fluorescence gene signature developed by the authors.CONCLUSIONSThese results provide a greater understanding regarding the biological basis of differential fluorescence observed intraoperatively and can provide a basis to identify novel strategies to maximize the effectiveness of fluorescence agents.

    View details for DOI 10.3171/2019.2.JNS183128

    View details for PubMedID 31125970

  • Secretion-mediated STAT3 activation promotes self-renewal of glioma stem-like cells during hypoxia ONCOGENE Bonnin, D., Havrda, M. C., Lee, M. C., Liu, H., Zhang, Z., Nguyen, L. N., Harrington, L. X., Hassanpour, S., Cheng, C., Israel, M. A. 2018; 37 (8): 1107–18


    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-like cells. A defining characteristic of these cancer stem-like cells is their capacity to self-renew. We have identified a hypoxia-induced pathway that utilizes the Hypoxia Inducible Factor 1α (HIF-1α) transcription factor and the JAK1/2-STAT3 (Janus Kinase 1/2 - Signal Transducer and Activator of Transcription 3) axis to enhance the self-renewal of glioma stem-like cells. Hypoxia is a commonly found pathologic feature of HGGs. Under hypoxic conditions, HIF-1α levels are greatly increased in glioma stem-like cells. Increased HIF-1α activates the JAK1/2-STAT3 axis and enhances tumor stem-like cell self-renewal. Our data further demonstrate the importance of Vascular Endothelial Growth Factor (VEGF) secretion for this pathway of hypoxia-mediated self-renewal. Brefeldin A and EHT-1864, agents that significantly inhibit VEGF secretion, decreased stem cell self-renewal, inhibited tumor growth, and increased the survival of mice allografted with S100β-v-erbB/p53-/- glioma stem-like cells. These agents also inhibit the expression of a hypoxia gene expression signature that is associated with decreased survival of HGG patients. These findings suggest that targeting the secretion of extracellular, autocrine/paracrine mediators of glioma stem-like cell self-renewal could potentially contribute to the treatment of HGGs.

    View details for DOI 10.1038/onc.2017.404

    View details for Web of Science ID 000425905700013

    View details for PubMedID 29155422

    View details for PubMedCentralID PMC5851110