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
Peter Narins
Research Interests
My research focuses on the question of how animals extract relevant sounds from the often highly noisy backgrounds in which they live. The techniques I use are the quantitative analysis of vocal behavior of animals in their natural habitats, followed by single fiber neurophysiological recordings in order to elucidate mechanisms underlying signal processing in noise. A second research direction is based on the discovery of the remarkable sensitivity to substrate vibrations possessed by burrowing animals. We are now characterizing and providing accurate measurements of vibrational thresholds as well as exploring the differences between substrate-vibration and airborne sound at the cellular level. Other projects carried out by our group have included an investigation of the neurophysiological basis of sound localization in noisy environments, a study of the temperature-dependence of the representation of time in the vertebrate auditory system, the biophysics of sound localization and the evolution of the middle ear reflex in vertebrates. Current projects include using laser Doppler vibrometry to elucidate the sound pathways relevant for stimulation of both the middle and inner ear in small vertebrates, and using whole-cell voltage clamp techniques to carry out an anatomical and physiological study of the mechanisms underlying transduction in vertebrate sensory hair cells. In addition, we supplement the lab work with direct behavioral observations and controlled acoustic playback studies carried out with animals in their natural habitats. These have included both Old and New World lowland wet tropical forests, African deserts and temperate forests in South America.
Education
B.S., Electrical Engineering, Cornell University 1965
M.S., Electrical Engineering, Cornell University 1966
Ph.D., Neurobiology and Behavior, Cornell University 1976
Selected Publications
Narins, P.M. and Meenderink, S.W.F., “Climate change and frog calls: Long-term correlations along a tropical altitudinal gradient”, Proc. Roy. Soc. Lond, 281 : 1-6 (2014) .
Narins, P.M., Wilson, M. and Mann, D., “Ultrasound detection in fishes and frogs: Discovery and mechanisms”, In: Insights from Comparative Hearing Research, C. Koeppl, G.A. Manley, A.N. Popper, R.R. Fay(Eds.), 133-156 (2014) .
Adler, K., Narins, P.M. and Ryan, M.J., “Obituary. Robert R. Capranica (1931-2012) and the Science of Anuran Communication”, Herpetological Review, 44 : 554-556 (2013) .
Miller, M.E., Nasiri, A.K., Farhangi, P.O., Farahbakhsh, N.A., Lopez, I.A., Narins, P.M. and Simmons, D.D., “Evidence for water-permeable channels in auditory hair cells in the leopard frog”, Hear. Res, 292 : 64-70 (2012) .
Manley, G.A., Narins, P.M. and Fay, R.R,, “Experiments in comparative hearing: Georg von Bekesy and beyond”, Hear. Res, 293 : 44-50 (2012) .
Cui, J., Tang, Y. and Narins, P.M., “Real estate ads in Emei music frog vocalizations: Female preference for calls emanating from burrows”, Biol. Letters, 8 : 337-340 (2012) .
Chen. H.-H. A. and Narins, P.M., “Wind turbines and ghost stories: The effects of infrasound on the human auditory system”, Acoustics Today, 8 : 51-56 (2012) .
Quinones, P.M., Luu, C., Schweizer, F.E. and Narins, P.M., “Exocytosis in the frog amphibian papilla”, J. Asso. Res. Otolaryngol, 13 : 39-54 (2012) .
Arch, V.S., Simmons, D.D., Quinones, P.M., Feng, A.S., Jiang, J., Stuart, B., Shen, J.-X., Blair, C. and Narins, P.M., “Inner ear morphological correlates of ultrasonic hearing in frogs”, Hear. Res, 283 : 70-79 (2012) .
Shen, J.-X., Xu. Z.-M., Feng, A. and Narins, P.M., “Large odorous frogs (Odorrana graminea) produce ultrasonic calls”, J. Comp. Physiol, 197 : 1027-1030 (2011) .
Gina Poe
Gina Poe
Professor
Director of Maximizing Access to Research Careers U*STAR Program
Eleanor Leslie Chair in Innovative Brain Research
Email: ginapoe@ucla.edu
Office: 1032 TLSB
Phone: (310) 825-8939
Website: poe_sleeplab@weebly.com
Biography
Gina Poe has been working since 1995 on the mechanisms through which sleep serves memory consolidation and restructuring. Dr. Poe is a southern California native who graduated from Stanford University then worked for two post-baccalaureate years at the VA researching Air Force Test Pilots’ brainwave signatures under high-G maneuvers. She then earned her PhD in Basic Sleep in the Neuroscience Interdepartmental Program at UCLA under the guidance of Ronald Harper then moved to the University of Arizona for her postdoctoral studies with Carol Barnes and Bruce McNaughtons looking at graceful degradation of hippocampal function in aged rats as well as hippocampal coding in a 3-D maze navigated in the 1998 space shuttle mission. She brought these multiunit teachings to answer a burning question of whether REM sleep were for remembering or forgetting and found that activity of neurons during REM sleep is consistent both with the consolidation of novel memories and the elimination of already consolidated memories from the hippocampus, readying the associative memory network for new learning the next day. Moving first to Washington State University then to the University of Michigan before joining UCLA in 2016, Poe has over 80 undergraduates, 6 graduate students, and 6 postdoctoral scholars, and has served in university faculty governance as well as leading 5 different programs designed to diversify the neuroscience workforce and increase representation of people of the global majority in the STEM fields. At UCLA she continues research and teaching and Directs the COMPASS-Life Sciences and BRI-SURE programs and co-Directs the MARC-U*STAR program. Nationally she is course director of the Marine Biological Lab’s SPINES course and co-Directs the Society for Neuroscience’s NSP program which earned the nation’s highest mentoring honor in 2018. These programs have served over 600 PhD level trainees over the years.
Research Interests
The Poe lab investigates the mechanisms by which sleep traits serve learning and memory consolidation. Memories are encoded by the pattern of synaptic connections between neurons. We employ tetrode recording and optogenetic techniques in learning animals to see how neural patterns underlying learning are reactivated during sleep, and how activity during sleep influences the neural memory code. Both strengthening and weakening of synapses is important to the process of sculpting a network when we make new memories and integrate them into old schema. Results from our studies suggest that while synaptic strengthening can be efficiently accomplished during the waking learning process, the synaptic weakening part of memory integration requires conditions unique to sleep. The absence of noradrenaline during sleep spindles and REM sleep as well as the low levels of serotonin during REM sleep allow the brain to integrate new memories and to refresh and renew old synapses so that we are ready to build new associations the next waking period. Memory difficulties involved in post-traumatic stress disorder, Schizophrenia, Alzheimer’s disease and even autism involve abnormalities in the sleep-dependent memory consolidation process that my lab studies. Keywords: Sleep, learning and memory, PTSD, memory consolidation, reconsolidation, REM sleep, sleep spindles, Norepinephrine, LTP, depotentiation, reversal learning, optogenetics, electrophysiology, tetrode recordings, hippocampus, prefrontal cortex.
Education
B.A., Human Biology, Stanford University 1987
Ph.D., Neuroscience, University of California, Los Angeles 1995
Selected Publications
Cabrera Y, Holloway J, Poe GR (2020) ‘Sleep Changes Across the Female Hormonal Cycle Affecting Memory: Implications for Resilient Adaptation to Traumatic Experiences.’ J Womens Health (Larchmt), 29 (3): 446-451. PMID: 32186966
Swift KM, Keus K, Echeverria CG, Cabrera Y, Jimenez J, Holloway J, Clawson BC, Poe GR () ‘Sex differences within sleep in gonadally-intact rats.’ Sleep, 2019.PMID: 31784755
Swift KM, Gross BA, Frazer MA, Bauer DS, Clark KJD, Vazey EM, Aston-Jones G, Li Y, Pickering AE, Sara SJ, Poe GR (2018) ‘Abnormal Locus Coeruleus Sleep Activity Alters Sleep Signatures of Memory Consolidation and Impairs Place Cell Stability and Spatial Memory.’ Curr Biol, 28 (22): 3599-3609.e4. PMID: 30393040
Zaborszky L, Gombkoto P, Varsanyi P, Poe GR, Role L, Ananth M, Rajebhosale P, Talmage D, Hasselmo M, Dannenberg H, Minces V, Chiba A, “Specific basal forebrain-cortical cholinergic circuits coordinate cognitive operations”, J Neurosci, 38 (44): 9446-9458 (2018).
Lewis P, Knoblich G, Poe GR, “Recasting reality: how memory replay in sleep boosts creative problem solving”, Trends Cogni Sci, 22 (6): 491-503 (2018).
Bjorness TE, Booth V, Poe GR (2018) ‘Hippocampal theta power pressure builds over non-REM sleep and dissipates within REM sleep episodes.’ Arch Ital Biol, 156 (3): 112-126. PMID: 30324607
Poe GR (2017) ‘Sleep Is for Forgetting.’ J Neurosci, 37 (3): 464-473. PMID: 28100731
Javanbakht, A and Poe, GR, “Behavioral neuroscience of circuits involved in arousal regulation”, The Neurobiology of PTSD, Ressler, K and Liberzon, I(Eds.), 130-147 (2016).
Emrick JJ, Gross BA, Riley BT, Poe GR (2016) ‘Different Simultaneous Sleep States in the Hippocampus and Neocortex.’ Sleep, 39 (12): 2201-2209. PMID: 27748240
Vanderheyden WM, George SA, Urpa L, Kehoe M, Liberzon I, Poe GR (2015) ‘Sleep alterations following exposure to stress predict fear-associated memory impairments in a rodent model of PTSD.’ Exp Brain Res, 233 (8): 2335-46. PMID: 26019008.
Watts A, Gritton HJ, Sweigart J, Poe GR (2012) ‘Antidepressant suppression of non-REM sleep spindles and REM sleep impairs hippocampus-dependent learning while augmenting striatum-dependent learning.’ J Neurosci, 32 (39): 13411-20. PMID: 23015432
Booth V, Poe GR (2006) ‘Input source and strength influences overall firing phase of model hippocampal CA1 pyramidal cells during theta: relevance to REM sleep reactivation and memory consolidation.’ Hippocampus, 16 (2): 161-73. PMID: 16411243
Amy Rowat
Amy Rowat
Professor
Vice Chair of Master’s Program
Marcie H. Rothman Presidential Chair in Food Studies
Email: rowat@ucla.edu
Office: 1125 TLSB
Phone: (310) 825-4026
Website: http://www.physci.ucla.edu/research/rowat/RowatLab.html
Biography
Amy Rowat is a biophysicist with degrees from Mount Allison University (B.Sc. Honors Physics; B.A. Asian Studies, French, & Math), the Technical University of Denmark (M.Sc. Chemistry), and the University of Southern Denmark (Ph.D. Physics). She completed postdoctoral training at Harvard University and Brigham-Women’s Hospital, and was a Research Fellow at the German Cancer Research Center (DKFZ). Rowat is Associate Professor and Vice Chair of Graduate Education in the Department of Integrative Biology & Physiology at the University of California at Los Angeles. She is also a member of the UCLA Bioengineering Department, the Center for Biological Physics, the Jonsson Comprehensive Cancer Center, and the Broad Stem Cell Research Center. Rowat is the author of over 50 scientific papers and inventor on over 6 patents. She is the recipient of numerous awards for excellence in research innovation and teaching, including the prestigious National Science Foundation CAREER award. Rowat has pioneered the use of food to teach sophisticated concepts in science, and has both written and lectured on the topic of science and food to hundreds of UCLA students and public audiences. Rowat is also Founder and Director of the Science&Food non-profit organization and leads the Food Pod of the Semel Healthy Campus Initiative Center at UCLA.
Research Interests
Biology is commonly described in terms of specific genes and chemical reactions – transcription, translation – and cells as sacs filled with DNA. But cells are materials and the physical properties of cells are critical for many physiological functions: how cells deform to circulate through the body; how cells resist mechanical stresses – like stretching or squeezing – is important for homeostasis, and also critical in many diseases where cells have altered physical properties.
In the Rowat lab we think about how tissues and cells sense and respond to external cues in terms of cells as materials: how do cells maintain their physical properties and regulate them in response to external cues?
To address this question we have three main research goals:
1) MEASURE: We are developing new mechanotyping technologies, such as self-assembling scaffolds that have tunable mechanics and topology as well as a deformability screening platform – we recently tested thousands of small molecules and found compounds that make cancer cells stiffer and less invasive; this also enables us to develop systems-level knowledge of the ‘mechanome’.
2) UNDERSTAND: Measuring physical properties are not enough. We are defining the molecules and pathways that regulate cellular mechanotype. For example, we discovered that soluble stress hormones activate a pathway that causes cancer cells to increases the forces they use to pull on their surrounding matrix, which makes them invade more quickly. Knowing that molecules are involved is an important first step towards intervening to stop cancer cells from spreading.
3) TRANSLATE: We are harnessing mechanobiology for translation to applications from cancer to cellular agriculture. In addition to molecules we have identified to stop cancer cell invasion, we are also applying our knowledge to tumors as 3D materials. For example, modulating cellular force generation can change tumor porosity, and ultimately increase the accessibility to chemotherapy drugs. While cancer is a main focus of our work, our approaches can be broadly applied across cell types, and we have also investigated cell physical properties in the context of immune cells to cardiac regeneration to neurological movement disorders such as dystonia to cultured meat.
To achieve these research goals, our multidisciplinary team consists of researchers with backgrounds in cell biology, physics, engineering, cancer progression, systems biology, and chemistry.
Education
B.Sc., Physics, Mount Allison University 1998
B.A., Asian Studies, French, & Math, Mount Allison University 1999
M.Sc., Chemistry, Technical University of Denmark 2001
Ph.D., Physics, University of Southern Denmark 2005
Selected Publications
Kim TH, Ly C, Christodoulides A, Nowell CJ, Gunning PW, Sloan EK♯, Rowat AC♯., “Stress hormone signaling through β-adrenergic receptors regulates macrophage mechanotype and function”, FASEB Journal, (2019) .
Gill NK, Ly C, Nyberg KD, Lee L, Qi D, Tofig B, Reis-Sobreiro M, Dorigo O, Rao J, Wiedemeyer R, Karlan B, Lawrenson K, Freeman MR, Damoiseaux R, Rowat AC (2019) ‘A scalable filtration method for high throughput screening based on cell deformability.’ Lab Chip, 19 (2): 343-357. PMID: 30566156
Sobreiro MR, Chen JF, Novitskya T, You S, Morley S, Steadman K, Gill NK, Eskaros A, Rotinen M, Chu CY, Chung LWK, Tanaka H, Yang W, Knudsen BS, Tseng HR, Rowat AC, Posadas EM, Zijlstra A, Di Vizio D, Freeman MR, “Emerin deregulation links nuclear shape instability to metastatic potential”, Cancer Research, 78 (21): 6086-6097 (2018) [link].
Nyberg KD, Bruce SL, Nguyen AV, Chan CK, Gill NK, Kim TH, Sloan EK, Rowat AC, “Predicting cancer cell invasion by single-cell physical phenotyping”, Integrative Biology, 10 : 218-231 (2018) .
Kim TH, Gill NK, Nyberg KD, Nguyen AV, Hohlbauch SV, Geisse NA, Nowell CJ, Sloan EK, Rowat AC (2016) ‘Cancer cells become less deformable and more invasive with activation of β-adrenergic signaling.’ J Cell Sci, 129 (24): 4563-4575. PMID: 27875276
Kim TH, Rowat AC*, Sloan E*, “Neural regulation of cancer: from mechanobiology to inflammation”, Clinical and Translational Immunology, 5 : e78- (2016) .
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.
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
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).
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
Scott Chandler
Biography
I am married to my lovely wife Sonja for 35 years and have two wonderful daughters, Jennifer and Danielle. We love to travel, hike and photograph our journeys. I have a passion for photography and specialize in both landscape and sports genres. I regularly photograph sports events for the UCLA athletic department and have a number of prints on the Walls of UCLA buildings, such as Powell library and the Geology building.
Research Interests
My global interest is in how the central nervous system controls movement. Precisely how we produce coordinated, rhythmical movements such as locomotion, mastication, and respiration is a fundamental problem in neuroscience that is poorly understood. During injury or disease these basic types of movements, which we take for granted, can be compromised. My lab uses animal models to study how rhythmical jaw movements are produced. We use a combination of electrophysiological, molecular, pharmacological techniques in conjunction with computational modeling and bioinformatics to address basic questions about how single and small networks of neurons in the brainstem orchestrate coordinated activity in synapses and ion channels to produce unique discharge patterns that occur during rhythmical movements. We have found that localized groups of neurons within small areas of the brainstem are important for the basic rhythmic component of mastication and that specific ion channels are activated to produce the appropriate discharge patterns reminiscent of masticatory patterns. More recently, the lab has obtained transgenic mice that produce the majority of symptoms of the devastating disease, Amyotrophic Lateral Sclerosis (ALS), otherwise known as Lou Gehrig’s disease. We found that certain ion channels in both sensory and motor neurons are abnormally active prior to the onset of symptoms of the disease. Although these studies are in the early stages, they could provide insight into how the motoneuronal neurodegeneration that is responsible for paralysis and death occur, and will start to identify new molecular targets for development of rational drug therapies to delay motoneuronal degeneration and prolong the life of ALS patients.
Education
B.S., Neurobiology, University of California, Berkeley
Ph.D., Physiology/Neurophysiology, University of California, Los Angeles 1979
Selected Publications
Liu W, Venugopal S, Majid S, Ahn IS, Diamante G, Hong J, Yang X, Chandler SH (2020) ‘Single-cell RNA-seq analysis of the brainstem of mutant SOD1 mice reveals perturbed cell types and pathways of amyotrophic lateral sclerosis.’ Neurobiol Dis, In Press. PMID: 32360664
Seki S, Tanaka S, Yamada S, Tsuji T, Enomoto A, Ono Y, Chandler SH, Kogo M (2020) ‘Neuropeptide Y modulates membrane excitability in neonatal rat mesencephalic V neurons.’ J Neurosci Res, 98 (5): 921-935. PMID: 31957053
Venugopal S, Seki S, Terman DH, Pantazis A, Olcese R, Wiedau-Pazos M, Chandler SH (2019) ‘Resurgent Na+ Current Offers Noise Modulation in Bursting Neurons.’ PLoS Comput Biol, 15 (6): e1007154. PMID: 31226124
Salomon D., Martin-Harris., Mullen B., Odegaard B., ZvinyatskovskiyA., and Chandler S.H, “Brain Literate: Making Neuroscience Accessible to a Wider Audience of Undergraduates”, J. Undergraduate Neurosci. Educ, 13 : 1-9 (2015) .
Masoumi A., Low E., Shoghi T., Chan P., Hsiao CF., Chandler S.H., & Martina Wiedau-Pazos., “Enrichment of human embryonic stem cell derived motor neuron cultures using arabinofuranosyl cytidine”, Future Neurol, 10 : 91-99 (2015) .
Venugopal S., Hsiao CF., Sonoda T., Weidau-Pazos M.,and Chandler S.H., “Homeostatic dysregulation in membrane properties of masticatory motoneurons compared to oculomotor neurons in a mouse model for Amyotrophic Lateral Sclerosis”, J. Neurosci, 35 : 707-720-720 (2015) .
Tsuruyama K, Hsiao CF, Chandler SH, “Participation of a persistent sodium current and calcium-activated nonspecific cationic current to burst generation in trigeminal principal sensory neurons”, J. Neurophysiology, 110 : 1903-1914 (2013) .
Hsiao CF, Kaur G, Vong A, Bawa H, Chandler SH, ” Participation of Kv1 channels in control of membrane excitability and burst generation in mesencephalic V neurons”, J. Neurophysiology, 101 : 1407-1418 (2009) .
Hsiao, C.F., Gougar, K., Asai, J. and Chandler, S.H, ” Intrinsic membrane properties and morphological characteristics of interneurons in the rat supratrigeminal region”, J.Neurosci. Res, 85 : 3673-3686 (2007) .
Enomoto, A., Han, J.M., Hsiao, C.F., Wu, N. and Chandler, S.H., “Participation of sodium currents in burst generation and control of membrane excitability in mesencephalic trigeminal neurons”, J Neurosci, 26 : 3412-3422 (2006) .
612 Charles E. Young Drive East
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