Honors & Awards

  • AACR-Genentech Fellowship in Lung Cancer Research, American Association for Cancer Research, US (2017 - 2019)
  • University of California Postdoctoral Fellowship Award, Tobacco-Related Disease Research Program, University of California, US (2017 - 2019)
  • Stanford School of Medicine Dean’s Postdoctoral Fellowship, Stanford University, US (2017)
  • Washington Tunnicliffe Writing Fellowship, University of Washington, US (2016)
  • International Provost Grants, The State of Washington, US (2012 - 2013)
  • Washington Research Foundation Hall Fellowship, University of Washington, US (2011)
  • Studying Abroad Scholarship, Ministry of Education, Taiwan (2008 - 2010)
  • Excellent Paper Award, International Symposium on Bioengineering, Taiwan (2007)
  • National Taiwan University Presidential Award, Taiwan, National Taiwan University, Taiwan (2001 - 2002)

Professional Education

  • Bachelor of Arts, National Taiwan University (2005)
  • Master of Science, University of California Los Angeles (2010)
  • Doctor of Philosophy, University of Washington (2016)
  • Ph.D., University of Washington, Seattle, WA, US, Biology - Neuroscience (2016)
  • Master of Science, University of California, Los Angeles, CA, US, Biomedical Engineering (2010)

Stanford Advisors

Patents

  • Wen-Yang Lin, Ruoh-Huey Uang. "Taiwan Patent I378069 Method of Manufacturing Core-Shell Nanostructure", Industrial Technology Research Institute, Dec 1, 2012
  • Wen-Yang Lin, Ruoh-Huey Uang. "China P.Rep. Patent CN101837455B Method of Manufacturing Core-Shell Nanostructure", Industrial Technology Research Institute, Oct 26, 2011
  • Wen-Yang Lin, Ruoh-Huey Uang. "United States Patent US20100166976A1 Method of Manufacturing Core-Shell Nanostructure", Industrial Technology Research Institute, May 22, 2009

Contact

  • Academic
    annwylin@stanford.edu
    University - Scholar Department: Genetics Position: Postdoctoral Scholar

Additional Info

  • Mail Code: 5120

Links

Current Research and Scholarly Interests

Lung cancer is a major health burden, leading to more deaths than the next four major cancer types combined. Despite advances in clinical cancer genome sequencing and the development of many targeted therapies, understanding the relationship of tumor genotype to therapeutic response remains a major obstacle to translating existing drugs into effective cancer treatments in the clinic. Pharmacogenomic analysis of tumor response is often extrapolated from the analysis of patients' tumor responses or modeled using in vitro cultured cell line systems, but investigating the effect of tumor genotype on drug response in cell lines, patient-derived xenograft models, or patients themselves all have severe limitations. Genetically-engineered mouse models have emerged as particularly rigorous in vivo systems with which to test early stage oncology therapies and represent tractable models with which to investigate the impact of tumor genotype on therapy response. Current genetically-engineered mouse models are time-consuming, cost-intensive, and have unavoidable technical and experimental variability that has limited their use in translational studies.

We have established a novel multiplexed somatic genome-editing approach that will allow the quantification of genotype-specific drug responses. This in vivo approach will increase in precision and scope of translational cancer pharmacogenomics studies. To quantify the effect of tumor suppressor gene inactivation on lung cancer growth, we established a system that combines somatic Cas9-mediated gene inactivation with existing genetically-engineered mouse models to generate ~30 different lung tumor genotypes. To quantify the exact size of each tumor and determine the size distribution of each tumor genotype, we induce tumors with barcoded vectors and use high-throughput sequencing and statistical approaches to determine the number of cancer cells in each tumor. We will combine our quantitative pooled genome-editing approach with pre-clinical treatments to uncover genotype-specific therapy responses. We will quantify the responses of ~30 different genotypes of tumors to several therapies that have been shown to have genotype-specific effects in lung adenocarcinoma models. This will extend our understanding of the genomic modifiers of treatment responses and define the experimental and statistical parameters to enable the most efficient use of these models for translational studies. Finally, by performing pre-clinical/co-clinical trials for targeted therapies across >30 tumor genotypes in parallel we will generate a pharmacogenomic map connecting lung adenocarcinoma genotype to targeted therapy response. Our ongoing clinical interactions will allow validation of our pharmacogenomic predictions in lung adenocarcinoma patients.

This flexible system can incorporate additional tumor suppressors, allows for the investigation of genotype-specific responses to other therapies including immuno-therapies, and be adapted to other cancer types. The techniques described in this proposal are ideally positioned to become a mainstay of pre-clinical/co-clinical trial design.

Projects

  • A Quantitative Multiplexed Platform for the Pharmacogenomic Analysis of Lung Cancer, Stanford University (September 20, 2016 - September 19, 2019)

    Location

    Stanford, California

    Collaborators

All Publications

  • Functions of the SLC36 transporter Pathetic in growth control FLY Lin, W., Williams, C. R., Yan, C., Parrish, J. Z. 2015; 9 (3): 99-106

    Abstract

    Neurons exhibit extreme diversity in size, but whether large neurons have specialized mechanisms to support their growth is largely unknown. Recently, we identified the SLC36 transporter Pathetic (Path) as a factor required for extreme dendrite growth in neurons. Path is broadly expressed, but only neurons with large dendrite arbors or small neurons that are forced to grow large require path for their growth. To gain insight into the basis of growth control by path, we generated additional alleles of path and further examined the apparent specificity of growth defects in path mutants. Here, we confirm our prior finding that loss of path function imposes an upper limit on neuron growth, and additionally report that path likely limits overall neurite length rather than dendrite length alone. Using a GFP knock-in allele of path, we identify additional tissues where path likely functions in nutrient sensing and possibly growth control. Finally, we demonstrate that path regulates translational capacity in a cell type that does not normally require path for growth, suggesting that path may confer robustness on growth programs by buffering translational output. Altogether, these studies suggest that Path is a nutrient sensor with widespread function in Drosophila.

    View details for DOI 10.1080/19336934.2015.1129089

    View details for Web of Science ID 000373877400001

    View details for PubMedID 26735916

  • The SLC36 transporter Pathetic is required for extreme dendrite growth in Drosophila sensory neurons GENES & DEVELOPMENT Lin, W., Williams, C., Yan, C., Koledachkina, T., Luedke, K., Dalton, J., Bloomsburg, S., Morrison, N., Duncan, K. E., Kim, C. C., Parrish, J. Z. 2015; 29 (11): 1120-1135

    Abstract

    Dendrites exhibit enormous diversity in form and can differ in size by several orders of magnitude even in a single animal. However, whether neurons with large dendrite arbors have specialized mechanisms to support their growth demands is unknown. To address this question, we conducted a genetic screen for mutations that differentially affected growth in neurons with different-sized dendrite arbors. From this screen, we identified a mutant that selectively affects dendrite growth in neurons with large dendrite arbors without affecting dendrite growth in neurons with small dendrite arbors or the animal overall. This mutant disrupts a putative amino acid transporter, Pathetic (Path), that localizes to the cell surface and endolysosomal compartments in neurons. Although Path is broadly expressed in neurons and nonneuronal cells, mutation of path impinges on nutrient responses and protein homeostasis specifically in neurons with large dendrite arbors but not in other cells. Altogether, our results demonstrate that specialized molecular mechanisms exist to support growth demands in neurons with large dendrite arbors and define Path as a founding member of this growth program.

    View details for DOI 10.1101/gad.259119.115

    View details for Web of Science ID 000356174200003

    View details for PubMedID 26063572

  • Coordinate control of terminal dendrite patterning and dynamics by the membrane protein Raw DEVELOPMENT Lee, J., Peng, Y., Lin, W., Parrish, J. Z. 2015; 142 (1): 162-173

    Abstract

    The directional flow of information in neurons depends on compartmentalization: dendrites receive inputs whereas axons transmit them. Axons and dendrites likewise contain structurally and functionally distinct subcompartments. Axon/dendrite compartmentalization can be attributed to neuronal polarization, but the developmental origin of subcompartments in axons and dendrites is less well understood. To identify the developmental bases for compartment-specific patterning in dendrites, we screened for mutations that affect discrete dendritic domains in Drosophila sensory neurons. From this screen, we identified mutations that affected distinct aspects of terminal dendrite development with little or no effect on major dendrite patterning. Mutation of one gene, raw, affected multiple aspects of terminal dendrite patterning, suggesting that Raw might coordinate multiple signaling pathways to shape terminal dendrite growth. Consistent with this notion, Raw localizes to branch-points and promotes dendrite stabilization together with the Tricornered (Trc) kinase via effects on cell adhesion. Raw independently influences terminal dendrite elongation through a mechanism that involves modulation of the cytoskeleton, and this pathway is likely to involve the RNA-binding protein Argonaute 1 (AGO1), as raw and AGO1 genetically interact to promote terminal dendrite growth but not adhesion. Thus, Raw defines a potential point of convergence in distinct pathways shaping terminal dendrite patterning.

    View details for DOI 10.1242/dev.113423

    View details for Web of Science ID 000348240500021

    View details for PubMedID 25480915

  • PINK1-Parkin Pathway Activity Is Regulated by Degradation of PINK1 in the Mitochondrial Matrix PLOS GENETICS Thomas, R. E., Andrews, L. A., Burman, J. L., Lin, W., Pallanck, L. J. 2014; 10 (5)

    Abstract

    Loss-of-function mutations in PINK1, which encodes a mitochondrially targeted serine/threonine kinase, result in an early-onset heritable form of Parkinson's disease. Previous work has shown that PINK1 is constitutively degraded in healthy cells, but selectively accumulates on the surface of depolarized mitochondria, thereby initiating their autophagic degradation. Although PINK1 is known to be a cleavage target of several mitochondrial proteases, whether these proteases account for the constitutive degradation of PINK1 in healthy mitochondria remains unclear. To explore the mechanism by which PINK1 is degraded, we performed a screen for mitochondrial proteases that influence PINK1 abundance in the fruit fly Drosophila melanogaster. We found that genetic perturbations targeting the matrix-localized protease Lon caused dramatic accumulation of processed PINK1 species in several mitochondrial compartments, including the matrix. Knockdown of Lon did not decrease mitochondrial membrane potential or trigger activation of the mitochondrial unfolded protein stress response (UPRmt), indicating that PINK1 accumulation in Lon-deficient animals is not a secondary consequence of mitochondrial depolarization or the UPRmt. Moreover, the influence of Lon on PINK1 abundance was highly specific, as Lon inactivation had little or no effect on the abundance of other mitochondrial proteins. Further studies indicated that the processed forms of PINK1 that accumulate upon Lon inactivation are capable of activating the PINK1-Parkin pathway in vivo. Our findings thus suggest that Lon plays an essential role in regulating the PINK1-Parkin pathway by promoting the degradation of PINK1 in the matrix of healthy mitochondria.

    View details for DOI 10.1371/journal.pgen.1004279

    View details for Web of Science ID 000337145100002

    View details for PubMedID 24874806

  • Antioxidant effects of betulin on porcine chondrocyte behavior in gelatin/C6S/C4S/HA modified tricopolymer scaffold Materials Science and Engineering: C Lin, W., Lin, F., Sadhasivam, S., Savitha, S. 2010; 30 (4): 597–604

    View details for DOI 10.1016/j.msec.2010.02.010

  • The dose dependent effects of betulin on porcine chondrocytes Process Biochemistry Lin, W., Sadhasivam, S., Lin, F. 2009; 44 (6): 678–684

    View details for DOI 10.1016/j.procbio.2009.02.008