Posts classified under: Research Mentors

Jose Rodriguez, Ph.D.

Biography

Prof. Rodriguez studies the complex architecture of biological systems – from single biomolecules to cellular assemblies – at high resolution. His work is largely based on diffraction phenomena and combines computational, biochemical and biophysical experiments. The development of new methods is central to this work, particularly using emerging technologies in cryo-electron microscopy, nano and coherent x-ray diffraction, and macromolecular design. Combined, these tools can reveal undiscovered structures that broadly influence chemistry, biology, and medicine.

He is a true Bruin. He received his B.S. in BioPhysics at UCLA and his Ph.D. in Molecular Biology, also at UCLA.

Gina Poe, Ph.D.

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

Ketema Paul, Ph.D.

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 genetic regulation of sleep and more importantly, how genetic heterogeneity influences the ability to recover from sleep loss. My research program currently has two foci: 1) to determine if disruptions of biological timing result in sleep-wake disorders and if so, which specific genes are involved and, 2) to determine if sex differences in the risk and severity of sleep abnormalities are chromosomally driven. My lab has recently undertaken a forward genetics approach to identify novel sleep genes. We have characterized a variety of sleep phenotypes in inbred mouse strains in sleep-replete and sleep-deprived conditions. We are expanding this dataset to provide sufficient statistical power for quantitative trait loci (QTL) analysis and subsequent follow-up studies. This endeavor combines a well-established paradigm of comparative phenotyping of a genetically tractable animal model with powerful genetic mapping tools to identify novel sleep-regulatory genes. Consequently, these experiments will not only identify new sleep genes, they will also help verify and clarify previously mapped genes whose roles are not yet clearly defined.

 

Education

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

 

Selected Publications

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) .

Melody Li , Ph.D.

Research Interests

Mosquito-borne viruses are emerging pathogens that cause devastating outbreaks worldwide as globalization and climate change facilitate their spread beyond their endemic regions. The Li laboratory studies the host type I interferon (IFN) response to medically relevant mosquito-borne viruses such as alphaviruses and flaviviruses. Cellular sensing of viral pathogens triggers IFN production and signaling leading to expression of a wide array of IFN-stimulated genes (ISGs) with antiviral activities. In particular, zinc finger antiviral protein (ZAP) targets diverse viruses by recognition of CG dinucleotide, recruitment of cellular RNA decay machineries, and suppression of viral translation. However, what determines the broad yet specific activity of ZAP is poorly understood. We discovered that ZAP co-opts the host ubiquitination pathway to block viral translation, and some alphaviruses have evolved strategies to evade ZAP antiviral action. Understanding how cellular and viral processes modulate ISG antiviral function will shed light on the molecular mechanisms driving viral virulence and pathogenesis. In addition, recent studies by other groups have pointed to an unexpected role of IFNs; both type I and type III IFNs can decrease blood-brain barrier permeability in a mouse viral infection model. We are interested in the pro-barrier functions of IFNs as our previous work suggested that IRF2, a negative regulator of IFN, protects the central nervous system from alphaviral invasion and encephalitis. A full characterization of ISG activities will elucidate the basic biology of host pathogen recognition and uncover cellular processes required for the success or suppression of viral replication, which will inform the development of broad-spectrum antiviral therapeutic.

Biography

Dr. Li is an Assistant Professor of Microbiology, Immunology and Molecular Genetics at UCLA. She received her Bachelors of Science Degree (B.S.) from University of California, Irvine in 2006, and her Doctor of Philosophy Degree (Ph.D.) in Microbiology from University of Washington, Seattle in 2011. Dr. Li’s thesis work elucidated the functional consequences of polymorphisms in the human APOBEC3H gene, which encodes for a cytosine deaminase that is antiviral against human immunodeficiency virus type 1 (HIV-1). Dr. Li subsequently completed her postdoctoral work at Rockefeller University where she studied the antiviral mechanisms and regulation of the host interferon response targeting alphaviruses. Dr. Li established her own laboratory at UCLA in 2017, and her research focuses on elucidating the role of ISGs in innate immunity and blood-brain barrier integrity with broad implications for the treatment of viral infections, autoimmunity and neurological diseases. She serves on the UCLA Basic/Translational COVID-19 Research Committee.

Publications 

Garcia G Jr, Paul S, Beshara S, Ramanujan VK, Ramaiah A, Nielsen-Saines K, Li MMH, French SW, Morizono K, Kumar A, Arumugaswami V. Hippo Signaling Pathway Has a Critical Role in Zika Virus Replication and in the Pathogenesis of Neuroinflammation. Am J Pathol. 2020 Apr;190(4):844-861. doi: 10.1016/j.ajpath.2019.12.005. Epub 2020 Feb 5. PMID: 32035058; PMCID: PMC7163250.

Li MMH, Aguilar EG, Michailidis E, Pabon J, Park P, Wu X, de Jong YP, Schneider WM, Molina H, Rice CM, MacDonald MR. Characterization of Novel Splice Variants of Zinc Finger Antiviral Protein (ZAP). J Virol. 2019 Aug 28;93(18):e00715-19. doi: 10.1128/JVI.00715-19. PMID: 31118263; PMCID: PMC6714797.

Law LMJ, Razooky BS, Li MMH, You S, Jurado A, Rice CM, MacDonald MR. ZAP’s stress granule localization is correlated with its antiviral activity and induced by virus replication. PLoS Pathog. 2019 May 22;15(5):e1007798. doi: 10.1371/journal.ppat.1007798. PMID: 31116799; PMCID: PMC6548403.

Wu X, Dao Thi VL, Huang Y, Billerbeck E, Saha D, Hoffmann HH, Wang Y, Silva LAV, Sarbanes S, Sun T, Andrus L, Yu Y, Quirk C, Li M, MacDonald MR, Schneider WM, An X, Rosenberg BR, Rice CM. Intrinsic Immunity Shapes Viral Resistance of Stem Cells. Cell. 2018 Jan 25;172(3):423-438.e25. doi: 10.1016/j.cell.2017.11.018. Epub 2017 Dec 14. PMID: 29249360; PMCID: PMC5786493.

Li Melody M H, Lau Zerlina, Cheung Pamela, Aguilar Eduardo G, Schneider William M, Bozzacco Leonia, Molina Henrik, Buehler Eugen, Takaoka Akinori, Rice Charles M, Felsenfeld Dan P, MacDonald Margaret R TRIM25 Enhances the Antiviral Action of Zinc-Finger Antiviral Protein (ZAP). PLoS pathogens. 2017; 13(1): e1006145.

Li Melody M H, Bozzacco Leonia, Hoffmann Hans-Heinrich, Breton Gaëlle, Loschko Jakob, Xiao Jing W, Monette Sébastien, Rice Charles M, MacDonald Margaret R Interferon regulatory factor 2 protects mice from lethal viral neuroinvasion. The Journal of experimental medicine. 2016; 213(13): 2931-2947.

Wang Xinlu, Li Melody M H, Zhao Jing, Li Shenglan, MacDonald Margaret R, Rice Charles M, Gao Xiang, Gao Guangxia Sindbis Virus Can Exploit a Host Antiviral Protein To Evade Immune Surveillance. Journal of virology. 2016; 90(22): 10247-10258.

Li Melody M H, MacDonald Margaret R Polyamines: Small Molecules with a Big Role in Promoting Virus Infection. Cell host & microbe. 2016; 20(2): 123-4.

Bozzacco Leonia, Yi Zhigang, Andreo Ursula, Conklin Claire R, Li Melody M H, Rice Charles M, MacDonald Margaret R Chaperone-Assisted Protein Folding Is Critical for Yellow Fever Virus NS3/4A Cleavage and Replication. Journal of virology. 2016; 90(6): 3212-28.

Li Melody M H, MacDonald Margaret R, Rice Charles M To translate, or not to translate: viral and host mRNA regulation by interferon-stimulated genes. Trends in cell biology. 2015; 25(6): 320-9.

Charron Guillaume, Li Melody M H, MacDonald Margaret R, Hang Howard C Prenylome profiling reveals S-farnesylation is crucial for membrane targeting and antiviral activity of ZAP long-isoform. Proceedings of the National Academy of Sciences of the United States of America. 2013; 110(27): 11085-90.

Karki Sophiya, Li Melody M H, Schoggins John W, Tian Suyan, Rice Charles M, MacDonald Margaret R Multiple interferon stimulated genes synergize with the zinc finger antiviral protein to mediate anti-alphavirus activity. PloS one. 2012; 7(5): e37398.

Li Melody M H, Emerman Michael Polymorphism in human APOBEC3H affects a phenotype dominant for subcellular localization and antiviral activity. Journal of virology. 2011; 85(16): 8197-207.

Li Melody M H, Wu Lily I, Emerman Michael The range of human APOBEC3H sensitivity to lentiviral Vif proteins. Journal of virology. 2010; 84(1): 88-95.

OhAinle Molly, Kerns Julie A, Li Melody M H, Malik Harmit S, Emerman Michael Antiretroelement activity of APOBEC3H was lost twice in recent human evolution. Cell host & microbe. 2008; 4(3): 249-59.

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