School of Medicine


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  • Andrew Nager

    Andrew Nager

    Postdoctoral Research Fellow, Molecular and Cellular Physiology

    Current Research and Scholarly Interests A decade ago, a collection of multi-organ pediatric disorders was attributed to dysfunctional cilia; cell-surface organelles that mediate cell-to-cell communication. These disorders (termed ciliopathies) predispose patients to respiratory inflammation, diabetes, and cancer, and the elucidation of cilia functions inform these prevalent health problems. Reflecting the diverse symptoms of cilia diseases, cilia function throughout the body, and surprisingly, almost every cell type presents at least one cilium. Cilia house receptors and receive signals, but it is not known how signaling is regulated or transduced into the cell. Receptor trafficking provides a molecular entry point to this problem as the receptor mistrafficking is characteristic of ciliopathies. The goal of my research is to determine how receptor trafficking regulates cilia signaling, and to uncover novel roles of cilia in cell-to-cell communication.

    1. Receptor Trafficking and Bardet-Biedl Syndrome
    The ciliary membrane contains numerous G-protein coupled receptors (GPCRs) that, upon activation, are removed from the cilium. By live-cell imaging of ciliated epithelial cells, I found that two competing pathways remove activated GPCRs from cilia: retrieval back into the cell or secretion into extracellular vesicles. Importantly, in the ciliopathy Bardet-Biedl Syndrome (BBS), both pathways are misregulated. One branch of my research focuses on how BBS-associated proteins regulate receptor trafficking, and how receptor trafficking regulates signaling.

    2. Biogenesis of Extracellular Vesicles
    A second thrust of my research is to understand how extracellular vesicles are formed. Extracellular vesicles are widely observed in biology, and function both to dispose unwanted molecules and transfer messages to other cells. Mammals release extracellular vesicles by several distinct pathways, yet our molecular understanding is limited to highly-conserved components identified by yeast genetics. Although yeast genetics discovered the important ESCRT cascade, mammals have elaborated and, in some contexts deviated from, this mechanism. For instance, mammalian cells have evolved to use actin for releasing vesicles from cilia, microvilli, and the plasma membrane. Leveraging biochemical tools for studying cilia, I identified a network of actin motors (Myosin 6) and crosslinkers (Drebrin, alpha-Actinin-4) that sever extracellular vesicles from cilia. This research informs how mammals produce extracellular vesicles, and provides molecular tools to determine the physiologic functions of extracellular vesicles.

  • Yusuke Nakauchi M.D., Ph.D.

    Yusuke Nakauchi M.D., Ph.D.

    Postdoctoral Research Fellow, Stanford Cancer Center

    Current Research and Scholarly Interests From 2005 to 2010, my work as a clinical hematology fellow allowed me to experience first-hand how scientific advances that started in a laboratory can transform the lives of patients. While many of my patients were cured of their disease with allogeneic hematopoietic stem cell transplantation, underscoring the importance of anti-tumor immunotherapy in eradicating leukemia, I witnessed face-to-face their suffering from the long-term consequence of graft-versus-host disease (GVHD). This experience was ultimately what drove me to engage in research to discover novel therapies. For this reason, I embarked on a PhD program in 2010 to design antibody therapy to (i) target GVHD and (ii) target hematological malignancies. Under the mentorship of Professor Hiromitsu Nakauchi at the University of Tokyo, an international leader in hematopoiesis, I developed allele-specific anti-human leukocyte antigen (HLA) monoclonal antibodies for severe GVHD caused by HLA-mismatched hematopoietic stem cell transplantation (Nakauchi et al., Exp Hematol, 2015). This study was the first to find that anti-HLA antibodies can be used therapeutically against GVHD. That success gave me the motivation and confidence to further my research beyond targeting GVHD, to targeting leukemic stem cells through my current postdoctoral fellowship in the laboratory of Professor Ravindra Majeti, Department of Hematology at Stanford University.

    Many people suffer from leukemia each year, but we still don’t know how to completely cure it. Recent advances in sequencing technologies have tremendously improved our understanding of the underlying mutations that drive hematologic malignancies, although, the reality is that the majority of the mutations are not easily “druggable” and the discovery of these mutations has not yet made a significant impact in patient outcomes. I view this perhaps the most crucial challenges facing a translational cancer researcher like myself. My current research is a major step toward my long term goal to make personalized medicine a reality for patients with acute myeloid leukemia (AML) and other hematologic malignancies. Although my research is focused on targeting Ten-Eleven Translocation methylcytosine dioxygenase-2 (TET2) mutations, I anticipate it will lead to a better understanding of the cell context requirement for TET2 mutations in AML and help identify the critical cells to target to both prevent the development of de novo leukemia and halt relapse. It may also prove of value to understanding of the biology of a range of other cancers.