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1. A cross-disease resource of living human microglia identifies disease-enriched subsets and tool compounds recapitulating microglial states

Author

Tuddenham, John F., Taga, Mariko, Haage, Verena, Marshe, Victoria S., Roostaei, Tina, White, Charles, Lee, Annie J., Fujita, Masashi, Khairallah, Anthony, Zhang, Ya, Green, Gilad, Hyman, Bradley, Frosch, Matthew, Hopp, Sarah, Beach, Thomas G., Serrano, Geidy E., Corboy, John, Habib, Naomi, Klein, Hans-Ulrich, Soni, Rajesh Kumar, Teich, Andrew F., Hickman, Richard A., Alcalay, Roy N., Shneider, Neil, Schneider, Julie, Sims, Peter A., Bennett, David A., Olah, Marta, Menon, Vilas, and De Jager, Philip L.

Published
2024
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2. Real-world experience with circulating tumor DNA in cerebrospinal fluid from patients with central nervous system tumors

Author

Hickman, Richard A., Miller, Alexandra M., Holle, Bridget M., Jee, Justin, Liu, Si-Yang, Ross, Dara, Yu, Helena, Riely, Gregory J., Ombres, Christina, Gewirtz, Alexandra N., Reiner, Anne S., Nandakumar, Subhiksha, Price, Adam, Kaley, Thomas J., Graham, Maya S., Vanderbilt, Chad, Rana, Satshil, Hill, Katherine, Chabot, Kiana, Campos, Carl, Nafa, Khedoudja, Shukla, Neerav, Karajannis, Matthias, Li, Bob, Berger, Michael, Ladanyi, Marc, Pentsova, Elena, Boire, Adrienne, Brannon, A. Rose, Bale, Tejus, Mellinghoff, Ingo K., and Arcila, Maria E.

Published
2024
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3. Multi-omic analysis of Huntington’s disease reveals a compensatory astrocyte state

Author

Paryani, Fahad, Kwon, Ji-Sun, Ng, Christopher W., Jakubiak, Kelly, Madden, Nacoya, Ofori, Kenneth, Tang, Alice, Lu, Hong, Xia, Shengnan, Li, Juncheng, Mahajan, Aayushi, Davidson, Shawn M., Basile, Anna O., McHugh, Caitlin, Vonsattel, Jean Paul, Hickman, Richard, Zody, Michael C., Housman, David E., Goldman, James E., Yoo, Andrew S., Menon, Vilas, and Al-Dalahmah, Osama

Published
2024
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5. Huntington disease oligodendrocyte maturation deficits revealed by single-nucleus RNAseq are rescued by thiamine-biotin supplementation

Author

Lim, Ryan G, Al-Dalahmah, Osama, Wu, Jie, Gold, Maxwell P, Reidling, Jack C, Tang, Guomei, Adam, Miriam, Dansu, David K, Park, Hye-Jin, Casaccia, Patrizia, Miramontes, Ricardo, Reyes-Ortiz, Andrea M, Lau, Alice, Hickman, Richard A, Khan, Fatima, Paryani, Fahad, Tang, Alice, Ofori, Kenneth, Miyoshi, Emily, Michael, Neethu, McClure, Nicolette, Flowers, Xena E, Vonsattel, Jean Paul, Davidson, Shawn, Menon, Vilas, Swarup, Vivek, Fraenkel, Ernest, Goldman, James E, and Thompson, Leslie M

Subjects
Biological Sciences, Genetics, Brain Disorders, Neurodegenerative, Neurosciences, Huntington's Disease, Human Genome, Rare Diseases, Nutrition, 2.1 Biological and endogenous factors, Neurological, Animals, Humans, Mice, Biotin, Dietary Supplements, Disease Models, Animal, Huntington Disease, Mice, Transgenic, Nerve Tissue Proteins, Oligodendroglia, Solitary Nucleus, Thiamine
Abstract

The complexity of affected brain regions and cell types is a challenge for Huntington's disease (HD) treatment. Here we use single nucleus RNA sequencing to investigate molecular pathology in the cortex and striatum from R6/2 mice and human HD post-mortem tissue. We identify cell type-specific and -agnostic signatures suggesting oligodendrocytes (OLs) and oligodendrocyte precursors (OPCs) are arrested in intermediate maturation states. OL-lineage regulators OLIG1 and OLIG2 are negatively correlated with CAG length in human OPCs, and ATACseq analysis of HD mouse NeuN-negative cells shows decreased accessibility regulated by OL maturation genes. The data implicates glucose and lipid metabolism in abnormal cell maturation and identify PRKCE and Thiamine Pyrophosphokinase 1 (TPK1) as central genes. Thiamine/biotin treatment of R6/1 HD mice to compensate for TPK1 dysregulation restores OL maturation and rescues neuronal pathology. Our insights into HD OL pathology spans multiple brain regions and link OL maturation deficits to abnormal thiamine metabolism.

Published
2022

6. Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis

Author

Dewan, Ramita, Chia, Ruth, Ding, Jinhui, Hickman, Richard A, Stein, Thor D, Abramzon, Yevgeniya, Ahmed, Sarah, Sabir, Marya S, Portley, Makayla K, Tucci, Arianna, Ibáñez, Kristina, Shankaracharya, FNU, Keagle, Pamela, Rossi, Giacomina, Caroppo, Paola, Tagliavini, Fabrizio, Waldo, Maria L, Johansson, Per M, Nilsson, Christer F, Rowe, James B, Benussi, Luisa, Binetti, Giuliano, Ghidoni, Roberta, Jabbari, Edwin, Viollet, Coralie, Glass, Jonathan D, Singleton, Andrew B, Silani, Vincenzo, Ross, Owen A, Ryten, Mina, Torkamani, Ali, Tanaka, Toshiko, Ferrucci, Luigi, Resnick, Susan M, Pickering-Brown, Stuart, Brady, Christopher B, Kowal, Neil, Hardy, John A, Van Deerlin, Vivianna, Vonsattel, Jean Paul, Harms, Matt, Morris, Christopher M, Ferrari, Raffaele, Landers, John E, Chiò, Adriano, Gibbs, Jesse Raphael, Dalgard, Clifton L, Scholz, Sonja W, Traynor, Bryan J, Adeleye, Adelani, Alba, Camille, Bacikova, Dagmar, Hupalo, Daniel N, Martinez, Elisa McGrath, Pollard, Harvey B, Sukumar, Gauthaman, Soltis, Anthony R, Tuck, Meila, Zhang, Xijun, Wilkerson, Matthew D, Smith, Bradley N, Ticozzi, Nicola, Fallini, Claudia, Gkazi, Athina Soragia, Topp, Simon D, Kost, Jason, Scotter, Emma L, Kenna, Kevin P, Miller, Jack W, Tiloca, Cinzia, Vance, Caroline, Danielson, Eric W, Troakes, Claire, Colombrita, Claudia, Al-Sarraj, Safa, Lewis, Elizabeth A, King, Andrew, Calini, Daniela, Pensato, Viviana, Castellotti, Barbara, de Belleroche, Jacqueline, Baas, Frank, Asbroek, Anneloor LMA ten, Sapp, Peter C, McKenna-Yasek, Diane, McLaughlin, Russell L, Polak, Meraida, Asress, Seneshaw, Esteban-Pérez, Jesús, Muñoz-Blanco, José Luis, Stevic, Zorica, D’Alfonso, Sandra, Mazzini, Letizia, Comi, Giacomo P, Del Bo, Roberto, Ceroni, Mauro, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, and van Rheenen, Wouter

Subjects
Genetics, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Clinical Research, Neurodegenerative, Acquired Cognitive Impairment, Dementia, Frontotemporal Dementia (FTD), Alzheimer's Disease Related Dementias (ADRD), ALS, Rare Diseases, Brain Disorders, Neurosciences, Huntington's Disease, 2.1 Biological and endogenous factors, Aetiology, Neurological, Amyotrophic Lateral Sclerosis, DNA Repeat Expansion, Frontotemporal Dementia, Humans, Huntingtin Protein, Mutation, Whole Genome Sequencing, American Genome Center, FALS Sequencing Consortium, Genomics England Research Consortium, International ALS/FTD Genomics Consortium, International FTD Genetics Consortium, International LBD Genomics Consortium, NYGC ALS Consortium, PROSPECT Consortium, amyotrophic lateral sclerosis, frontotemporal dementia, huntingtin, repeat expansions, whole-genome sequencing, Psychology, Cognitive Sciences, Neurology & Neurosurgery
Abstract

We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered.

Published
2021

12. Pituitary neuroendocrine tumors: a model for neuroendocrine tumor classification

Author

Asa, Sylvia L., Mete, Ozgur, Cusimano, Michael D., McCutcheon, Ian E., Perry, Arie, Yamada, Shozo, Nishioka, Hiroshi, Casar-Borota, Olivera, Uccella, Silvia, La Rosa, Stefano, Grossman, Ashley B., Ezzat, Shereen, International Pituitary Pathology, Asioli, Sofia, Bozkurt, Süheyla Uyar, Comunoglu, Nil, Cossu, Giulia, Earls, Peter, Gazioglu, Nuperi, Hickman, Richard A., Ikeda, Hidetoshi, Manojlovic-Gacic, Emilija, Messerer, Mahmoud, Öz, Buge, Pakbaz, Sara, Roncaroli, Federico, Saeger, Wolfgang, Turchini, John, and Yarman, Sema

Published
2021
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13. R1441G but not G2019S mutation enhances LRRK2 mediated Rab10 phosphorylation in human peripheral blood neutrophils

Author

Fan, Ying, Nirujogi, Raja S., Garrido, Alicia, Ruiz-Martínez, Javier, Bergareche-Yarza, Alberto, Mondragón-Rezola, Elisabet, Vinagre-Aragón, Ana, Croitoru, Ioana, Gorostidi Pagola, Ana, Paternain Markinez, Laura, Alcalay, Roy, Hickman, Richard A., Düring, Jonas, Gomes, Sara, Pratuseviciute, Neringa, Padmanabhan, Shalini, Valldeoriola, Francesc, Pérez Sisqués, Leticia, Malagelada, Cristina, Ximelis, Teresa, Molina Porcel, Laura, Martí, Maria José, Tolosa, Eduardo, Alessi, Dario R., and Sammler, Esther M.

Published
2021
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14. Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis

Author

Adeleye, Adelani, Alba, Camille, Bacikova, Dagmar, Hupalo, Daniel N., Martinez, Elisa McGrath, Pollard, Harvey B., Sukumar, Gauthaman, Soltis, Anthony R., Tuck, Meila, Zhang, Xijun, Wilkerson, Matthew D., Smith, Bradley N., Ticozzi, Nicola, Fallini, Claudia, Gkazi, Athina Soragia, Topp, Simon D., Kost, Jason, Scotter, Emma L., Kenna, Kevin P., Miller, Jack W., Tiloca, Cinzia, Vance, Caroline, Danielson, Eric W., Troakes, Claire, Colombrita, Claudia, Al-Sarraj, Safa, Lewis, Elizabeth A., King, Andrew, Calini, Daniela, Pensato, Viviana, Castellotti, Barbara, de Belleroche, Jacqueline, Baas, Frank, ten Asbroek, Anneloor L.M.A., Sapp, Peter C., McKenna-Yasek, Diane, McLaughlin, Russell L., Polak, Meraida, Asress, Seneshaw, Esteban-Pérez, Jesús, Muñoz-Blanco, José Luis, Stevic, Zorica, D’Alfonso, Sandra, Mazzini, Letizia, Comi, Giacomo P., Del Bo, Roberto, Ceroni, Mauro, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, van Rheenen, Wouter, Diekstra, Frank P., Rademakers, Rosa, van Blitterswijk, Marka, Boylan, Kevin B., Lauria, Giuseppe, Duga, Stefano, Corti, Stefania, Cereda, Cristina, Corrado, Lucia, Sorarù, Gianni, Williams, Kelly L., Nicholson, Garth A., Blair, Ian P., Leblond-Manry, Claire, Rouleau, Guy A., Hardiman, Orla, Morrison, Karen E., Veldink, Jan H., van den Berg, Leonard H., Al-Chalabi, Ammar, Pall, Hardev, Shaw, Pamela J., Turner, Martin R., Talbot, Kevin, Taroni, Franco, García-Redondo, Alberto, Wu, Zheyang, Gellera, Cinzia, Ratti, Antonia, Brown, Robert H., Jr., Shaw, Christopher E., Ambrose, John C., Arumugam, Prabhu, Baple, Emma L., Bleda, Marta, Boardman-Pretty, Freya, Boissiere, Jeanne M., Boustred, Christopher R., Brittain, H., Caulfield, Mark J., Chan, Georgia C., Craig, Clare E.H., Daugherty, Louise C., de Burca, Anna, Devereau, Andrew, Elgar, Greg, Foulger, Rebecca E., Fowler, Tom, Furió-Tarí, Pedro, Hackett, Joanne M., Halai, Dina, Hamblin, Angela, Henderson, Shirley, Holman, James E., Hubbard, Tim J.P., Jackson, Rob, Jones, Louise J., Kasperaviciute, Dalia, Kayikci, Melis, Lahnstein, Lea, Lawson, Kay, Leigh, Sarah E.A., Leong, Ivonne U.S., Lopez, Javier F., Maleady-Crowe, Fiona, Mason, Joanne, McDonagh, Ellen M., Moutsianas, Loukas, Mueller, Michael, Murugaesu, Nirupa, Need, Anna C., Odhams, Chris A., Patch, Christine, Perez-Gil, Daniel, Polychronopoulos, Dimitris, Pullinger, John, Rahim, Tahrima, Rendon, Augusto, Riesgo-Ferreiro, Pablo, Rogers, Tim, Savage, Kevin, Sawant, Kushmita, Scott, Richard H., Siddiq, Afshan, Sieghart, Alexander, Smedley, Damian, Smith, Katherine R., Sosinsky, Alona, Spooner, William, Stevens, Helen E., Stuckey, Alexander, Sultana, Razvan, Thomas, Ellen R.A., Thompson, Simon R., Tregidgo, Carolyn, Walsh, Emma, Watters, Sarah A., Welland, Matthew J., Williams, Eleanor, Witkowska, Katarzyna, Wood, Suzanne M., Zarowiecki, Magdalena, Arepalli, Sampath, Auluck, Pavan, Baloh, Robert H., Bowser, Robert, Brice, Alexis, Broach, James, Camu, William, Chiò, Adriano, Cooper-Knock, John, Corcia, Philippe, Drepper, Carsten, Drory, Vivian E., Dunckley, Travis L., Faghri, Faraz, Farren, Jennifer, Feldman, Eva, Floeter, Mary Kay, Fratta, Pietro, Gerhard, Glenn, Gibson, Summer B., Goutman, Stephen A., Heiman-Patterson, Terry D., Hernandez, Dena G., Hoover, Ben, Jansson, Lilja, Kamel, Freya, Kirby, Janine, Kowall, Neil W., Laaksovirta, Hannu, Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, MacGowan, Daniel JL., Maragakis, Nicholas J., Mora, Gabriele, Mouzat, Kevin, Myllykangas, Liisa, Nalls, Mike A., Orrell, Richard W., Ostrow, Lyle W., Pamphlett, Roger, Pioro, Erik, Pulst, Stefan M., Ravits, John M., Renton, Alan E., Robberecht, Wim, Robey, Ian, Rogaeva, Ekaterina, Rothstein, Jeffrey D., Sendtner, Michael, Sidle, Katie C., Simmons, Zachary, Stone, David J., Tienari, Pentti J., Trojanowski, John Q., Troncoso, Juan C., Valori, Miko, Van Damme, Philip, Van Den Bosch, Ludo, Zinman, Lorne, Albani, Diego, Borroni, Barbara, Padovani, Alessandro, Bruni, Amalia, Clarimon, Jordi, Dols-Icardo, Oriol, Illán-Gala, Ignacio, Lleó, Alberto, Danek, Adrian, Galimberti, Daniela, Scarpini, Elio, Serpente, Maria, Graff, Caroline, Chiang, Huei-Hsin, Khoshnood, Behzad, Öijerstedt, Linn, Morris, Christopher M., Nacmias, Benedetta, Sorbi, Sandro, Nielsen, Jorgen E., Hjermind, Lynne E., Novelli, Valeria, Puca, Annibale A., Pastor, Pau, Alvarez, Ignacio, Diez-Fairen, Monica, Aguilar, Miquel, Perneczky, Robert, Diehl-Schimd, Janine, Rossi, Mina, Ruiz, Agustin, Boada, Mercè, Hernández, Isabel, Moreno-Grau, Sonia, Schlachetzki, Johannes C., Aarsland, Dag, Albert, Marilyn S., Attems, Johannes, Barrett, Matthew J., Beach, Thomas G., Bekris, Lynn M., Bennett, David A., Besser, Lilah M., Bigio, Eileen H., Black, Sandra E., Boeve, Bradley F., Bohannan, Ryan C., Brett, Francesca, Brunetti, Maura, Caraway, Chad A., Palma, Jose-Alberto, Calvo, Andrea, Canosa, Antonio, Dickson, Dennis, Duyckaerts, Charles, Faber, Kelley, Ferman, Tanis, Flanagan, Margaret E., Floris, Gianluca, Foroud, Tatiana M., Fortea, Juan, Gan-Or, Ziv, Gentleman, Steve, Ghetti, Bernardino, Gibbs, Jesse Raphael, Goate, Alison, Goldstein, David, González-Aramburu, Isabel, Graff-Radford, Neill R., Hodges, Angela K., Hu, Heng-Chen, Hupalo, Daniel, Infante, Jon, Iranzo, Alex, Kaiser, Scott M., Kaufmann, Horacio, Keith, Julia, Kim, Ronald C., Klein, Gregory, Krüger, Rejko, Kukull, Walter, Kuzma, Amanda, Lage, Carmen, Lesage, Suzanne, Leverenz, James B., Logroscino, Giancarlo, Lopez, Grisel, Love, Seth, Mao, Qinwen, Marti, Maria Jose, Martinez-McGrath, Elisa, Masellis, Mario, Masliah, Eliezer, May, Patrick, McKeith, Ian, Mesulam, Marek-Marsel, Monuki, Edwin S., Newell, Kathy L., Norcliffe-Kaufmann, Lucy, Palmer, Laura, Perkins, Matthew, Pletnikova, Olga, Molina-Porcel, Laura, Reynolds, Regina H., Rodríguez-Rodríguez, Eloy, Rohrer, Jonathan D., Sanchez-Juan, Pascual, Scherzer, Clemens R., Serrano, Geidy E., Shakkottai, Vikram, Sidransky, Ellen, Tayebi, Nahid, Thomas, Alan J., Tilley, Bension S., Walton, Ronald L., Woltjer, Randy, Wszolek, Zbigniew K., Xiromerisiou, Georgia, Zecca, Chiara, Phatnani, Hemali, Kwan, Justin, Sareen, Dhruv, Broach, James R., Arcila-Londono, Ximena, Lee, Edward B., Shneider, Neil A., Fraenkel, Ernest, Zaitlen, Noah, Berry, James D., Malaspina, Andrea, Cox, Gregory A., Thompson, Leslie M., Finkbeiner, Steve, Dardiotis, Efthimios, Miller, Timothy M., Chandran, Siddharthan, Pal, Suvankar, Hornstein, Eran, MacGowan, Daniel J., Heiman-Patterson, Terry, Hammell, Molly G., Patsopoulos, Nikolaos.A., Butovsky, Oleg, Dubnau, Joshua, Nath, Avindra, Harms, Matt, Aronica, Eleonora, Poss, Mary, Phillips-Cremins, Jennifer, Crary, John, Atassi, Nazem, Lange, Dale J., Adams, Darius J., Stefanis, Leonidas, Gotkine, Marc, Babu, Suma, Raj, Towfique, Paganoni, Sabrina, Shalem, Ophir, Smith, Colin, Zhang, Bin, Harris, Brent, Broce, Iris, Drory, Vivian, Ravits, John, McMillan, Corey, Menon, Vilas, Wu, Lani, Altschuler, Steven, Amar, Khaled, Archibald, Neil, Bandmann, Oliver, Capps, Erica, Church, Alistair, Coebergh, Jan, Costantini, Alyssa, Critchley, Peter, Ghosh, Boyd CP., Hu, Michele T.M., Kobylecki, Christopher, Leigh, P. Nigel, Mann, Carl, Massey, Luke A., Morris, Huw R., Nath, Uma, Pavese, Nicola, Paviour, Dominic, Sharma, Jagdish, Vaughan, Jenny, Dewan, Ramita, Chia, Ruth, Ding, Jinhui, Hickman, Richard A., Stein, Thor D., Abramzon, Yevgeniya, Ahmed, Sarah, Sabir, Marya S., Portley, Makayla K., Tucci, Arianna, Ibáñez, Kristina, Shankaracharya, F.N.U., Keagle, Pamela, Rossi, Giacomina, Caroppo, Paola, Tagliavini, Fabrizio, Waldo, Maria L., Johansson, Per M., Nilsson, Christer F., Rowe, James B., Benussi, Luisa, Binetti, Giuliano, Ghidoni, Roberta, Jabbari, Edwin, Viollet, Coralie, Glass, Jonathan D., Singleton, Andrew B., Silani, Vincenzo, Ross, Owen A., Ryten, Mina, Torkamani, Ali, Tanaka, Toshiko, Ferrucci, Luigi, Resnick, Susan M., Pickering-Brown, Stuart, Brady, Christopher B., Kowal, Neil, Hardy, John A., Van Deerlin, Vivianna, Vonsattel, Jean Paul, Harms, Matthew B., Ferrari, Raffaele, Landers, John E., Gibbs, J. Raphael, Dalgard, Clifton L., Scholz, Sonja W., and Traynor, Bryan J.

Published
2021
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15. Toward Precision Phenotyping of Multiple Sclerosis

Author

Pitt, David, Lo, Chih Hung, Gauthier, Susan A., Hickman, Richard A., Longbrake, Erin, Airas, Laura M., Mao-Draayer, Yang, Riley, Claire, De Jager, Philip Lawrence, Wesley, Sarah, Boster, Aaron, Topalli, Ilir, Bagnato, Francesca, Mansoor, Mohammad, Stuve, Olaf, Kister, Ilya, Pelletier, Daniel, Stathopoulos, Panos, Dutta, Ranjan, and Lincoln, Matthew R.

Published
2022
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16. Architecture and dynamics of the abscisic acid gene regulatory network.

Author

Aerts, Niels, Hickman, Richard, Van Dijken, Anja J.H., Kaufmann, Michael, Snoek, Basten L., Pieterse, Corné M.J., and Van Wees, Saskia C.M.

Subjects
*GENE regulatory networks, *TRANSCRIPTION factors, *PLANT hormones, *ABSCISIC acid, *GENETIC transcription
Abstract

SUMMARY: The plant hormone abscisic acid (ABA) regulates essential processes in plant development and responsiveness to abiotic and biotic stresses. ABA perception triggers a post‐translational signaling cascade that elicits the ABA gene regulatory network (GRN), encompassing hundreds of transcription factors (TFs) and thousands of transcribed genes. To further our knowledge of this GRN, we performed an RNA‐seq time series experiment consisting of 14 time points in the 16 h following a one‐time ABA treatment of 5‐week‐old Arabidopsis rosettes. During this time course, ABA rapidly changed transcription levels of 7151 genes, which were partitioned into 44 coexpressed modules that carry out diverse biological functions. We integrated our time‐series data with publicly available TF‐binding site data, motif data, and RNA‐seq data of plants inhibited in translation, and predicted (i) which TFs regulate the different coexpression clusters, (ii) which TFs contribute the most to target gene amplitude, (iii) timing of engagement of different TFs in the ABA GRN, and (iv) hierarchical position of TFs and their targets in the multi‐tiered ABA GRN. The ABA GRN was found to be highly interconnected and regulated at different amplitudes and timing by a wide variety of TFs, of which the bZIP family was most prominent, and upregulation of genes encompassed more TFs than downregulation. We validated our network models in silico with additional public TF‐binding site data and transcription data of selected TF mutants. Finally, using a drought assay we found that the Trihelix TF GT3a is likely an ABA‐induced positive regulator of drought tolerance. Significance Statement: The hormone abscisic acid (ABA) regulates many plant stress responses and plant development by activating a complex gene regulatory network. We unveiled key players and their hierarchy in the ABA network. For this, we generated high‐density RNA‐seq time series data of mature ABA‐treated Arabidopsis thaliana leaves and used existing and newly developed methods to integrate the transcriptional dynamics with publicly available TF‐binding data and RNA‐seq data of ABA‐treated plants inhibited in translation. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Liquid biopsy‐based circulating tumour (ct)DNA analysis of a spectrum of myeloid and lymphoid malignancies yields clinically actionable results

Author

Mata, Douglas A, primary, Lee, Jessica K, additional, Shanmugam, Vignesh, additional, Marcus, Chelsea B, additional, Schrock, Alexa B, additional, Williams, Erik A, additional, Ritterhouse, Lauren L, additional, Hickman, Richard A, additional, Janovitz, Tyler, additional, Patel, Nimesh R, additional, Kroger, Benjamin R, additional, Ross, Jeffrey S, additional, Mirza, Kamran M, additional, Oxnard, Geoffrey R, additional, Vergilio, Jo‐Anne, additional, Elvin, Julia A, additional, Benhamida, Jamal K, additional, Decker, Brennan, additional, and Xu, Mina L, additional

Published
2024
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19. Viscerality and Slowliness: An Anatomy of Artists' Pedagogies of Material and Time

Author

Denmead, Tyler and Hickman, Richard

Abstract

This paper explores community artists' pedagogies in relation to time and material. Thirteen unstructured interviews were conducted with eight artists under the auspices of an organisation that facilitated community-based workshops in Cambridgeshire, UK throughout 2011 and 2012. Concepts salient to the artists emerged, and six of the eight artists were observed facilitating twenty workshops across five sites. We found that the artists create conditions for open-ended enquiry across five dimensions: space, time, material, body, and language. This paper focuses on one of these dimensions--that of material, with reference to one other, that of time. We discuss artists' criteria for workshop materials, including simplicity, slippage, immediacy, richness, and ephemerality. We examine how the artists presented a "limited palette" of select materials, though provided each in abundance. And we interpret the artists using materials to facilitate what they described as slowliness--an immersive, pleasure state free from past prescription and future expectation.

Published
2012

20. Pituitary neuroendocrine tumors (PitNETs): nomenclature evolution, not clinical revolution

Author

Asa, Sylvia L., Asioli, Sofia, Bozkurt, Suheyla, Casar-Borota, Olivera, Chinezu, Laura, Comunoglu, Nil, Cossu, Giulia, Cusimano, Michael, Delgrange, Etienne, Earls, Peter, Ezzat, Shereen, Gazioglu, Nurperi, Grossman, Ashley, Guaraldi, Federica, Hickman, Richard A., Ikeda, Hidetoshi, Jaffrain-Rea, Marie-Lise, Karavitaki, Niki, Kraljević, Ivana, La Rosa, Stefano, Manojlović-Gačić, Emilija, Maartens, Niki, McCutcheon, Ian E., Messerer, Mahmoud, Mete, Ozgur, Nishioka, Hiroshi, Oz, Buge, Pakbaz, Sara, Pekmezci, Melike, Perry, Arie, Reiniger, Lilla, Roncaroli, Federico, Saeger, Wolfgang, Söylemezoğlu, Figen, Tachibana, Osamu, Trouillas, Jacqueline, Turchini, John, Uccella, Silvia, Villa, Chiara, Yamada, Shozo, and Yarman, Sema

Published
2020
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21. The Sabar Ways of Knowing: Sustainable Ideas towards Educational Ecology

Author

Hickman, Richard and Sinha, Pallawi

Abstract

In common conception, art is often confined to a painting, sculpture, architecture or performance; we maintain however that what enables any art or artistic practice to become aesthetic is human experience. Arts and aesthetic practices are integral to the everyday lives of the indigenous Sabar tribes of India, particularly, in ascertaining Sabar "ways of knowing, being and doing". This article describes the nature of Sabar aesthetic experience, and its educational relevance, through an empirical study employing ethnomethodology and innovative participatory tools. It examines definitions and identifies limitations considered through an indigenous lens before introducing the social actors of the study. Findings illustrates how aesthetic practices empower voice by enabling multitextual expressions, rebuilding trust with the community and generating data that other methods may render invisible. The article offers discussions on how everyday aesthetic experiences and practices are imperative to the development of an authentic being. It conceptualises an educational ecology towards the realisation of sustainable educational systems and culturally critical ideals of education. We argue for an education for emancipation, through difference not domination, through enabling aesthetic and authentic beings. Ultimately, we urge a critical and creative future citizenship that is empowered by education, not constrained by its demands.

Published
2018
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24. EPID-31. BRAIN TUMORS IN UNITED STATES MILITARY VETERANS

Author

Waite, Kristin, primary, Bihn, John, additional, Cioffi, Gino, additional, Neff, Corey, additional, Kruchko, Carol, additional, Ostrom, Quinn, additional, Swinnerton, Kaitlin, additional, Elbers, Danne, additional, Mooney, Michael A, additional, Rachlin, Jacob, additional, Stein, Thor, additional, Brophy, Mary, additional, Do, Nhan, additional, Priemer, David, additional, Perl, Daniel, additional, Ferguson, Ryan, additional, Hickman, Richard, additional, Nabors, Burt, additional, Rusiecki, Jennifer, additional, Barnholtz-Sloan, Jill, additional, and Fillmore, Nathanael, additional

Published
2023
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26. Transcriptional regulatory codes underlying Arabidopsis stress responses

Author

Hickman, Richard J.

Subjects
571.2, QK Botany
Abstract

Plant adaptation to stress is dependent upon the initialisation of molecular signalling networks that regulate the expression of stress-related genes. By examining high-resolution microarray datasets it has been possible to track gene expression changes over time during senescence and in response to infection by fungal pathogen Botrytis cineria in the model organism Arabidopsis thaliana. Dramatic variations in gene expression are observed at the onset of stress with different groups of genes showing different expression time-courses. This observation must, for a large part, be down to the action of different transcription factors (TFs) binding to the cis-regulatory DNA in the promoters of genes in each group and it is this regulatory code that underpins the gene regulatory networks that regulate stress responses. This thesis presents an interdisciplinary investigation of the regulatory codes that are responsible for controlling plant stress responses. Computational analysis of non-coding sequences provides a powerful approach to identify patterns within DNA that may function to regulate gene expression. This thesis covers the development of Analysis of Plant Promoter-Linked Elements (APPLES), an object-orientated software framework for the analysis of non-coding DNA. Within this environment, methods were developed to probe the regulatory codes that exist within these non-coding sequences and identify regulatory motifs that may function to regulate stress responses in Arabidopsis. APPLES methods were used to identify a novel motif that is likely to play a role in regulating drought responses in Arabidopsis, with experimental approaches providing support for this view. Using known motifs that describe previously characterised TF binding sites, it was possible to identify motifs that are associated with clusters of co-regulated genes identified from the senescence and Botrytis microarray time-course datasets. This analysis revealed cis-regulatory elements that may contribute to generating the observed expression patterns. In a contrasting approach to in silico identification of regulatory elements, the Yeast-1-Hybrid (Y1H) assay was used to experimentally identify interactions between TFs and non-coding DNA. The use of a TF library allowed the ability of approximately 1400 Arabidopsis TFs to interact with a given DNA sequence in a single assay. Using the stress-associated ANAC092 promoter as a test case, it was possible to use this highthroughput procedure to identify TFs that can bind to the promoter of this gene. This high-throughput Y1H system was then used to perform a detailed mapping of protein- DNA interactions that can occur across the core promoters of three highly related stress inducible TF-encoding genes, ANAC019, ANAC055 and ANAC072. Microarrays were used to assess the regulatory consequence of a subset of these interactions by perturbing the expression of interacting TFs and observing the effect on target gene expression during multiple stresses. This approach confirmed predicted regulatory relationships and therefore enhanced the current understanding of the transcriptional regulatory networks that operate during stress responses in Arabidopsis.

Published
2012

28. Multi-wavelength observations of cataclysmic variable stars

Author

Hickman, Richard D. G.

Subjects
520, QB Astronomy
Abstract

Observations of the cataclysmic variable systems EX Dra, Z Cha, and OY Car using multi-wavelength data ranging from near-infrared to X-ray bands are presented and analysed. Obscuration of the white dwarf by intervening material is discussed in context of all three systems, including the confirmation of iron lines in the spectrum of OY Car and the absorbing nature of the accretion disc upon the soft X-ray band in Z Cha. Evidence for spiral shocks and slingshot prominences from the secondary star are found in EX Dra, while the extent of Z Cha's boundary layer is probed with extensive modelling of simultaneous optical and X-ray data. Combined with a spectral analysis, this leads to the conclusion of a truncated inner disc present within the system. The first radial velocity measurement of OY Car's red secondary star is presented, and used to produce a fully spectroscopic determination of the system's mass ratio which is compared to previous attempts using the photometric method. The second part of this thesis deals with the improvement of the Ultracam and Ultraspec instruments. For the former, increased colour precision is achieved by careful calibration of the instrument's filter response with respect to the SDSS system; a charge modulation problem is investigated and quantified; and the development of a software system designed to improve observation and reduction workflow is detailed. For Ultraspec, a careful analysis of the CCD parameters is performed in order to prepare the instrument for scientific quality data publication, including an analysis of spurious charge found present. It is also shown that the AC coupling of the video circuit in the CCD can cause erroneous values in the readout but can be rectified, and presence of charge trailing caused by electron traps is investigated with preliminary corrections shown.

Published
2011

30. Architecture and Dynamics of the Jasmonic Acid Gene Regulatory Network

Author

Hickman, Richard, Van Verk, Marcel C., Van Dijken, Anja J.H., Mendes, Marciel Pereira, Vroegop-Vos, Irene A., Caarls, Lotte, Steenbergen, Merel, Van der Nagel, Ivo, Wesselink, Gert Jan, Jironkin, Aleksey, Talbot, Adam, Rhodes, Johanna, De Vries, Michel, Schuurink, Robert C., Denby, Katherine, Pieterse, Corné M.J., and Van Wees, Saskia C.M.

Published
2017

31. Brain tumors in United States military veterans

Author

Bihn, John R, primary, Cioffi, Gino, additional, Waite, Kristin A, additional, Kruchko, Carol, additional, Neff, Corey, additional, Price, Mackenzie, additional, Ostrom, Quinn T, additional, Swinnerton, Kaitlin N, additional, Elbers, Danne C, additional, Mooney, Michael A, additional, Rachlin, Jacob, additional, Stein, Thor D, additional, Brophy, Mary T, additional, Do, Nhan V, additional, Ferguson, Ryan E, additional, Priemer, David S, additional, Perl, Daniel P, additional, Hickman, Richard A, additional, Nabors, Burt, additional, Rusiecki, Jennifer, additional, Barnholtz-Sloan, Jill S, additional, and Fillmore, Nathanael R, additional

Published
2023
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32. Multi-OMIC analysis of Huntington disease reveals a neuroprotective astrocyte state

Author

Paryani, Fahad, primary, Kwon, Ji-Sun, additional, Ng, Chris W, additional, Madden, Nacoya, additional, Ofori, Kenneth, additional, Tang, Alice, additional, Lu, Hong, additional, Li, Juncheng, additional, Mahajan, Aayushi, additional, Davidson, Shawn M., additional, Basile, Anna, additional, McHugh, Caitlin, additional, Vonsattel, Jean Paul, additional, Hickman, Richard, additional, Zody, Michael, additional, Houseman, David E., additional, Goldman, James E., additional, Yoo, Andrew E., additional, Menon, Vilas, additional, and Al-Dalahmah, Osama, additional

Published
2023
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38. Brain tumors in United States military veterans.

Author

Bihn, John R, Cioffi, Gino, Waite, Kristin A, Kruchko, Carol, Neff, Corey, Price, Mackenzie, Ostrom, Quinn T, Swinnerton, Kaitlin N, Elbers, Danne C, Mooney, Michael A, Rachlin, Jacob, Stein, Thor D, Brophy, Mary T, Do, Nhan V, Ferguson, Ryan E, Priemer, David S, Perl, Daniel P, Hickman, Richard A, Nabors, Burt, and Rusiecki, Jennifer

Published
2024
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42. Identification of Lactuca sativa transcription factors impacting resistance to Botrytis cinerea through predictive network inference

Author

Pink, Harry, primary, Talbot, Adam, additional, Carter, Ryan, additional, Hickman, Richard, additional, Cooper, Oliver, additional, Law, Rebecca, additional, Higgins, Gilian, additional, Yao, Chenyi, additional, Gawthrop, Frances, additional, Hand, Paul, additional, Pink, David, additional, Clarkson, John, additional, and Denby, Katherine, additional

Published
2023
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45. Patterns of TDP ‐43 Deposition in Brains withLRRK2 G2019SMutations

Author

Agin‐Liebes, Julian, primary, Hickman, Richard A., additional, Vonsattel, Jean Paul, additional, Faust, Phyllis L., additional, Flowers, Xena, additional, Utkina Sosunova, Irina, additional, Ntiri, Joel, additional, Mayeux, Richard, additional, Surface, Matthew, additional, Marder, Karen, additional, Fahn, Stanley, additional, Przedborski, Serge, additional, and Alcalay, Roy N., additional

Published
2023
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46. Time-Series Transcriptomics Reveals That AGAMOUS-LIKE22 Affects Primary Metabolism and Developmental Processes in Drought-Stressed Arabidopsis

Author

Bechtold, Ulrike, Penfold, Christopher A., Jenkins, Dafyd J., Legaie, Roxane, Moore, Jonathan D., Lawson, Tracy, Matthews, Jack S.A., Vialet-Chabrand, Silvere R.M., Baxter, Laura, Subramaniam, Sunitha, Hickman, Richard, Florance, Hannah, Sambles, Christine, Salmon, Deborah L., Feil, Regina, Bowden, Laura, Hill, Claire, Baker, Neil R., Lunn, John E., Finkenstädt, Bärbel, Mead, Andrew, Buchanan-Wollaston, Vicky, Beynon, Jim, Rand, David A., Wild, David L., Denby, Katherine J., Ott, Sascha, Smirnoff, Nicholas, and Mullineaux, Philip M.

Published
2016

49. Huntington disease oligodendrocyte maturation deficits revealed by single-nucleus RNAseq are rescued by thiamine-biotin supplementation

Author

Massachusetts Institute of Technology. Department of Biological Engineering, Lim, Ryan G, Al-Dalahmah, Osama, Wu, Jie, Gold, Maxwell P, Reidling, Jack C, Tang, Guomei, Adam, Miriam, Dansu, David K, Park, Hye-Jin, Casaccia, Patrizia, Miramontes, Ricardo, Reyes-Ortiz, Andrea M, Lau, Alice, Hickman, Richard A, Khan, Fatima, Paryani, Fahad, Tang, Alice, Ofori, Kenneth, Miyoshi, Emily, Michael, Neethu, McClure, Nicolette, Flowers, Xena E, Vonsattel, Jean Paul, Davidson, Shawn, Menon, Vilas, Swarup, Vivek, Fraenkel, Ernest, Goldman, James E, Thompson, Leslie M, Massachusetts Institute of Technology. Department of Biological Engineering, Lim, Ryan G, Al-Dalahmah, Osama, Wu, Jie, Gold, Maxwell P, Reidling, Jack C, Tang, Guomei, Adam, Miriam, Dansu, David K, Park, Hye-Jin, Casaccia, Patrizia, Miramontes, Ricardo, Reyes-Ortiz, Andrea M, Lau, Alice, Hickman, Richard A, Khan, Fatima, Paryani, Fahad, Tang, Alice, Ofori, Kenneth, Miyoshi, Emily, Michael, Neethu, McClure, Nicolette, Flowers, Xena E, Vonsattel, Jean Paul, Davidson, Shawn, Menon, Vilas, Swarup, Vivek, Fraenkel, Ernest, Goldman, James E, and Thompson, Leslie M

Abstract

AbstractThe complexity of affected brain regions and cell types is a challenge for Huntington’s disease (HD) treatment. Here we use single nucleus RNA sequencing to investigate molecular pathology in the cortex and striatum from R6/2 mice and human HD post-mortem tissue. We identify cell type-specific and -agnostic signatures suggesting oligodendrocytes (OLs) and oligodendrocyte precursors (OPCs) are arrested in intermediate maturation states. OL-lineage regulators OLIG1 and OLIG2 are negatively correlated with CAG length in human OPCs, and ATACseq analysis of HD mouse NeuN-negative cells shows decreased accessibility regulated by OL maturation genes. The data implicates glucose and lipid metabolism in abnormal cell maturation and identify PRKCE and Thiamine Pyrophosphokinase 1 (TPK1) as central genes. Thiamine/biotin treatment of R6/1 HD mice to compensate for TPK1 dysregulation restores OL maturation and rescues neuronal pathology. Our insights into HD OL pathology spans multiple brain regions and link OL maturation deficits to abnormal thiamine metabolism.

Published
2023

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