Roy Wollman
Roy Wollman
Professor
Email: rwollman@ucla.edu
Office: 540 Boyer Hall
Phone: (855) 810-0905
Website: wollmanlab.ucla.edu
Biography
Dr. Wollman’s training was highly interdisciplinary including statistics, biophysics, experimental biology. He is passionate about science, mentoring, and kite flying.
Research Interests
The Wollman lab studies information processing in intracellular and intercellular signaling networks in the presence of a high degree of single-cell variability. A particular focus is on the connection between gene expression and signaling dynamics at the single cell level.
Education
B.Sc, Biology, Tel Aviv University 2003
B.Sc, Statistics And Operation Research, Tel Aviv University 2003
Ph.D., Cell and Developmental Biology, University of California, Davis 2008
Selected Publications
Zhang T, Pilko A, Wollman R (2020) ‘Loci specific epigenetic drug sensitivity.’ Nucleic Acids Res, doi: 10.1093/nar/gkaa210 .PMID: 32246716 Foreman R, Wollman R (2020) ‘Mammalian gene expression variability is explained by underlying cell state.’ Mol Syst Biol, 16 (2): e9146. PMID: 32043799 Handly LN, Wollman R, “Wound-induced Ca2+ wave propagates through a simple release and diffusion mechanism”, Molecular Biology of the Cell, 28 (11): 1457-1466 (2017) . Yao J, Pilko A, Wollman R., “Distinct cellular states determine calcium signaling response”, Molecular Systems Biology, 12 (12): 894-904 (2016) . Handly LN, Pilko A, Wollman R (2015) ‘Paracrine communication maximizes cellular response fidelity in wound signaling.’ Elife, 4 (): e09652. PMID: 26448485 Selimkhanov J, Taylor B, Yao J, Pilko A, Albeck J, Hoffmann A, Tsimring L, Wollman R (2014) ‘Accurate information transmission through dynamic biochemical signaling networks.’ Science, 346 (6215): 1370-3. PMID: 25504722
Xinshu Grace Xiao
Xinshu Grace Xiao
Professor
Director of Bioinformatics Interdepartmental Ph.D. Program
Maria Rowena Endowed Chair in Biological Sciences
Email: gxxiao@ucla.edu
Office: 2000E TLSB
Phone: (310) 206-6522
Website: https://www.xiao-lab.org/
Biography
Dr. Xinshu (Grace) Xiao received her B.S. degree at Tsinghua University, Beijing, China. She then went to the Massachusetts Institute of Technology (MIT) for graduate studies. After receiving her Ph.D degree in the Division of Health Sciences and Technology (HST), a joint program by MIT and Harvard Medical School, Dr. Xiao continued at MIT for postdoctoral training in the Department of Biology. In 2008, Dr. Xiao joined the faculty at the University of California, Los Angeles. She is now the Maria R. Ross Endowed Professor of the Department of Integrative Biology and Physiology. She also serves as the Director of the Bioinformatics Interdepartmental Program.
Research Interests
Research in the Xiao lab aims to better understand transcriptome complexity in health and disease. A major surprise resulted from the Human Genome Project was that humans, even though as an apparently much complex organism with 100 trillion cells, have only 25,000 to 30,000 genes. In contrast, the roundworm, an organism with 960 cells, has ~19,000 genes. The number of genes does not scale proportionally with biological sophistication. Instead, the transcriptome (the collection of RNA molecules expressed from genes) in higher organisms is closely regulated such that one gene may produce different transcript isoforms in a cell type and developmental stage-specific manner. The Xiao lab studies transcriptome complexity focusing on RNA splicing, RNA modification and other post-transcriptional mechanisms. With both a computational (dry) lab and an experimental (wet) lab, they develop new bioinformatic methods and experimental systems to understand the regulation and function of transcriptome complexity, and apply these methods to neuropsychiatric disorders and cancer. The lab makes extensive use of second and third generation sequencing technologies in bulk tissues and single cells to drive methodology developments and biological discoveries.
Education
B.S., Tsingua University 1998
M.S., Biomedical/Mechanical Engineering, Massachusetts Institute of Technology 2000
Ph.D., Biomedical Engineering, Massachusetts Institute of Technology, Harvard Medical School 2004
Selected Publications
Tran SS, Zhou Q, Xiao X. Statistical inference of differential RNA-editing sites from RNA-sequencing data by hierarchical modeling. Bioinformatics, 36(9):2796-2804 (2020).
Cass AA, Xiao X. mountainClimber identifies alternative transcription start and polyadenylation sites in RNA-seq. Cell Systems, 9(4):393-400 (2019).
Tran SS, Jun HI, Bahn JH, Azghadi A, Ramaswami G, Van Nostrand EL, Nguyen TB, Hsiao YE, Lee C, Pratt GA, Martínez-Cerdeño V, Hagerman RJ, Yeo GW, Geschwind DH, Xiao X., “Widespread RNA editing dysregulation in brains from autistic individuals”, Nature Neuroscience, 22 (1): 25-36 (2019) .
Arefeen A, Xiao X, Jiang T., “DeepPASTA: deep neural network based polyadenylation site analysis”, Bioinformatics, 1-9 (2019) .
The Extracellular RNA Communication Consortium, “Establishing Foundational Knowledge and Technologies for Extracellular RNA Research”, Cell, 177 (2): 231-242 (2019) .
Yang EW, Bahn JH, Hsiao EY, Tan BX, Sun Y, Fu T, Zhou B, Van Nostrand EL, Pratt GA, Freese P, Wei X, Quinones-Valdez G, Urban AE, Graveley BR, Burge CB, Yeo GW, Xiao X.Allele-specific binding of RNA-binding proteins reveals functional genetic variants in the RNA., “Allele-specific binding of RNA-binding proteins reveals functional genetic variants in the RNA”, Nature Communications, 10 (1): 1-15 (2019) .
Quinones-Valdez G, Tran SS, Jun HI, Bahn JH, Yang EW, Zhan L, Brümmer A, Wei X, Van Nostrand EL, Pratt GA, Yeo GW, Graveley BR, Xiao X., “Regulation of RNA editing by RNA-binding proteins in human cells”, Communications Biology, 2 (19): 1-14 (2019) .
Cheung R, Insigne KD, Yao D, Burghard CP, Wang J, Hsiao YE, Jones EM, Goodman DB, Xiao X, Kosuri S., “A Multiplexed Assay for Exon Recognition Reveals that an Unappreciated Fraction of Rare Genetic Variants Cause Large-Effect Splicing Disruptions”, Molecular Cell, 73 (1): 183-194 (2019) .
Hsiao YE, Bahn JH, Yang Y, Lin X, Tran S, Yang EW, Quinones-Valdez G, Xiao X., “RNA editing in nascent RNA affects pre-mRNA splicing”, Genome Research, 28 (6): 812-823 (2018) .
Burkett ZD, Day NF, Kimball TH, Aamodt CM, Heston JB, Hilliard AT, Xiao X, White SA, “FoxP2 isoforms delineate spatiotemporal transcriptional networks for vocal learning in the zebra finch”, eLife, 23 (7): 1-35 (2018) .
Xia Yang
Xia Yang
Professor
Vice Chair, Molecular, Cellular and Integrative Physiology (MCIP) Interdepartmental Ph.D. Program and Computational and Systems Biology (CaSB) Interdepartmental Program
Email: xyang123@ucla.edu
Office: 2000C TLSB
Phone: (310) 206-1812
Website: https://yanglab.ibp.ucla.edu
Biography
Dr. Xia Yang received her Ph.D. in Molecular Genetics and Bioinformatics from Georgia State University and had postdoctoral training in Systems Genetics at UCLA. She was Senior Research Scientist at Rosetta Inpharmatics/Merck & Co. and Director of Systems Biology at Sage Bionetworks prior to returning to UCLA as a faculty member.
Research Interests
Our research focuses on developing and applying multitissue multiomics systems biology approaches to dissect the molecular networks underlying diverse complex diseases, ranging from cardiometabolic diseases to neurodegenerative and neurological disorders, and utilize the systems level networks to guide precision medicine. Through integration of genetic, transcriptional, epigenomic, proteomic, gut microbiota, and phenotypic data from human and rodent populations, we investigate how complex interactions between genetic and environmental risk factors perturb tissue- and cell-specific gene networks which in turn induce variations in disease susceptibility. Subsequently, we use the causal molecular networks of diseases as the basis for therapeutic target identification and biomarker discovery.
Education
B.S., Pharmacy, Shandong University 1993
Ph.D., Molecular Genetics/Bioinformatics, Georgia State University 2003
Selected Publications
Yang X. “Multi-tissue Multi-omics Systems Biology to Dissect Complex Diseases”. Trends in Molecular Medicine, 2020.
Liu W, Venugopal S, Majid S, Ahn IS, Diamante G, Hong J, Yang X*, Chandler SH*. “Single-cell RNA-seq Analysis of the Brainstem of Mutant SOD1 mice Reveals Perturbed Cell Types and Pathways of Amyotrophic Lateral Sclerosis”. Neurobiology of Disease, 141: 104877, 2020.
Rajbhandari P+, Arneson D+, Feng AC, Ahn IS, Diamante G, Zaghari N, Thomas BJ, Vergnes L, Lee SD, Reue K, Smale ST, Yang X, Tontonoz P. “Single Cell Analysis Reveals Immune Cell-Adipocyte Crosstalk Regulating the Transcription of Thermogenic Adipocytes”. eLife 8:e49501, 2019.
Zhang G, Byun HR, Ying Z, Blencowe M, Zhao Y, Hong J, Shu L, Gomez-Pinilla F, Yang X. “Differential Metabolic and Multi-tissue Transcriptomic Responses to Fructose Consumption among Genetically Diverse Mice”. BBA – Molecular Basis of Disease. 1866: 165569, 2020.
Shu L, Meng Q, Tsai B, Diamante G, Chen Y, Mikhail A, Luk H, Ritz B, Allard P, Yang X, “Prenatal Bisphenol A Exposure in Mice Induces Multi-tissue Multi-omics Disruptions Linking to Cardiometabolic Disorders”, Endocrinology, 160 : 409-429, 2019.
Arneson D, Zhuang Y, Byun HR, Ahn IS, Ying Z, Zhang G, Gomez-Pinilla F, Yang X, “Single Cell Molecular Alterations Reveal Pathogenesis and Targets of Concussive Brain Injury”, Nature Communications, 9 : 3894, 2018.
Emilsson V, llkov M, Lamb JR, Finkel N, Gudmundsson EF, Pitts R, Hoover H, Jennings LL, Horman SR, Aspelund T, Shu L, Trifonov V, Gudmundsdottir V, Sigurdsson S, Manolescu A, Zhu J, Lesley SA, To J, Zhang J, Harris TB, Launer LJ, Zhang B, Eiriksdottir G, Yang X, Smith AV, Orth AP, Gudnason V, “Coregulatory Networks of Human Serum Proteins Link Genetics to Disease”, Science, 361 : 769-773, 2018.
Kurt Z, Barrere-Cain R, LaGuardia J, Mehrabian JM, Pan C, Hui ST, Norheim F, Zhou Z, Hasin Y, Lusis AJ, Yang X, “Tissue-specific Pathways and Networks Underlying Sexual Dimorphism in Non-Alcoholic Fatty Liver Disease”, Biology of Sex Differences, 9 : 46- (2018) .
Krishnan KC, Kurt Z, Barrere-Cain R, Sabir S, Das A, Floyd R, Vergnes L, Zhao Y, Che N, Charugundla S, Qi H, Zhou Z, Meng Y, Pan C, Seldin MM, Norheim F, Hui S, Reue K, Lusis, AJ, Yang X., “Integration of Multi-omics Data from Mouse Diversity Panel Highlights Mitochondrial Dysfunction in Non-Alcoholic Fatty Liver Disease”, Cell Systems, 6 : 1-13, 2018.
Shu L, Chen KHK, Zhang G, Huan T, Kurt Z, Zhao Y, Codoni V, Tregouet DA, Yang J, Wilson JG, Luo X, Levy D, Lusis AJ, Liu S, Yang X, “Shared Genetic Regulatory Networks for Cardiovascular Disease and Type 2 Diabetes in Multi-ethnic Populations”, PLOS Genetics, 13 (9): e1007040, 2017.
Alan Garfinkel
Research Interests
Mathematical modeling of cellular and tissue electrophysiology. Analysis of data from experimental and clinical arrhythmias using techniques of nonlinear dynamics (“chaos theory”). Development of pharmacologic and electrophysiologic interventions to prevent or control arrhythmias.
Education
B.A., Math and Philosophy, Cornell University
Ph.D., Philosophy/Mathematics, Harvard University
Alan Grinnell
Biography
PhD Harvard, 1962; Junior Fellow, Harvard, 1959-62; postdoc UCLondon, 1962-64; UCLA faculty, 1964-present, Departments of Physiology (SOM) and Integrative Biology and Physiology IBP (College); Director, Jerry Lewis Neuromuscular Research Center, 1978-2001; Director, Ahmanson Laboratory of Neurobiology, 1979-2004; Chair, IBP Department 1997-2001; Associate Dean of Life Sciences for Personnel, 2010-
Research Interests
Adaptations of the auditory nervous system of echolocating bats that enable them to orient and hunt using echoes of emitted sounds as a substitute for vision. Also, bat echolocation behavior and feeding strategies. Trophic influences between nerve and muscle governing number, size and strength of nerve terminals. Regulation of neurotransmitter release and properties of presynaptic active zones.
Specific Recent Projects: a. Using Xenopus nerve-muscle cell cultures, patch electrode recordings can be made simultaneously from presynaptic varicosities and postsynaptic muscle cells. Large conductance Ca2+-dependent K+ (BK) channels that co-localize with Ca2+ channels at presynaptic active zones (AZs) can be used to report [Ca2+] at AZs and correlate this direct measurement with neurotransmitter release. This allows correlation of ionic currents with transmitter release and modulation of release, and analysis of molecular mechanisms of release. b. Using mature frog neuromuscular preparations, we are studying the mechanisms of regulation of transmitter release efficacy by muscle stretch, mediated by integrins. c. Using an old world flying fox bat that has excellent night vision but also has evolved good echolocation, we are attempting to determine whether they can shift seamlessly from one modality to the other. I also have a long-standing interest in the art and iconography of preColumbian ceramics from Central Panama.
Education
B.A., Biology, Harvard University 1958
Ph.D., Biology, Harvard University 1962
Selected Publications
Grinnell AD. (2018) Early milestones in the study of echolocation in bats. J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2018 Jun;204(6):519-536. doi: 10.1007/s00359-018-1263-3. Epub 2018 Apr 23. Review.
Sun XP, Chen BM, Sand O, Kidokoro Y, Grinnell AD. (2010) Depolarization-induced Ca2+ entry evokes release of large quanta in the developing Xenopus neuromuscular junction.J Neurophysiol. 2010 Nov;104(5):2730-40. doi: 10.1152/jn.01041.2009. Epub 2010 Sep 15. PMID: 20844112
Sun XP, Yazejian B, Grinnell AD. (2004) Electrophysiological properties of BK channels in Xenopus motor nerve terminals. J Physiol. 2004 May 15;557(Pt 1):207-28. Epub 2004 Mar 26. PMID: 15047773
Yazejian B, Sun XP, Grinnell AD. (2000) Tracking presynaptic Ca2+ dynamics during neurotransmitter release with Ca2+-activated K+ channels. Nat Neurosci. 2000 Jun;3(6):566-71. PMID: 10816312
Chen BM, Grinnell AD. (1997) Kinetics, Ca2+ dependence and biophysical properties of integrin-mediated mechanical modulation of transmitter release from frog motor nerve terminals. J Neurosci. 1997 Feb 1;17(3):904-16.PMID: 8994045
Barnett Schlinger
Barnett Schlinger
Professor
Associate Dean
Email: schlinge@lifesci.ucla.edu
Office: 2135 TLSB
Phone: (310) 825-5716
Website: http://www.physci.ucla.edu/research/schlinger
Research Interests
Estrogen Synthesis in Brain: We have maintained a long interest in the actions of steroids on the central nervous system developmentally and in adulthood. My lab explores sex steroid synthesis and metabolism with a focus on aromatase the enzyme that catalyzes conversion of androgens into estrogens. Over the years, our work has demonstrated expression and activity of this enzyme in brain of diverse species and with diverse functions. Our work has documented evidence for a role of neuroestrogens in neuronal development and proliferation, neural repair and protection, sexual and aggressive behaviors, learning and memory, and auditory processing.
Neurosteroidogenesis: A concept that emerged a number of years ago was that hormonal steroids could be synthesized, de novo, in the brain itself. For such synthesis to occur, enzymes and transporters are required to be expressed and active in brain that start with cholesterol and, by a series of enzyme catalyzed reactions, produce a diversity of functional steroidal end products. Dogma has held that these biochemical processes occur exclusively in vertebrate gonads and adrenals. Whether this process actually occurred in the vertebrate brain and whether these neurosteroids were functional remained somewhat open questions for many years. My lab explores this phenomenon in wild and captive avian models. Our work supports the concept of functional neurosteroidogenesis and extends our appreciation of this process into our thinking of the hormonal control of natural animal behavior.
Physiology of Elaborate Animal Courtship Over 23 years ago, I began work developing an animal model, the golden-collared manakin (Manacus vitellinus) of Panama, as a system for investigating the hormonal, neural and muscular control of a complex vertebrate behavior. This work spans tropical field behavioral ecology with organ level physiology and molecular and cellular biology. Our study of the extraordinary and physically challenging courtship of male Manacus species has revealed unique specializations in skeletal and muscle anatomy as well as that of endocrine, neural and muscle physiology. Sequencing of this manakin genome together with our efforts to promote genomic sequencing of other manakins, makes these birds now a key animal clade for using molecular genetic approaches to understand the evolution and development of complex social systems and behavior.
Education
B.S., Biology, Tufts University
M.S., Biology, Boston University 1983
Ph.D., Biology, Boston University 1988
Selected Publications
Saldanha, C.J., Remage-Healey, L., Schlinger, B.A. 2011. Synaptocrine Signaling: steroid synthesis and action at the synapse. Endocrine Revs. 32:532 – 549
Barske J., Schlinger B.A.,Wikelski M., Fusani L. Female choice for male motor skills. 2011. Proc. Roy. Soc. Lond. B. 278:3523-3528.
Remage-Healey, L., Dong, S.*, Maidment, N., and B.A. Schlinger. 2011. Presynaptic Control of Rapid Estrogen Fluctuations in the Songbird Auditory Forebrain. J. Neurosci. 31:10034 –10038.
Fuxjager, M., K. Longpre, J. Chew*, L. Fusani and B.A. Schlinger. 2013. Peripheral androgen receptors sustain the acrobatics and fine motor skill of elaborate male courtship. Endocrinology 154: 3168-3177.
Barske, J., Fusani L., Wikelski M., Feng N., Santos M., Schlinger B.A. 2013. Energetics of courtship of Golden-collared manakins (Manacus vitellinus). Proc. Roy. Soc. Lond- B. Dec 18;281(1776):20132482. doi
Fuxjager, M.J., J. Eaton*, W.R Lindsay, L.H Salwiczek, M.A Rensel, J. Barske, L.B Day and B.A Schlinger. 2015. Evolutionary patterns of adaptive acrobatics and physical performance predict expression profiles of androgen receptor – but not estrogen receptor – in the forelimb musculature. Funct. Ecol. 29, 1197–1208.
Fuxjager, M.J. #, J-H., Lee#, T-M., Chan, J. H. Bahn, J.G. Chew*, X.Xiao‡, and Barney A. Schlinger‡. 2016. Hormones, Genes, and Athleticism: Effect of Androgens on the Avian Muscular Transcriptome. Mol Endocrinology, 30: 254-71.
Bodony, D.J, Kharon, Aharon, Swenson, G.W., Wikelski, M., Day, L., Fusani, L., Friscia, A and B.A. Schlinger. 2016. Determination of the wingsnap sonation mechanism of the Golden-Collared Manakin (Manacus vitellinus). J. Exp. Biol. 219: 1524-1534.
Kosarussavadi, S., Pennington, Z. and B.A. Schlinger. 2017. Across Sex and Age: Learning and Memory and Patterns of Avian Hippocampal Gene Expression. Behav. Neurosci. 131: 483-491.
Pradhan, D.S., Van Ness, R.*, Chunqi, M., Jalabert, C., Hamden, J.E., Soma, K.K., Ramenofsky, M. and B.A. Schlinger, B.A. 2019. Phenotypic flexibility of glucocorticoid signaling in skeletal muscles of a songbird preparing to migrate. Horm. Behav. 116, 104586.
James G. Tidball
James G. Tidball
Distinguished Professor
Email: jtidball@physci.ucla.edu
Office: 1135 TLSB
Phone: (310) 206-3395
Biography
My interest in biological research was solidified by my undergraduate experience at Duke University in the Department of Zoology, where I was a student research assistant with Professor Steve Wainwright. Through that experience, I became fascinated with the question of how organisms detect and respond to changes in their mechanical environment. I pursued that question as a Ph.D. student in the lab of Professor David Chapman at Dalhousie University in Halifax, Nova Scotia, where I tried to learn how corals detect the direction of water movement. I then returned to Duke University as a post-doctoral fellow, to further study interactions between cells and the mechanical environment, focusing on the molecular structure of myotendinous junctions (MTJs) where forces generated by muscles are transferred to the extracellular matrix.
Shortly after we initiated those studies of the MTJ, the defective gene product that causes the lethal muscle wasting disease called Duchenne muscular dystrophy (DMD) was discovered by Dr. Lou Kunkel and Eric Hoffman. The missing protein in the disease is a membrane-associated, structural protein called dystrophin, forming the basis for the belief that the disease was caused by a mechanical defect in the muscle cell membrane. My lab then discovered that dystrophin was highly-concentrated at MTJs, but we saw that many features of the disease did not support the idea that DMD was primarily caused by a mechanical defect in the cell membrane. That realization set us on a path to identify the primary cause of muscle cell death in DMD, eventually leading to our discovery that an immune response to the mutant muscle cells was the source of most muscle damage in the disease. Since that finding, we have continued to fully-delineate the role of the immune system in muscular dystrophy, and have built on those findings in pre-clinical studies aimed at manipulating the immune response to reduce the pathology of muscular dystrophy.
Research Interests
Research in the Tidball lab is directed toward understanding processes that regulate skeletal muscle wasting and regeneration. Exploring the mechanisms through which the immune system can modulate skeletal muscle wasting, injury, regeneration and growth is a particular focus of the lab. Discoveries in the our lab over the past 25 years have shown that immune cells, especially myeloid cells, play a major role in modulating muscle injury and repair that occur in chronic, muscle wasting diseases and following acute injuries. For example, our findings have shown that macrophages and eosinophils are key effector cells in the pathogenesis of Duchenne muscular dystrophy. Ongoing investigations in the lab are revealing the identity of specific molecules released by myeloid cells that promote muscular dystrophy. However, discoveries in our lab have also shown that regulatory interactions between cytotoxic, M1 macrophages in dystrophic muscle and anti-inflammatory, M2 macrophages are important in regulating the balance between the death of dystrophic muscle and regenerative processes. This work showed that the experimental manipulation of the balance between the functions of M1 and M2 macrophages can affect the severity of muscular dystrophy, suggesting that manipulation of macrophage phenotype in vivo may have potential therapeutic value for the treatment of the disease. We are now building on those findings in an NIH-funded preclinical investigation in which we are testing whether pharmacological manipulations of co-stimulatory signals that macrophages provide to T-lymphocytes can attenuate the pathology of muscular dystrophy.
Other NIH-funded investigations in our lab explore epigenetic mechanisms through which an anti-aging protein called Klotho affects myogenesis and muscle regeneration in neonatal and aging muscle. We are also determining how those Klotho-driven epigenetic regulatory influences affect muscle growth following acute muscle injury or exercise.
Education
B.S., Duke University 1975
Ph.D., Dalhousie University 1981
Selected Publications
Welc, S.S., Flores, I., Wehling-Henricks, M. Ramos, J. Wang, Y. Bertoni, C. and J. G. Tidball., “Targeting a therapeutic LIF transgene to muscle via the immune system ameliorates muscular dystrophy”, Nature Communications, 10 : 1-17 (2019) .
Wang, Y, M. Wehling-Henricks, S.S. Welc, A.L. Fisher, Q. Zuo and J.G. Tidball., “Aging of the immune system causes reductions in muscle stem cell populations, promotes their shift to a fibrogenic phenotype, and modulates sarcopenia”, FASEB J, 33 (1): 1414-1427 (2019) .
Wang, Y., S.S. Welc, M. Wehling-Henricks and J.G. Tidball., “Myeloid cell-derived tumor necrosis factor-alpha promotes sarcopenia and regulates muscle cell fusion with aging muscle fibers”, Aging Cell, 17 : e12828- (2018) .
Tidball, J.G., Welc, S. and Wehling-Henricks, M., “The immunobiology of inherited muscular dystrophies”, Comprehensive Physiology, 8 : 1313-1356 (2018) .
Wehling-Henricks, M, Welc, S., Samengo, G., Rinaldi, C., Lindsey, C., Wang, Y., Lee, J., Kuro-o, M. and J. G. Tidball., “Macrophages escape Klotho gene silencing in the mdx mouse model of Duchenne muscular dystrophy and promote muscle growth and increase satellite cell numbers through a Klotho-mediated pathway”, Human Molecular Genetics, 27 : 14-29 (2018) .
Tidball, J.G., “Regulation of muscle growth and regeneration by the immune system”, Nature Reviews Immunology, 17 : 165-178 (2017) .
Wehling-Henricks, M., Li, Z., Lindsey, C., Wang, Y., Welc, S.S., Ramos, J.N., Khanlou, N., Kuro-O, M., Tidball, J.G., “Klotho gene silencing promotes pathology in the mdx mouse model of Duchenne muscular dystrophy”, Human Molecular Genetics, 1-18 (2016) .
Wang, Y., Wehling-Henricks, M., Samengo, G. and J.G. Tidball, “Increases of M2a macrophages and fibrosis in aging muscle are influenced by bone marrow aging and negatively regulated by muscle-derived nitric oxide”, Aging Cell, 14 : 678-688 (2015) .
Tidball, J.G. and M. Wehling-Henricks, “Shifts in macrophage cytokine production drive muscle fibrosis”, Nature Medicine, 21 : 665-666 (2015) .
Wang Y, Wehling-Henricks M, Samengo G, Tidball JG “Increases of M2a macrophages and fibrosis in aging muscle are influenced by bone marrow aging and negatively regulated by muscle-derived nitric oxide.” Aging Cell, 14 (4): 678-88 (2015).
Art Arnold
Art Arnold
Distinguished Professor
Email: arnold@ucla.edu
Office: 1129 TLSB
Phone: (310) 825-2169
Website: https://arnoldlab.ibp.ucla.edu/
Biography
I graduated from Grinnell College, and received my PhD from Rockefeller University. Since 1976, I have been a professor at UCLA. I was Chair of the Department of Physiological Science (now Integrative Biology & Physiology) at UCLA (2001-2009), and Director of the Laboratory of Neuroendocrinology of the Brain Research Institute (2005-2017). I was inaugural President of the Society of Behavioral Neuroendocrinology (1997-1999), and received the SBN Lehrman Lifetime Achievement Award in 2010. I was founding Editor-in-Chief of Biology of Sex Differences (2010-2018).
Research Interests
The Arnold lab studies biological factors that make males and females different. Many diseases affect the two sexes differently, implying that one sex is protected or harmed by factors in one sex. It is important to identify the mechanisms underlying the sex difference as one strategy to identify factors that are protective. These factors might be targets for novel therapies.
Many sex differences in physiology and disease are caused by sex hormones coming from the testes or ovaries. We have found, however, that some sex differences also are caused by genes on the sex chromosomes that act outside of the gonads. We are interested in constructing a general theory of sex determination and sexual differentiation that applies to any tissue.
We have used several animal models that offer significant advantages for understanding the factors that cause sex bias in physiology. One is the Four Core Genotypes model, in which the type of the gonad of the animal (testes or ovaries) is not related to its complement of sex chromosomes (XX or XY). This model allows comparing mice that have different sex chromosomes but the same type of gonad, to find traits that are influenced by the complement of sex chromosomes.
Education
A.B., Psychology, Grinnell College 1967
Ph.D., Neurobiology and Behavior, The Rockefeller University 1974
Selected Publications
Arnold AP. 2019 Rethinking sex determination of non-gonadal tissues. Current Topics in Developmental Biology 2019; 134:289-315.
Itoh Y, Golden LC, Itoh N, Matsukawa MA, Ren E, Tse V, Arnold AP, Voskuhl RR. 2019 The X-linked histone demethylase Kdm6a in CD4+ T lymphocytes modulates autoimmunity. Journal of Clinical Investigation 130:3852-3863.
Arnold AP, Disteche CM. 2018 Commentary: Sexual inequality in the cancer cell. Cancer Research 78: 5504-5505.
Umar S, Cunningham CM, Itoh Y, Moazeni S, Vaillancourt M, Sarji S, Centala A, Arnold AP, Eghbali M. 2018 The Y chromosome plays a protective role in experimental hypoxic pulmonary hypertension. American Journal of Respiratory and Critical Care Medicine 197(7):952-955.
Mauvais-Jarvis F, Arnold AP, Reue K. 2017 A guide for the design of pre-clinical studies on sex differences in metabolism. Cell Metabolism 25:1216-1230.
Arnold AP. 2017 A general theory of sexual differentiation. Journal of Neuroscience Research 95:291-300. Online 7 November 2016.
Arnold AP, Cassis LA, Eghbali M, Reue K, Sandberg K. 2017 Sex hormones and sex chromosomes cause sex differences in the development of cardiovascular diseases. Artheriosclerosis Thrombosis & Vascular Biology 37:746-756.
Burgoyne PS, Arnold AP 2016 A primer on the use of mouse models for identifying direct sex chromosome effects on non-gonadal tissues that cause sex differences in traits. Biology of Sex Differences 7:68.
Du S., Itoh N, Askarinama S, Hilla H, Arnold AP, Voskuhl RR. 2014 XY sex chromosome complement, compared with XX, in the CNS confers a greater neurodegenerative response to injury. Proceedings of the National Academy of Sciences, USA, 111:2806-2811.
Chen X, McClusky R, Chen J, Beaven SW, Tontonoz P, *Arnold AP, *Reue K (*equal last authors). 2012 The number of X chromosomes causes sex differences in adiposity and metabolism in mice. PLoS Genetics 8(5):e1002709. Epub 2012 May 10
Gene Block
Gene Block
Distinguished Professor
Chancellor
Email: chancellor@ucla.edu
Office: 2147 Murphy Hall
Phone: (310) 825-2151
Website: https://chancellor.ucla.edu/
Education
B.A. Psychology, Stanford University 1970
M.S., Psychology, University of Oregon 1972
Ph.D., Psychology, University of Oregon 1975
Rachelle Crosbie
Rachelle Crosbie
Professor
Department Chair
Email: rcrosbie@physci.ucla.edu
Office: 2121 TLSB
Phone: (310) 794-2103
Website: https://crosbie.ibp.ucla.edu/
Biography
Rachelle was raised in the Big Thicket of southeast Texas and spent her childhood in search of crawdads, water moccasins, and cottonmouths near the bayou. At the age of nine, she moved with her family to Saudi Arabia, where she learned to scuba dive, ride a camel, and survive in the Arabian desert. All of these adventures prepared her for a life in academia. During college, a summer internship at M.D. Anderson Cancer Center in Houston sparked her interest in pursuing a career in research. She completed her Ph.D. graduate thesis with Professor Emil Reisler in the Department of Biochemistry at UCLA. During this time, she developed a love of protein biochemistry and an appreciation of the intricate relationship between the structure and function of contractile proteins that drive movement in skeletal muscle. As a graduate student, she was also passionate about education and received departmental awards for research and teaching. She then pursued postdoctoral research training in the laboratory of Professor and HHMI Investigator Kevin P. Campbell at the University of Iowa Carver College of Medicine, during which time she was supported by the Robert Sampson Postdoctoral Fellowship from the Muscular Dystrophy Association. Her research was focused on Duchenne muscular dystrophy, which is the most common of the rare diseases that affect children. During her postdoctoral research, she discovered a muscle protein that is associated with dystrophin and assigned it the name sarcospan based on its multiple sarcolemma-spanning domains. Her lab is now focused on basic and translational research of muscular dystrophies. She maintains her passion for education and teaching. She is a National Academies Education Scholar and was awarded the UCLA campus-wide Chancellor’s Distinguished Teaching Award, the Coalition Duchenne Lotus Award, the Golden Test Tube Award, and the Life Sciences Award for Teaching Innovation. She developed a fully online course on Duchenne muscular dystrophy that is offered at all University of California campuses and beyond. She leads a NIH T32 training grant program that supports graduate students and postdoctoral fellows in muscle laboratories at UCLA. The results from her first education focused research study were recently published (Choe et al., 2019 CBE Life Sci Edu). The article describes a new coding method to determine the student engagement value of asynchronous online lecture videos. A second manuscript that is in preparation is focused on how students experience online courses. When out of the lab, Professor Crosbie enjoys driving her 1968 corvette on the Pacific Coast Highway.
Research Interests
Loss of appropriate connection between the muscle cell membrane and its surrounding extracellular matrix is a critical initiating event in Duchenne muscular dystrophy (DMD), which is an inherited muscle wasting disorder that affects all skeletal and cardiac muscles. In fact, there are more children with this inherited muscle-wasting disorder than with all combined childhood cancers; yet there is no treatment. Whereas survival rates for childhood cancers have increased from 58% in 1975-1977 to 80% in 1996-2003, survival rates for DMD have remained the same, 0%. Thirty percent of the mutations in the dystrophin gene are spontaneous, which means that DMD will always be present in the population. Professor Crosbie’s research group has developed the use of the myofiber’s own compensatory mechanisms as a strategy to ameliorate dystrophic muscle. Such approaches are advantages in that they have the potential to target all DMD cases, regardless of the specific dystrophin mutation. Her lab has discovered that sarcospan, a transmembrane protein, evokes a set of molecular events that, when individually activated in DMD muscle, ameliorate dystrophin-deficient disease including cardiac, respiratory, and skeletal muscle dysfunction. The Crosbie lab has identified new chemical entities (small compounds) that activate sarcospan in DMD muscle cells, which the lab is pursuing as a treatment for DMD. Professor Crosbie’s group has also developed an in vitro platform to investigate the interaction of muscle resident cells with the extracellular matrix as a mechanism to investigate the effect of fibrosis on muscle function in health and disease. Professor Crosbie’s research has been continuously funded by NIH R01 grants, in addition to grants from industry and non-profit organizations.
Education
B.S., Biochemistry, Texas A&M University 1989
Ph.D., Biochemistry, University of California, Los Angeles 1994
Postdoctoral Fellowship, University of Iowa Carver College of Medicine
Selected Publications
Shu C, Kaxon-Rupp AN, Collado JR, Damoiseaux R, Crosbie RH (2019) ‘Development of a high-throughput screen to identify small molecule enhancers of sarcospan for the treatment of Duchenne muscular dystrophy.’ Skelet Muscle, 9 (1): 32. PMID: 31831063.
Choe RC, Scuric Z, Eshkol E, Cruser S, Arndt A, Cox R, Toma SP, Shapiro C, Levis-Fitzgerald M, Barnes G, Crosbie RH (2019) ‘Student Satisfaction and Learning Outcomes in Asynchronous Online Lecture Videos.’ CBE Life Sci Educ, 18 (4): ar55. PMID: 31675279.
Gibbs EM, Barthélémy F, Douine ED, Hardiman NC, Shieh PB, Khanlou N, Crosbie RH, Nelson SF, Miceli MC (2019) ‘Large in-frame 5′ deletions in DMD associated with mild Duchenne muscular dystrophy: Two case reports and a review of the literature.’ Neuromuscul Disord, 29 (11): 863-873. PMID: 31672265.
Parvatiyar MS, Brownstein AJ, Kanashiro-Takeuchi RM, Collado JR, Dieseldorff Jones KM, Gopal J, Hammond KG, Marshall JL, Ferrel A, Beedle AM, Chamberlain JS, Renato Pinto J, Crosbie RH (2019) ‘Stabilization of the cardiac sarcolemma by sarcospan rescues DMD-associated cardiomyopathy.’ JCI Insight, 4 (11): 1-21. PMID: 31039133.