Aros, C. J., P. Vijayaraj, C. J. Pantoja, B. Bisht, L. K. Meneses, J. M. Sandlin, J. A. Tse, M. W. Chen, A. Purkayastha, D. W. Shia, J. M. S. Sucre, T. M. Rickabaugh, E. K. Vladar, M. K. Paul and B. N. Gomperts (2020). “Distinct Spatiotemporally Dynamic Wnt-Secreting Niches Regulate Proximal Airway Regeneration and Aging.” Cell Stem Cell. DOI: https://doi.org/10.1016/j.stem.2020.06.019.
Aros, C. J., M. K. Paul, C. J. Pantoja, B. Bisht, L. K. Meneses, P. Vijayaraj, J. M. Sandlin, B. France, J. A. Tse, M. W. Chen, D. W. Shia, T. M. Rickabaugh, R. Damoiseaux and B. N. Gomperts (2020). “High-Throughput Drug Screening Identifies a Potent Wnt Inhibitor that Promotes Airway Basal Stem Cell Homeostasis.” Cell Rep 30(7): 2055-2064 e2055. DOI: https://doi.org/10.1016/j.celrep.2020.01.059.
Proliferating Transitory T Cells with an Effector-like Transcriptional Signature Emerge from PD-1+ STem-like CD8+ T Cells during Chronic Infection. William h. Hudson, Julia Gensheimer, Masao Hashimoto, Warren J. Leonard, Haydn T. Kissik, Rafi Ahmed
Published: December 03, 2019* DOI: https://doi.org/10.1016/j.immuni.2019.11.002 https://www.cell.com/immunity/fulltext/S1074-7613(19)30460-1
Improved Titer and Gene Transfer by Lentiviral Vectors Using Novel, Small B-Globin Locus Control Region Elements
Richard A. Morgan, Mildred J. Unti, Bamidele Aleshe, Shantha Senadheera, Roger P. Hollis, Donald Kohn
Published: September 27, 2019. DOI: https://doi.org/10.1016/j.ymthe.2019.09.020 https://doi.org/10.1016/j.ymthe.2019.09.020
Enhanced In Vivo Delivery of Stem Cells using Microporous Annealed Particlae Scaffolds
Jaekyung Koh, Donald R. Griffin, Maani M. Archang, An-Chieh Feng, Thomas Horn, Michael Margolis, David Zalazar, Tatiana Segura, Philip O. Scumpia, Dino Di Carlo
First published: 13 August 2019 https://doi.org/10.1002/smll.201903147 https://doi.org/10.1002/smll.201903147
Pan-cancer Convergence to a Small-Cell Neuroendocrine Phenotype that Shares Susceptibilities with Hematological Malignancies Nikolas G. Balanis; Katherine M. Sheu; Favour N. Esedebe; Jiaoti Huang; Owen N. Witte; Thomas G. Graeber Cancer Cell/Volume 36, Issue 1, P17-34.E7, July 08, 2019 DOI: https://doi.org/10.1016/jccell.2019.06.005
Differential Metabolic Reprogramming by Zika Virus Promotes Cell Death in Human versus Mosquito Cells
Shivani K. Thaker, Travis Chapa, Gustavo Garcia, Jr., Danyang Gong, Ernst W. Schmid, Vaithilingaraja Arumugaswami, Ren Sun, Heather R. Christofk
Cell Metabolism 29,1-11 (2019), In press; https://doi.org/10/1016/j.cmet.2019.01.024
Yount, N.Y., Weaver, D.C., Lee, E.Y., Lee, M.W., Wang, H., Cha, L.C., Wong, G.C.L., Yeaman, M.R. A Unifying Structural Signature of Eukaryotic a-helical Host Defense Peptides. In press, Proc Natl Acad Sci USA (2019).
Helical antimicrobial peptides assemble into protofibril scaffolds that present ordered dsDNA to TLR9 Ernest Y. Lee, Changsheng Zhang, Jeremy Di Domizio, Fan Jin, Will Connell, Mandy Hung, Nicolas Malkoff, Veronica Veksler, Michel Gilliet, Pengyu Ren, Geread C. L. Wong
CXCL4 assembles DNA into pro-inflammatory liquid crystalline complexes to amplify interferon-a production in systemic sclerosis. Nature Communications (2019) Lande, R, Lee, E.Y., Palazzo, R., Pitraforte, I., Mattenberger, Y., Spadaro, F., Stefanantoni, K., Iannace, N., Dufour, A.M., Falchi, M., Bianco, M., Alvarez, M., Riccieri, V., Truchetet, M.-E., Wong, G.C.L., Chizzolini, C., Frasca, L.
Cell-Type-Specific Patterned Stimulus-Independent Neuronal Activity in the Drosophila Visual System during Synapse Formation
Orkun Akin; Bryce T. Bajar; Mehmet F. Keles; Mark A. Frye; S. Lawrence Zipursky
Published January 30, 2019 DOI: https://doi.org/10.2016/j.neuron.2019.01.008
Lentiviral Gene Therapy in HSCs Restores Lineage-Specific Foxp3 Expression and Suppresses Autoimmunity in a Mouse Model of IPEX Syndrome
Masiuk, KE; Laborada, J; Roncarolo, MG; Hollis, RP; Kohn, DB
Published: January 10 2019 DOI: https://doi.org/10.1016/j.stem.2018.12.003
Arnav Mehta, Yeon Joo Kim, Lidia Robert, Jennifer Tsoi, Begona Comin-Anduix, Beata Berent-Maoz, Alistair J. Cochran, James Economou, Paul C. Tumeh, Cristina Puig-Saus and Antoni Ribas: Immunotherapy resistance by inflammation-induced dedifferentiation DOI: 10.1158/2159-8290.CD-17-1178 (Co-First Author) http://cancerdiscovery.aacrjournals.org/content/early/2018/06/13/2159-8290.CD-17-1178
Drosophila and human FHOD family formins nucleate actin filaments Aanand A. Patel, Zeynep A. Oztug Durer,*, Aaron P. van Loon, Kathryn V. Bremer,and Margot E. Quinlan JBC Papers in Press. Published on November 10, 2017 as Manuscript M117.800888
Lee, M.W., Lee, E.Y., Lai, G.H. Kennedy, N.W., Posey, A.E., Xian, W., Ferguson A.L., Hill, R.B., Wong, G.C.L. Molecular motor Dnm1 synergistically induces membrane curvature to fa- cilitate mitochondrial fission. In press, ACS Central Science (2017). doi:10.1021/acscentsci.7b00338
De Anda, J.*, Lee, E.Y.*, Lee, C.K.*, Bennett, R.R., Ji, X., Soltani, S., Harrison, M.C., Baker, A.E., Luo, Y., Chou, T., O’Toole, G.A., Armani, A.M., Golestanian, R., Wong, G.C.L. High-speed “4D“ computational microscopy of bacterial surface motility. ACS Nano, 11(9), 9340-9351 (2017). doi: 10.1021/acsnano.7b04738 *Co-first authorship
Lee, E.Y., Takahashi, T., Curk, T., Dobnikar, J., Gallo, R.L., Wong, G.C.L. Crystallinity of double-stranded RNA-antimicrobial peptide complexes modulates Toll-Like receptor 3- mediated inflammation. In press, ACS Nano (2017). doi:10.1021/acsnano.7b05234
Neural Circuit-Specialized Astrocytes:Transcriptomic, Proteomic, Morphological, and Functional EvidenceHua Chai, Blanca Diaz-Castro,Eiji Shigetomi, …, Julian P. Whitelegge,Giovanni Coppola, Baljit S. KhakhNeuronNeuroResourceVolume 95, Issue 3, 2 August 2017, Pages 531–549.e9 Highlights:
•Multiple approaches were used to assess astrocyte diversity in two neural circuits
•Physiological and anatomical studies showed evidence for astrocyte functional diversity
•RNA-seq, proteomic, and cell marker analyses confirmed diversity
•Evidence is provided for brain neural-circuit-specialized astrocytes
AUTISM SPEAKS Weatherstone Predoctoral Fellow Recipient 2017
Under the mentorship of Shafali Jeste, at the University of California-Los Angeles, Ms. Tran will use noninvasive electroencephalography (EEG) to identify early differences in brain connectivity in infants at high familial risk for autism. Her study will also assess whether these differences can predict language development and autism symptom severity. This work aims to improve early identification and personalized interventions that can support and improve each child’s development.
Memory-Induced Chaos in Cardiac Excitation
Julian Landaw, Alan Garfinkel, James N. Weiss, and Zhilin Qu
Phys. Rev. Lett. 118, 138101 – Published 28 March 2017
Excitable systems display memory, but how memory affects the excitation dynamics of such systems remains to be elucidated. Here we use computer simulation of cardiac action potential models to demonstrate that memory can cause dynamical instabilities that result in complex excitation dynamics and chaos. We develop an iterated map model that correctly describes these dynamics and show that memory converts a monotonic first return map of action potential duration into a nonmonotonic one, resulting in a period-doubling bifurcation route to chaos.
New Transgenic Mouse Lines for Selectively Targeting Astrocytes and Studying Calcium Signals in Astrocyte Processes In Situ and In Vivo.
Srinivasan R, Lu TY, Chai H, Xu J, Huang BS, Golshani P, Coppola G, Khakh BS
Neuron. 2016 Dec 21;92(6):1181-1195. doi: 10.1016/j.neuron.2016.11.030. Epub 2016 Dec 8.
Genome-wide changes in lncRNA, splicing, and regional gene expression patterns in autism
Neelrrop N. Parikshak, Vivek Swarup, T. Grant Belgard, Manuel Irimia, Gokuk Ramaswami, Michael J. Gandal, Christopher Hartl, Virpi Leppa, Luis de la Torre Ubieta, Jerry Huang, Jennifer K. Lowe, Benjamin J. Blencowe, Steve Horvath, Daniel H. Geschwind
Nature Volume: 540, Pages: 423–427 Date published: (15 December 2016) DOI: doi:10.1038/nature20612
Lee, E.Y., Fulan, B., Wong, G.C.L., Ferguson, A. Mapping membrane activity in undiscovered peptide sequence space using machine learning. Accepted, PNAS (2016).
Realegeno, S., Kelly-Scumpia, K.M., Dang, A.T., Lu, J., Teles, R., Liu, P.T., Schenk, M., Lee, E.Y., Schmidt, N.W., Wong, G.C.L., Sarno, E.N., Rea, T.H., Ochoa, M.T., Pellegrini, M., Modlin, R.L. S100A12 is part of the antimicrobial network against Mycobacterium leprae in human macrophages. PLoS Pathogens, 12(6): e1005705 (2016). doi:10.1371/journal.ppat.1005705
Sankhagowit S., Lee E.Y., Wong G.C.L., Malmstadt N. Oxidation of membrane curvature-regulating phosphatidylethanolamine lipid results in formation of bilayer and cubic structures. Langmuir, 32(10): 2450–2457 (2016). doi:10.1021/acs.langmuir.5b04332
Lee E.Y., Lee C.K., Schmidt N.W., Jin F., Lande R., Curk T., Frenkel D., Dobnikar J., Gilliet M., Wong G.C.L., A review of immune amplification via ligand clustering by self-assembled liquid-crystalline DNA complexes. Advances in Colloid and Interface Science, 232: 17-24 (2016). doi:10.1016/j.cis.2016.02.003
“An Investigational Patch-based Convolutional Neural Network Model for the Detection of Clinically Significant Prostate Cancer using Multiparametric MRI”
Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma.
Jesse M. Zaretsky, B.S., Angel Garcia-Diaz, Ph.D., Daniel S. Shin, M.D., Helena Escuin-Ordinas, Ph.D., Willy Hugo, Ph.D., Siwen Hu-Lieskovan, M.D., Ph.D., Davis Y. Torrejon, M.D., Gabriel Abril-Rodriguez, M.Sc., Salemiz Sandoval, Ph.D., Lucas Barthly, M.Sc., Justin Saco, B.S., Blanca Homet Moreno, M.D., Riccardo Mezzadra, M.Sc., Bartosz Chmielowski, M.D., Ph.D., Kathleen Ruchalski, M.D., I. Peter Shintaku, Ph.D., Phillip J. Sanchez, Ph.D., Cristina Puig-Saus, Ph.D., Grace Cherry, R.N., N.P., Elizabeth Seja, B.A., Xiangju Kong, M.Sc., Jia Pang, B.S., Beata Berent-Maoz, Ph.D., Begoña Comin-Anduix, Ph.D., Thomas G. Graeber, Ph.D., Paul C. Tumeh, M.D., Ton N.M. Schumacher, Ph.D., Roger S. Lo, M.D., Ph.D., and Antoni Ribas, M.D., Ph.D.
N Engl J Med 2016; 375:819-829September 1, 2016DOI: 10.1056/NEJMoa160495
Background Approximately 75% of objective responses to anti-programmed death 1 (PD-1) therapy in patients with melanoma are durable, lasting for years, but delayed relapses have been noted long after initial objective tumor regression despite continuous therapy. Mechanisms of immune escape in this context are unknown. Methods We analyzed biopsy samples from paired baseline and relapsing lesions in four patients with metastatic melanoma who had had an initial objective tumor regression in response to anti-PD-1 therapy (pembrolizumab) followed by disease progression months to years later. Results Whole-exome sequencing detected clonal selection and outgrowth of the acquired resistant tumors and, in two of the four patients, revealed resistance-associated loss-of-function mutations in the genes encoding interferon-receptor-associated Janus kinase 1 (JAK1) or Janus kinase 2 (JAK2), concurrent with deletion of the wild-type allele. A truncating mutation in the gene encoding the antigen-presenting protein beta-2-microglobulin (B2M) was identified in a third patient. JAK1 and JAK2 truncating mutations resulted in a lack of response to interferon gamma, including insensitivity to its antiproliferative effects on cancer cells. The B2M truncating mutation led to loss of surface expression of major histocompatibility complex class I. Conclusions In this study, acquired resistance to PD-1 blockade immunotherapy in patients with melanoma was associated with defects in the pathways involved in interferon-receptor signaling and in antigen presentation. (Funded by the National Institutes of Health and others.).
Mehta, A. and Baltimore, D. MicroRNAs as regulatory elements in immune system logic. Nature Reviews Immunology. 16: 279-294. 2016.
Mehta, A., Mann, M., Zhao, J. L., Marinov, G. K., Majumdar, D., Garcia-Flores, Y., Du, X., Erikci, E., Chowdhury, K., and Baltimore, D. The microRNA-212/132 cluster regulates B cell development and apoptosis by targeting Sox4. Journal of Experimental Medicine. 212(10): 1679-92. 2015.
Mehta, A., Zhao, J. L., Sinha, N., Marinov, G. K., Mann, M., Kowalczyk, M. K., Galamidi, R. P., Du, X., Erikci, E., Regev, A., Chowdury, K., and Baltimore, D. The microRNA-132 and microRNA-212 cluster regulates hematopoietic stem cell maintenance and survival with age by buffering FOXO3 expression. Immunity. 42(6): 1021-1032. 2015.
Esther Nie was awarded the prestigious Eva Kavan Prize for Excellence in Research on the Brain on June 14, 2016
The Eva Mary Kavan Prize for Excellence in Research on the Brain was established in 1999 by a generous endowment from Dr. Eva Kavan. Dr. Kavan earned her doctorate degree in medicine at Charles University in her native Prague, Czechoslovakia. She came to UCLA in 1956 at a time when there were only five hospitals performing open-heart surgery with a heart-lung machine; UCLA had one of the first teams to do open-heart surgery in the West. Dr. Kavan was a pioneer in the administration of anesthesia, utilizing the electroencephalogram to perform important research on the effects of the heart-lung machine on brain function during open-heart operations. Dr. Kavan created this award to encourage a talented young scholar to pursue scientific research on the brain.
Dr. Stephen Young, a UCLA cardiologist and molecular geneticist who works on understanding mechanisms for human disease, has been elected to the National Academy of Sciences — one of the highest honors that can be bestowed on a scientist — in recognition of his “distinguished and continuing achievements in original research.”
The National Academy of Sciences announced today the election of 84 new members and 21 foreign associates from 14 countries.
Young, a distinguished professor of medicine and human genetics at the David Geffen School of Medicine at UCLA, focuses on two areas of research — plasma triglyceride metabolism and the role of nuclear envelope proteins in health and disease.
2016 Mar 24;165(1):165-79. doi: 10.1016/j.cell.2016.01.020. Epub 2016 Feb 25.A Stringent Systems Approach Uncovers Gene-Specific Mechanisms Regulating Inflammation. Tong AJ1, Liu X1, Thomas BJ1, Lissner MM1, Baker MR2, Senagolage MD2, Allred AL2, Barish GD2, Smale ST3.
MYC-induced reprogramming of glutamine catabolism supports optimal virus replication
Minh Thai, Shivani K. Thaker, Jun Feng, Yushen Du, Hailiang Hu, Ting Ting Wu, Thomas G. Graeber, Daniel Braas & Heather R. Christofk
Nature Communications 6, Article number: 8873 Published 12 November 2015
A review of immune amplification via ligand clustering by self-assembled liquid-crystalline DNA complexes.
Ernest Y. Lee, Calvin K. Lee, Nathan W. Schmidt, Fan Jin, Roberto Lande, Tine Curk, Daan Frenkel, Jure Dobnikar, Michel Gilleit, Gerard C.L.Wong
Advances in Colloid and Interface Science, 19 February 2016
The splicing regulator PTBP1 controls the activity of the transcription factor Pbx1 during neuronal differentiation.
Linares AJ, Lin CH, Damianov A, Adams KL, Novitch BG, Black DL.
Elife. 2015 Dec 24; 4. pii: e09268. doi: 10.755/elife.09268
Adam E. Singer, MPhil; Karl A. Lorenz, MD, MSHS Symptom Trends in the Last Year of Life From 1998 to 2010: a cohort study Ann Intern Med. 2015;162(3):175-18
O’Donnell KC, Vargas ME, Sagasti A. (2013) WldS and PGC-1 regulate mitochondrial transportand oxidation state after axonal injury. J Neurosci. 33(37):14778-90.
Parikshak NN, Luo R, Zhang A, Won H, Lowe JK, Chandran V, Horvath S, Geschwind DH. (2013) Integrative functional genomic analyses implicate specific molecular pathways and circuits in autism. Cell. Nov 21;155(5):1008-21
Ch’ng TH, Uzgil B, Lin P, Avliyakulov NK, O’Dell TJ, Martin KC. (2012) Activity-dependenttransport of the transcriptional coactivator CRTC1 from synapse to nucleus. Cell. 150(1):207-21
Arboleda VA, Lee H, Parnaik R, Fleming A, Banerjee A, Ferraz-de-Souza B, Délot EC, Rodriguez-Fernandez IA, Braslavsky D, Bergadá I, Dell’Angelica EC, Nelson SF, Martinez-Agosto JA, Achermann JC, Vilain E. (2012) Mutations in the PCNA-binding domain ofCDKN1C cause IMAGe syndrome. Nat Genet. 44(7):788-92.
Rudie JD, Hernandez LM, Brown JA, Beck-Pancer D, Colich NL, Gorrindo P, ThompsonPM, Geschwind DH, Bookheimer SY, Levitt P, Dapretto M. (2012) Autism-associated promoter variant in MET impacts functional and structural brain networks. Neuron. 75(5):904-15.
Kohn LA, Hao QL, Sasidharan R, Parekh C, Ge S, Zhu Y, Mikkola HK, Crooks GM. (2012) Lymphoid priming in human bone marrow begins before expression of CD10 withupregulation of L-selectin. Nat Immunol. 13(10):963-71.
Liu SY, Sanchez DJ, Aliyari R, Lu S, Cheng G. (2012). Systematic identification of type I andtype II interferon-induced antiviral factors. Proc Natl Acad Sci U S A. 109(11):4239-44.
Anderson ES, Lin CH, Xiao X, Stoilov P, Burge CB, Black DL. (2012) The cardiotonic steroiddigitoxin regulates alternative splicing through depletion of the splicing factors SRSF3and TRA2B. RNA. 18(5):1041-9.
Colby JB, Van Horn JD, Sowell ER. (2011).Quantitative in vivo evidence for broad regional gradients in the timing of white matter maturation during adolescence. Neuroimage. 54(1):25-31.
Martin WJ, Stewart LS, Tarpley JW. Animal models of neuropathic pain. In Zhizhong Z. Pan (Ed.), Methods in Molecular Medicine, Opiod Research (pp. 233-242). 2003. Totowa, NJ. Humana Press.
Yamin G, Glaser CB, Uversky VN, & Fink AL. Certain Metals Trigger Fibrillation of Methionine-oxidized a-synuclein. J Biol Chem. 278: 27630-27635, 2003.
Yamin G, Uversky VN, & Fink AL. Nitration inhibits fibrillation of human a-synuclein in vitro by formation of soluble oligomers. FEBS Lett. 542: 147-152, 2003.
Ernest Lee, PhD;Parinaz Abiri, PhD