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Integrative Biology and Physiology

Professors

Stephanie White

Stephanie White

Professor
Director of Undergraduate Neuroscience Interdepartmental Program (UNSIDP)
William Scheibel Endowed Chair in Neuroscience

Stephanie White

Email: sawhite@ucla.edu
Office: 1028 TLSB
Phone: (310) 794-1888
Website: http://www.physci.ucla.edu/research/white

Research Interests

Our capacity for language is near or at the essence of what makes us human. How this trait evolved is puzzling given that non-human primates can’t learn their vocalizations. (In the wild, adult chimps sound much like baby chimps but with deeper voices.) Precursor Homo groups speaking precursors to language no longer exist. My research group focuses on one aspect of language: the ability of youngsters to listen to and compare their own vocalizations to those of adults and thereby move from babbling to pronouncing interpretable sounds. For this we study songbirds and ask how the puzzle pieces of their brains fit together to accomplish vocal mimicry. We currently focus on a molecule known as FoxP2 that, when disrupted in humans or birds, disrupts speech or song, respectively. FoxP2 connects to the network of molecules that together enable learned vocal communication. We are investigating the functional role of FoxP2 in song and at synapses in the underlying control circuitry. We are also investigating the network of molecules downstream of FOXP2 and their role in disorders of speech including in autism.

Education

B.S., Biopsychology, Connecticut College
Ph.D., Neuroscience, Stanford University

Selected Publications

Fraley ER, Burkett ZD, Day NF, Schwartz BA, Phelps PE & White SA, “Mice with Dab1 or Vldlr insufficiency exhibit abnormal neonatal vocalization patterns”, Scientific Reports, 6 : 25807- (2016) .

Berg JM, Lee C, Chen L, Galvan L, Cepeda C, Chen JY, Penagarkano O, Stein JL, Li A, Oguro-Ando A, Miller JA, Vahisht AA, Starks ME, Kite EP, Al-Sharif NB, Burkett ZD, White SA, Fears SC, Levine MS, Wohlschlegel JA & Geschwind DG, “JAKMIP1 links regulation of neuronal protein translation to autism”, Neuron, 88 : 1173-1191 (2015) .

*Miller JE, *Hafzalla G, Burkett ZD, Fox CM & White SA, “Dopamine depletion in basal ganglia song nucleus reduces vocal variability in adult male zebra finches”, Physiological Reports, 3 : e12599- (2015) .

Hara E, Perez J, Whitney O, Chen Q, White SA & Wright T, “Neural FoxP2 and FoxP1 expression in the budgerigar, an avian species with adult vocal learning”, Behavioral Brain Research, 283 : 22-29 (2015) .

Heston JB & White SA, “Behavior-linked FoxP2 regulation enables zebra finch vocal learning”, Journal of Neuroscience, 35 : 2885-2894 (2015) .

Whitney O, Voyles T, Hara E, Chen Q, White SA & Wright T, “Differential FoxP2 and FoxP1 expression in a vocal learning nucleus of the developing budgerigar”, Developmental Neurobiology, 75 : 778-790 (2015) .

Hilliard AT*, Miller JE*, Fraley ER, Horvath S & White SA, “Molecular microcircuitry underlies the functional specification of a basal ganglia circuit dedicated to vocal learning”, Neuron, 73 : 537-552 (2012) .

White, S.A., “Genes and vocal learning”, Brain and Language, 115 : 21-28 (2011) .

Panaitof, S.C., Abrahams, B.S., Dong, H., Geschwind, D.H. and White, S.A., “Language-related Cntnap2 gene is differentially expressed in sexually dimorphic nuclei essential for vocal learning in songbirds”, Journal of Comparative Neurology, 5 : 1995-2018 (2010) .

Miller, J.E., Hilliard, A.T. and White, S.A., “Song practice promotes acute vocal variability during sensorimotor learning”, PLoS ONE, 5 : e8592- (2010) .

 

Roy Wollman

Roy Wollman

Professor

Roy Wollman

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) .

Mark Frye

Mark Frye

Professor
Director of Molecular, Cellular and Integrative Physiology (MCIP) Interdepartmental Ph.D. Program

Email: frye@ucla.edu
Office: 2014 TLSB
Phone: (310) 825-5360
Website: https://sites.lifesci.ucla.edu/ibp-frye/

Biography

Professor Frye grew up in upstate New York, and after completing a BA in psychology at SUNY Oneonta, he expanded his studies of neuroscience at Union College, where he received his MS for research on the cellular neurophysiology of dragonfly vision with Robert Olberg. He moved to University of Washington to complete a PhD on the sensory biomechanics of flight control in the hawkmoth under the mentorship of Tom Daniel and Jim Truman. His postdoctoral training was with Michael Dickinson at UC Berkeley and Caltech studying multimodal sensory control of flight behavior in Drosophila. In his own lab he uses virtual reality behavior, neurogenetics, and live brain imaging to understand how sensory signals are encoded, fused across modalities, and transformed into the motor control of complex behavior.

Research Interests

General introduction How are flexible and robust animal behaviors orchestrated by the nervous system? Different forms of this general question have occupied neuroscientists for decades. Great strides have been made toward describing the elements of nervous system development, structure, and function. Our next challenge is to examine how behavior emerges from the interactions among genetic, cellular, cell-system, and organ-system levels of organization. My laboratory studies these interactions in a powerful model system ? the fruit fly Drosophila melanogaster. Whereas research with Drosophila is most often focused within the molecular-genetic spectrum of modern biology, this animal also shows remarkable behavioral performance, making its living navigating vast distances through complex visual landscapes in search of the source of an attractive odor. A fly?s sophisticated navigation capabilities emerge from the fusion of multiple sensory modalities and transformation of a robust motor code. By combining the rapidly expanding toolkit of fruit fly molecular genetics with live imaging and ‘virtual reality’ behavioral techniques, we hope to reveal the functional mechanisms and structural circuits with which the fly brain coordinates the biomechanics and dynamics of complex sensory behavior. The results of this cross-disciplinary approach could have broad impact on our understanding of the general principles of sensory fusion and sensory-motor integration common among animal taxa, and also motivate specialized technical advances in bio-inspired robotic devices.

Education

M.S., Neuroscience, Union College 1992
Ph.D., Zoology, University of Washington 2000

Selected Publications

Keleş MF, Hardcastle BJ, Städele C, Xiao Q, Frye MA. Inhibitory Interactions

and Columnar Inputs to an Object Motion Detector in Drosophila. Cell Reports, (7):2115-2124 (2020).

Cheng KY, Frye MA. Neuromodulation of insect motion vision. Journal of Comparative Physiology A. 206(2):125-137 (2020).

Mongeau JM, Frye MA, “Flies spatio-temporally integrate visual signals to control saccades”, Current Biology, 27 (9): 2901-2914 (2017) .

Aptekar JW, Keles MF, Lu PM, Zolotova NM, Frye MA, “Neurons forming optic glomeruli compute figure-ground discriminations”, J Neuroscience, 35 : 7587-7599 (2015) .

Frye MA, “Quick guide: Elementary motion detectors”, Curr Biol, 25 : R215-217 (2015) .

Wasserman SW, Aptekar JW, Lu PM, Nguyen J, Wang AL, Keles MF, Grygoruk A, Krantz DE, Larsen C, Frye MA, “Olfactory neuromodulation of motion vision circuitry in Drosophila”, Curr Biol, 25 : 467-472 (2015) .

 

David Glanzman

David Glanzman

Distinguished Professor

Email: glanzman@ucla.edu
Office: 2357C Gonda (Goldschmied) Center
Phone: (310) 206-9972

Biography

I began my academic career as an English and film major at Oberlin College. After two years of college, I decided to explore the world, and spent a year-and-a-half living in New York City’s East Village, working as a silkscreen printer and apprentice film editor. My curiosity about the world somewhat satisfied, I decided to return to college; I eventually graduated from Indiana University with a B.A. in psychology. I then obtained a Ph.D. in experimental psychology from Stanford University, and afterwards did postdoctoral stints in the laboratories of Frank Krasne at UCLA and Eric Kandel at the Howard Hughes Medical Institute at Columbia University. It was in Kandel’s laboratory that I began my work on learning and memory in Aplysia (see below). In 1990 I was hired as an Assistant Professor in the Department of Integrative Biology & Physiology (formerly Physiological Science), where I am now a Professor. In addition, I am also a Professor in the Department of Neurobiology in the David Geffen School of Medicine.

Research Interests

My laboratory is interested in the cell biology of learning and memory in simple organisms. In our research we use two animals, the marine snail Aplysia californica, and the zebrafish (Danio rerio).
Work on Aplysia: This invertebrate has a comparatively simple nervous system (~ 20,000 neurons) that provides a valuable experimental model for understanding the cellular mechanisms that underlie simple forms of learning, such as habituation, sensitization, and classical conditioning. Another experimental advantage of Aplysia is that sensory and motor neurons that mediate specific reflexes of the animal can be placed into dissociated cell culture where they will reform their synaptic connections. These in vitro sensorimotor synapses are extremely useful for cellular and molecular studies of short- and long-term learning-related synaptic plasticity. Currently, my laboratory is investigating the mechanisms that underlie the persistence of memory: How are memories maintained in our brains over long periods of time? Recently, we have found evidence that RNA-induced nuclear changes, particularly epigenetic changes, play a critical role in memory storage. Specifically, we have found that a long-term memory can be reinstated after manipulations that erase the behavioral and synaptic memory expressions of the memory; by contrast, the memory cannot be reinstated after its disruption by inhibition of an epigenetic process, DNA methylation. We have also found that long-term memory can be transferred from trained to naive, untrained snails if RNA extracted from the nervous systems of sensitization-trained snails is injected into untrained snails. By contrast, RNA from untrained donor snails does not induce sensitization when injected into untrained recipients. These results challenge the synaptic plasticity model of memory.
Work on the zebrafish: The zebrafish has significant advantages for genetic and molecular studies of behavior, including studies of learning and memory. The zebrafish is amenable to both forwards and reverse genetics. Furthermore, although it is a vertebrate with a complex vertebrate nervous system, it possesses reflexive behaviors that are mediated by relatively simple neural circuits in the spinal cord and brainstem. Finally, zebrafish larvae are transparent, which facilitates the use of optogenetics and advanced imaging techniques to study learning-related neural activity within the intact animal. We study the neural basis of nonassociative learning and memory in zebrafish larvae. In addition, we are investigating olfactory-based associative learning in these organisms.

Education

B.A., Psychology, Indiana University Bloomington 1973
Ph.D., Psychology, Stanford University 1980

Selected Publications

Abraham WC, Jones OD, Glanzman DL (2019) ‘Is plasticity of synapses the mechanism of long-term memory storage?’ NPJ Sci Learn, 4 (): 9. PMID: 31285847

Bedecarrats, A. Chen, S. Pearce, K. Cai, D. Glanzman, D. L., “RNA from trained Aplysia can induce an epigenetic engram for long-term sensitization in untrained Aplysia”, eNeuro, 5 (3): (2018)

Pearce, K. Cai, D. Roberts, A. C. Glanzman, D. L., “Role of protein synthesis and DNA methylation in the consolidation and maintenance of long-term memory in Aplysia”, eLife, 6 : (2017)

Chen, S., Cai, D., Pearce, K., Sun, P.Y., Roberts, A.C., Glanzman, D.L.,, “Reinstatement of long-term memory following erasure of its behavioral and synaptic expression in Aplysia”, eLife, (2014)

Roberts, A.C., Bill, B.R., and Glanzman, D.L., “Learning and memory in zebrafish larvae”, Front. Neural Circuits, (2013)

Crystal, J.D., and Glanzman, D.L., “A biological perspective on memory”, Current Biology, 23 (17): R728-R731 (2013)

 

Press and Media

Interesting discussion of our recent eLife paper in Discover: http://blogs.discovermagazine.com/neuroskeptic/2014/12/27/synapse-memory-doctrine-threatened/#.VNAEAUKBujA

Another article about our eLife paper in Scientific American: http://www.nature.com/scientificamerican/journal/v312/n4/pdf/scientificamerican0415-14.pdf

Article on my research in The Huffington Post: http://www.huffingtonpost.com/2014/12/23/neuroscience-memory-_n_6366588.html

TEDx talk on long-term memory: https://www.youtube.com/watch?v=mLp6PUPqscs

NSN Short A Memorable Snail NOVA Vodcast published 08-21-2009 13:00:00

Video interview on learning and consciousness (scroll down for David Glanzman video)

Audio interview in The DNA Files show “Minding the Brain”

Interview in the online news source “The Mark” (May 19, 2011): http://www.themarknews.com/articles/5222-eternal-sunshine-is-just-around-the-corner?page=1

Article on my research in the May 10, 2011, issue of “The Atlantic”: http://www.theatlantic.com/life/archive/2011/05/even-if-we-could-erase-bad-memories-should-we/238444/

Fernando Gomez-Pinilla

Fernando Gomez-Pinilla

Professor in Residence

Email: fgomezpi@ucla.edu
Office: 1814 LS
Phone: (310) 206-9693
Website: http://www.physci.ucla.edu/research/GomezPinilla/

Research Interests

Role of Trophic Factors on Activity-dependent Plasticity We are interested on the mechanisms by which environmental factors affect neuronal health. We have found that trophic factors endogenous to the brain and spinal cord can be induced by the practice of select behaviors. We have recently reported that physical activity, learning, and nutritional factors control neurotrophins in the brain. These findings opened the exciting possibility that regulation of trophic factors by behavior can be a pivotal mechanism by which specific experiences can impact the structure and function of the CNS. It may account for the improvement of CNS function after trauma provided by rehabilitative therapies. On the contrary, it may explain the decay in function in aging or degenerative diseases following a lack of stimulation. These two avenues provide direction for my research program: 1) How trophic factors induced by activity can help functional recovery following brain and spinal cord trauma. We are using several exercise models to boost the production of trophic factors in the brain and spinal cord. Our goal is to provide critical information to guide the design of behavioral therapies for the reduction of the severity of insult or disease, and to increase CNS function. 2) We are evaluating the effects of lifestyle on trophic factor production, with resulting effects on circuit remodeling, synaptic function, and cognition. We believe that changes in trophic factor as a result of select experiences can affect neuronal health with profound consequences for cognitive function.

Education

B.A., University of Chile 1977
M.S., Neurobiology, University of Chile 1979
Ph.D., Anatomy & Cell Biology, University of California, Los Angeles 1986

Selected Publications

Molteni R, Wu A, Vaynman S, Ying Z, Barnard RJ, Gomez-Pinilla F., “Exercise reverses the harmful effects of consumption of a high-fat diet on synaptic and behavioral plasticity associated to the action of brain-derived neurotrophic factor”, Neuroscience, 123(2) : 429-40 (2004) .

Wu A, Ying Z, Gomez-Pinilla F., “The interplay between oxidative stress and brain-derived neurotrophic factor modulates the outcome of a saturated fat diet on synaptic plasticity and cognition”, Eur J Neurosci, 19(7): : 1699-707 (2004) .

Vaynman S, Ying Z, Gomez-Pinilla F., “Exercise induces BDNF and synapsin I to specific hippocampal subfields”, J Neurosci Res, 76(3): : 356-62 (2004) .

Griesbach GS, Hovda DA, Molteni R, Wu A, Gomez-Pinilla F., “Voluntary exercise following traumatic brain injury: brain-derived neurotrophic factor upregulation and recovery of function”, Neuroscience, 125(1) : 129-39 (2004) .

Hutchinson KJ, Gomez-Pinilla F, Crowe MJ, Ying Z, Basso DM., “Three exercise paradigms differentially improve sensory recovery after spinal cord contusion in rats”, Brain, 127(Pt 6): : 1403-14 (2004) .

Molteni R, Zheng JQ, Ying Z, Gomez-Pinilla F, Twiss JL., “Voluntary exercise increases axonal regeneration from sensory neurons”, Proc Natl Acad Sci U S A, 101(22) : :8473-8 (2004) .

Ying Z, Roy RR, Edgerton VR, Gomez-Pinilla F., “Voluntary exercise increases neurotrophin-3 and its receptor TrkC in the spinal cord”, Brain Res, 987(1) : 93-9 (2003) .

Vaynman S, Ying Z, Gomez-Pinilla F., “Interplay between brain-derived neurotrophic factor and signal transduction modulators in the regulation of the effects of exercise on synaptic-plasticity”, Neuroscience, 122(3) : 647-57 (2003) .

Gomez-Pinilla F, Ying Z, Roy RR, Molteni R, Edgerton VR., “Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity”, J Neurophysiol, 88(5) : 2187-95 (2002) .

Molteni, Ying, Z., and Gomez-Pinilla, F., “Differential expression of plasticity-related genes in the rat hippocampus after voluntary wheel running”, Eur. J. Neurosci, 16 (6) : 1107-1124 (2002) .

 

Elaine Hsiao

Elaine Hsiao

Associate Professor
De Logi Endowed Chair in Biological Sciences
Vice Chair of Postdoctoral Affairs

Email: ehsiao@g.ucla.edu
Office: 3825A MSB
Phone: (310) 825-2297
Website: http://hsiao.science/

Biography

Elaine is an Assistant Professor at UCLA, where she is interested in all things microbial, neural and immune. She completed her B.S. in Microbiology, Immunology and Molecular Genetics at UCLA, which sparked her love for molecular biology and bacteria. She went on to complete her Ph.D. in Neurobiology at Caltech, where she studied the neurobiological bases of autism and schizophrenia, with a focus on maternal effects on fetal development, and neuroimmune and microbial contributions to behavioral disorders. Inspired by the amazing and complex interactions between body systems, the Hsiao laboratory is investigating how “peripheral” changes in the immune system and resident microbiota impact the nervous system.

Research Interests

The gut microbiota is emerging as an important modulator of brain function and behavior, as several recent discoveries reveal substantial effects of the microbiome on neurophysiology, neurogenesis, blood brain barrier permeability, neuroimmunity, brain gene expression and animal behavior. Despite these findings supporting a “microbiome-gut-brain axis”, the molecular and cellular mechanisms that underlie interactions between the gut microbiota and brain remain poorly understood. To uncover these, the Hsiao laboratory is mining the human microbiota for microbial modulators of host neuroactive molecules, investigating the impact of microbiota-immune system interactions on neurodevelopment and examining the microbiome as an interface between gene-environment interactions in neurological diseases. We aim to dissect biological circuits for communication between the gut microbiota and nervous system, toward understanding fundamental biological pathways that influence brain and behavior. Situated at the interface of neurobiology, immunology and microbiology, we are using integrative systems approaches to study fundamental questions in biology: What are the effects of the microbiota on the nervous system? How do resident microbes communicate with the nervous system? Which individual species or communities confer particular functional effects? How do microbe-nervous system interactions impact health and disease? What, if any, are the potential evolutionary benefits for microbes to interact with the nervous system? Can rational modification of the microbiota be used to treat symptoms of neurological diseases?

Education

B.S., Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles 2006
Ph.D., Neurobiology, California Institute of Technology 2012

Selected Publications

Lynch JB, Hsiao EY (2019) ‘Microbiomes as sources of emergent host phenotypes.’ Science, 365 (6460): 1405-1409. PMID: 31604267

Fung TC, Vuong HE, Luna CDG, Pronovost GN, Aleksandrova AA, Riley NG, Vavilina A, McGinn J, Rendon T, Forrest LR, Hsiao EY (2019) ‘Intestinal serotonin and fluoxetine exposure modulate bacterial colonization in the gut.’ Nat Microbiol, 4 (12): 2064-2073. PMID: 31477894

Lum GR, Olson CA, Hsiao EY (2020) ‘Emerging roles for the intestinal microbiome in epilepsy.’ Neurobiol Dis, 135 (): 104576. PMID: 31445165

Pronovost GN, Hsiao EY (2019) ‘Perinatal Interactions between the Microbiome, Immunity, and Neurodevelopment.’ Immunity, 50 (1): 18-36. PMID: 30650376

Hsiao E. Y., “The neuroimmune collective, in “Voices: The Next Quarter Century””, Immunity, 50 : 769-777 (2019) .

Olson C. A., Vuong H. E., Yano J. M., Liang Q. Y., Nusbaum D. J., Hsiao E. Y., “The gut microbiota mediates the anti-seizure effects of the ketogenic diet”, Cell, 173 : 1728-1741 (2018) .

Hsiao EY (2018) Decoding states and contexts, in “Setting the Stage for the Next Generation of Neuroscience”. Neuron. 99:11-12. PMID: 30001505.

Fung TC, Olson CA, Hsiao EY (2017) ‘Interactions between the microbiota, immune and nervous systems in health and disease.’ Nat Neurosci, 20 (2): 145-155. PMID: 28092661

Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L, Nagler CR, Ismagilov RF, Mazmanian SK, Hsiao EY (2015) ‘Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis.’ Cell, 161 (2): 264-76. PMID: 25860609

Walter Metzner

Walter Metzner

Professor

Email: metzner@ucla.edu
Office: 4365 LS
Phone: (310) 206-2023

Research Interests

Sensory processing/motor control, especially auditory feedback control of vocalization; Behavioral Neuroscience (Neuroethology)

Education

B.S., University of Erlangen, Germany 1981
M.S., Zoology, University of Munich/Germany Department of Zoology 1984
Ph.D., Zoology, University of Munich/Germany Department of Zoology 1989

 

Ketema Paul

Ketema Paul

Professor

Email: ketema.paul@ucla.edu
Office: 1014 TLSB
Phone: (310) 794-7755
Website: https://uclapaullab.wixsite.com/ucla-paul-lab

Biography

After receiving a bachelor’s degree in biology from Howard University I went on to study neurobiology and circadian biology at Georgia State University in Atlanta, Georgia where I received my doctorate in 2003. I completed a postdoctoral fellowship at Northwestern University in Evanston Illinois in 2006 at the Center for Sleep and Circadian Biology under the guidance of Dr. Fred Turek, after which I accepted a faculty position at the Morehouse School of Medicine (MSM). I spent ten years at MSM and joined the faculty at UCLA in 2016.

Research Interests

My work examines the neural and genetic regulation of sleep regulatory mechanisms. My research program currently has three foci: 1) to examine sex differences in sleep regulatory mechanisms, 2) to investigate the role of circadian molecules on the ability to recover from sleep loss, and 3) to determine how genetic heterogeneity contributes to resilience against the negative effects of sleep loss. My lab has adopted a forward genetics approach in mice to uncover the core genes responsible for sleep-wake regulation and sleep homeostasis. Another avenue of interest in my lab is the circadian expression of sleep-regulatory genes in isolated peripheral blood mononuclear cells from patients with Alzheimer’s Disease. These studies are expected to identify novel sleep-regulatory genes and lead to the development of new therapeutic targets and improved treatments for sleep-related disorders.

Education

B.S., Biology, Howard University 1994
Ph.D., Biology, Georgia State University 2003

Selected Publications

Polyunsaturated Fatty Acids Mend Macrophage Transcriptome, Glycome, and Phenotype in the Patients with Neurodegenerative Diseases, Including Alzheimer’s Disease. J Alzheimers Dis. 2023; 91(1):245-261. Dover M, Moseley T, Biskaduros A, Paulchakrabarti M, Hwang SH, Hammock B, Choudhury B, Kaczor-Urbanowicz KE, Urbanowicz A, Morselli M, Dang J, Pellegrini M, Paul K, Bentolila LA, Fiala M. PMID: 36373322.

Non-rapid eye movement sleep determines resilience to social stress. Elife. 2022 09 23; 11. Bush BJ, Donnay C, Andrews EA, Lewis-Sanders D, Gray CL, Qiao Z, Brager AJ, Johnson H, Brewer HCS, Sood S, Saafir T, Benveniste M, Paul KN, Ehlen JC. PMID: 36149059; PMCID: PMC9586557.

Estrogen-sensitive medial preoptic area neurons coordinate torpor in mice. Nat Commun. 2020 12 11; 11(1):6378. Zhang Z, Reis FMCV, He Y, Park JW, DiVittorio JR, Sivakumar N, van Veen JE, Maesta-Pereira S, Shum M, Nichols I, Massa MG, Anderson S, Paul K, Liesa M, Ajijola OA, Xu Y, Adhikari A, Correa SM. PMID: 33311503; PMCID: PMC7732979.

Sleep loss mediates the effect of stress on nitrergic signaling in female mice. Neurosci Lett. 2021 01 01; 740:135362. Chiem E, Nichols I, Van C, Kori S, Paul K. PMID: 33166635.

Omega-3 Fatty Acids Increase Amyloid-β Immunity, Energy, and Circadian Rhythm for Cognitive Protection of Alzheimer’s Disease Patients Beyond Cholinesterase Inhibitors. J Alzheimers Dis. 2020; 75(3):993-1002. Fiala M, Lau YCC, Aghajani A, Bhargava S, Aminpour E, Kaczor-Urbanowicz KE, Mirzoyan H, Nichols I, Ko MW, Morselli M, Santana J, Dang J, Sayre J, Paul K, Pellegrini M. PMID: 32390637.

Muscle, a conduit to brain for hormonal control of behavior. Horm Behav. 2018 09; 105:58-65.Schlinger BA, Paul K, Monks DA. PMID: 30040953.

Ehlen, J.C., Brager, A.J., Baggs, J., Pinckney, L., Gray, C.L., Debruyne, J.P., Esser, K.A., Takahashi, J.S., Paul, K.N., “Bmal1 function in skeletal muscle regulates sleep”, eLife, 1-15 (2017) .

Clark, K.P., Ehlen, J.C., Paul, K.N., “Race and Gender Disparities in Sleep-Disordered Breathing”, Journal of Sleep Disorders: Treatment & Care, 6 (1): 1-4 (2017) .

Brager A.J., Heemstra, L., Bhambra, R., Ehlen, J.C., Esser, K., Paul, K.N., Novak, C. M., “Homeostatic effects of exercise and sleep on metabolic processes in mice with an overexpressed skeletal muscle clock”, Biochimie, 132 : 161-165 (2017) .

Brager, A.J., Yang, T., Ehlen, J.C., Simon, R.P., Meller, R., Paul, K.N., “Sleep is critical for remote preconditioning-induce neuroprotection”, Sleep, 39 : 2033-2040 (2016) .

Ehlen, J.C., Jones, K.A., Pinckney, L., Gray, C.L. Burette, S., Weinberg, R.J., Evans, J.A., Brager, A., Zylka, M.J., Paul, K.N., Philphot, B.D., Debruyne, J.P, “Maternal Ube3a loss disrupts sleep homeostasis but leaves circadian rhythmicity largely intact”, Sleep, 35 : 13587-13598 (2015) .

Evans, J.A., Suen, T-C., Calif, B., Mitchell, A., Castanon-Cervantes, O., Baker, K.M., Kloehn, I., Baba, K., Teubner, B.J.W., Ehlen, J.C., Paul, K.N., Bartness, T.J., Tosini, G., Leise, T.L., Davidson, A.J, “Shell neurons of the master circadian clock coordinate the phase of tissue clocks throughout the brain and body”, Sleep, 13 : 1-15 (2015) .

Jefferson, F., Ehlen, J.C., Williams, N.S., Paul, K.N, “A dopamine D2-receptor agonist attenuates the ability of stress to alter sleep in mice”, Sleep, 155 : 4411-4421 (2014) .

Ehlen, J.C., Jefferson, F. Brager, A.J., Benveniste, M., Paul, K.N., “Period-Amplitude Analysis Reveals Wake-Dependent Changes in the Electroencephalogram during Sleep Deprivation”, Sleep, 36 : 1723-1735 (2013) .

Brager, A.J., Ehlen, J.C., Castanon-Cervantes, O., Natarajan, D., Delisser, P., Davidson, A., Paul, K.N, “Sleep loss and inflammatory markers under chronic environmental circadian disruption”, Sleep, 8 : 1-8 (2013) .

Ehlen, J.C., Hesse S., Pinckney, L., Paul, K.N, “Sex chromosomes regulate nighttime sleep propensity during recovery from sleep loss”, Sleep, 8 : 1-6 (2013) .

 

Patricia Phelps

Patricia Phelps

Professor
Vice Chair of Undergraduate Education

Email: pphelps@physci.ucla.edu
Office: 1024 TLSB
Phone: (310) 825-7264
Website: http://www.physci.ucla.edu/research/phelps/index.php

Biography

Dr. Patty Phelps received her BS and BA degrees from Washington University in St. Louis and her PhD from the Department of Anatomy at UCLA. She then moved to the City of Hope Research Institute in Duarte, California where she received her Postdoctoral training in the Neuroscience Division with Dr. James Vaughn. In 1995, she joined UCLA as an Assistant Professor in the Department of Physiological Science, which is now named the Department of Integrative Biology and Physiology. For many years Dr. Phelps has served as the Vice-Chair for Undergraduate Education in the department and also was the Faculty Director for the Amgen Scholars Program from 2006-2017. Her teaching focuses on the Systems Anatomy class taken by all entering Physiological Science majors and her upper division elective on the “Principles of Nervous System Development.” Based on the extensive multimedia teaching tools she developed and uses in her classes, together with her teaching excellence, she received the UCLA Distinguished Teaching award in 2011.

Research Interests

Our research focuses on the molecular and cellular interactions that control spinal cord development and regeneration after injury. Currently we study the effects of neuronal migratory errors identified in the dorsal horn of the reeler spinal cord. Reelin is a secreted glycoprotein that binds the lipoprotein receptors Vldlr and Apoer2, is internalized, and activates a tyrosine kinase cascade that phosphorylates the intracellular adaptor protein Disabled-1 (Dab1). The Reelin-signaling pathway regulates neuronal positioning in the spinal cord in a cell-specific manner; distinct subsets of neurons sustain migratory errors while others are correctly located. Our laboratory has uncovered migratory errors in the dorsal horn of reeler and dab1 mutants during development and in adults. Importantly, both reeler and dab1 mutants show an increased sensitivity to heat and a profound reduction in mechanical sensitivity. Our findings indicate that Reelin and Dab1-expressing neurons are essential contributors to the normal development of circuits that underlie thermal and mechanical pain processing.

A second focus of the laboratory is to study axon regeneration following complete spinal cord transection. Together with Dr. Edgerton’s lab at UCLA we have completed four extensive studies in which olfactory bulb-derived olfactory ensheathing cells (OECs) were transplanted into the spinal cord after a transection at thoracic level T8. We found that adult spinal rats transplanted with OECs had, relative to control rats receiving medium or fibroblast transplants: 1) improved locomotor performance during hindlimb treadmill stepping, 2) motor evoked potentials induced with transcranial electric stimulation that were lost following re-transection above the original injury, 3) evidence of supraspinal and propriospinal regeneration, and 4) a modification of the lesion site in which OECs align with astrocytes to facilitate axon outgrowth across the injury. Results from tissue culture experiments that mimic the inhibitory glial scar at the lesion site show that OECs directly enhance neurite outgrowth compared to fibroblast controls.

Education

B.A., School of Liberal Arts, Washington University, St. Louis 1970
B.S., School of Medicine, Department of Occupational Therapy, Washington University, St. Louis 1970
Ph.D., Anatomy and Cell Biology, University of California, Los Angeles 1982

Selected Publications

Wang, X, Yvonne, GM, Cilluffo, M, Kim, AS, Basbaum, AI, and Phelps, PE, “Mispositioned Neurokinin-1 receptor-expressing neurons underlie heat hyperalgesia in Disabled-1 mutant mice”, eNeuro, 6 (e0131-19): 1-16 (2019) [link].

Thornton, MA, Mehta, MD, Morad, TT, Ingraham, KL, Khankan, RR, Griffis, KG, Yeung, AK, Zhong, H, Roy, RR, Edgerton, VR, Phelps, PE, “Evidence of axon connectivity across a spinal cord transection in rats treated with epidural stimulation and motor training combined with olfactory ensheathing cell transplantation”, Expt. Neurol., 309 : 119-133 (2018) [link].

Yvone, G.M., H.H. Zhao-Fleming, J.C. Udeochu, C.L. Chavez-Martinez, A. Wang, M. Hirose- Ikeda, and P.E. Phelps, “Disabled-1 dorsal horn neurons co-express Lmx1b and function in nociceptive circuits”, Eur. J. Neurosci, 45 : 733-747 (2017) [link].

Khankan, R.R., K.G. Griffis, J.R. Haggerty-Skeans, H. Zhong, R.R. Roy, V.R. Edgerton, and P.E. Phelps, “Olfactory ensheathing cell transplantation after a complete spinal cord transection mediates neuroprotective and immunomodulatory mechanisms to facilitate regeneration”, J. Neurosci., 36 : 6269-6286 (2016) [link].

Fraley, E.R., Z.D. Burkett, N. F. Day, B.A. Schwartz, P.E. Phelps, and S.A. White, “Mice with Dab1 or Vldlr insufficiency exhibit abnormal neonatal vocalization patterns”, Scientific Report, 6:25807 : 1-12 (2016) [link].

Abadesco, A.D., M. Cilluffo, G.M. Yvone, E.M. Carpenter, B.W. Howell, and P.E. Phelps, “Novel Disabled-1-expressing neurons identified in adult brain and spinal cord”, Eur. J. Neurosci., 39 : 579-592 (2014) .

Wang, X., A.H.Babayan, A.I. Basbaum and P.E. Phelps, “Loss of the Reelin-signaling pathway differentially disrupts heat, mechanical and chemical nociceptive processing”, Neuroscience, 226 : 441-450 (2012) .

Ziegler, M.D., D. Hsu, A. Takeoka, H. Zhong, A. Ramon-Cueto, P.E. Phelps, R.R. Roy, and V.R. Edgerton, “Further evidence of Olfactory Ensheathing Glia facilitating axonal regeneration after a complete spinal cord transection”, Expt. Neurol., 229 : 109-119 (2011) .

Takeoka, T., D.L. Jindrich, C. Munoz-Quiles, H. Zhong, R. van den Brand, D.L. Pham, M.D. Ziegler, A. Ramon-Cueto, R.R. Roy, V.R. Edgerton, and P.E. Phelps, “Axon regeneration can facilitate or suppress hindlimb function after Olfactory Ensheathing Glia transplantation”, J. Neurosci., 31 : 4298-4310 (2011) .