Aaron Meyer *
Department of Bioengineering at UCLA
4121G Engineering V
Los Angeles, CA 90095
Member, Bioinformatics GPB Home Area
Mapping Mechanisms of Resistance in Cancer
Targeted therapies extend many cancer patients’ lives but are limited in efficacy to a subset of patients and by the development of resistance. Efforts undertaken to identify mechanisms of resistance have uncovered numerous changes involving gene expression, post-translational regulation, and even tumor-extrinsic factors such as host-derived growth factors. Combination therapy can effectively combat resistance but requires accurate identification of the relevant resistance mechanism. Precision therapy must account for many genetic and non-genetic intrinsic and adaptive resistance mechanisms if it will accurately select these combinations.
Projects in the lab include mapping the common essential signaling events that drive resistance, quantifying single cell heterogeneity in drug response, and exploring how the extracellular matrix environment directs resistance development.
Systems Approaches for Rational Immune Therapies
Many immune receptors operate as families with multiple ligands and receptors, expressed across diverse cell populations. The lab’s efforts operate around the central hypothesis that the multiple members of these families are present to perform computation-like regulation across cell populations. Further, we can use engineering analysis tools to measure and manipulate these systems.
We are studying regulation of families like the Tyro3, AXL, MerTK (TAM) tyrosine kinases, Fcγ, and common γ-chain cytokine receptors. In addition to studying how these receptors operate as a family, we are working to develop tools that make visualizing and manipulating family-wide behavior easier.
Aaron Meyer is an assistant professor in the Department of Bioengineering at the University of California, Los Angeles. He received his B.S. in Bioengineering from the University of California, Los Angeles, his Ph.D. in Biological Engineering from the Massachusetts Institute of Technology, and was an independent fellow at the Koch Institute for Integrative Cancer Research. His awards include the NIH Director’s Early Independence Award, Siebel Scholars award, and a Terri Brodeur Breast Cancer Foundation Fellowship.
A selected list of publications:
- Robinett Ryan A, Guan Ning, Lux Anja, Biburger Markus, Nimmerjahn Falk, Meyer Aaron S Dissecting FcγR Regulation through a Multivalent Binding Model Cell systems, 2018; 7(1): 41-48.e5.
- Muffat Julien, Li Yun, Omer Attya, Durbin Ann, Bosch Irene, Bakiasi Grisilda, Richards Edward, Meyer Aaron, Gehrke Lee, Jaenisch Rudolf Human induced pluripotent stem cell-derived glial cells and neural progenitors display divergent responses to Zika and dengue infections Proceedings of the National Academy of Sciences of the United States of America, 2018; 115(27): 7117-7122.
- Schwartz Alyssa D, Barney Lauren E, Jansen Lauren E, Nguyen Thuy V, Hall Christopher L, Meyer Aaron S, Peyton Shelly R A biomaterial screening approach reveals microenvironmental mechanisms of drug resistance Integrative biology : quantitative biosciences from nano to macro, 2017; 9(12): 912-924.
- Zweemer Annelien J M, French Cory B, Mesfin Joshua, Gordonov Simon, Meyer Aaron S, Lauffenburger Douglas A Apoptotic Bodies Elicit Gas6-Mediated Migration of AXL-Expressing Tumor Cells Molecular cancer research : MCR, 2017; 15(12): 1656-1666.
- Archer Tenley C, Fertig Elana J, Gosline Sara J C, Hafner Marc, Hughes Shannon K, Joughin Brian A, Meyer Aaron S, Piccolo Stephen R, Shajahan-Haq Ayesha N Systems Approaches to Cancer Biology Cancer research, 2016; 76(23): 6774-6777.
- Manole Simin, Richards Edward J, Meyer Aaron S JNK Pathway Activation Modulates Acquired Resistance to EGFR/HER2-Targeted Therapies Cancer research, 2016; 76(18): 5219-28.
- McConnell Russell E, Edward van Veen J, Vidaki Marina, Kwiatkowski Adam V, Meyer Aaron S, Gertler Frank B A requirement for filopodia extension toward Slit during Robo-mediated axon repulsion The Journal of cell biology, 2016; 213(2): 261-74.
- Miller Miles A, Oudin Madeleine J, Sullivan Ryan J, Wang Stephanie J, Meyer Aaron S, Im Hyungsoon, Frederick Dennie T, Tadros Jenny, Griffith Linda G, Lee Hakho, Weissleder Ralph, Flaherty Keith T, Gertler Frank B, Lauffenburger Douglas A Reduced Proteolytic Shedding of Receptor Tyrosine Kinases Is a Post-Translational Mechanism of Kinase Inhibitor Resistance Cancer discovery, 2016; 6(4): 382-99.
- Miller Miles A, Moss Marcia L, Powell Gary, Petrovich Robert, Edwards Lori, Meyer Aaron S, Griffith Linda G, Lauffenburger Douglas A Targeting autocrine HB-EGF signaling with specific ADAM12 inhibition using recombinant ADAM12 prodomain Scientific reports, 2015; 5(4): 15150.
- Riquelme Daisy N, Meyer Aaron S, Barzik Melanie, Keating Amy, Gertler Frank B Selectivity in subunit composition of Ena/VASP tetramers Bioscience reports, 2015; 35(5): 15150.
- Meyer Aaron S, Zweemer Annelien J M, Lauffenburger Douglas A The AXL Receptor is a Sensor of Ligand Spatial Heterogeneity Cell systems, 2015; 1(1): 25-36.
- Meyer Aaron S, Miller Miles A, Gertler Frank B, Lauffenburger Douglas A The receptor AXL diversifies EGFR signaling and limits the response to EGFR-targeted inhibitors in triple-negative breast cancer cells Science signaling, 2013; 6(287): ra66.
- Miller Miles A, Meyer Aaron S, Beste Michael T, Lasisi Zainab, Reddy Sonika, Jeng Karen W, Chen Chia-Hung, Han Jongyoon, Isaacson Keith, Griffith Linda G, Lauffenburger Douglas A ADAM-10 and -17 regulate endometriotic cell migration via concerted ligand and receptor shedding feedback on kinase signaling Proceedings of the National Academy of Sciences of the United States of America, 2013; 110(22): E2074-83.
- Meyer Aaron S, Hughes-Alford Shannon K, Kay Jennifer E, Castillo Amalchi, Wells Alan, Gertler Frank B, Lauffenburger Douglas A 2D protrusion but not motility predicts growth factor-induced cancer cell migration in 3D collagen The Journal of cell biology, 2012; 197(6): 721-9.
- Kim Hyung-Do, Meyer Aaron S, Wagner Joel P, Alford Shannon K, Wells Alan, Gertler Frank B, Lauffenburger Douglas A Signaling network state predicts twist-mediated effects on breast cell migration across diverse growth factor contexts Molecular & cellular proteomics : MCP, 2011; 10(11): M111.008433.
- Mashayekhi Foad, Meyer Aaron S, Shiigi Stacey A, Nguyen Vu, Kamei Daniel T Concentration of mammalian genomic DNA using two-phase aqueous micellar systems Biotechnology and bioengineering, 2009; 102(6): 1613-23.