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1. Impact of BCR::ABL1 single nucleotide variants on asciminib efficacy

Author

Innes, Andrew J., Hayden, Chloe, Orovboni, Victoria, Claudiani, Simone, Fernando, Fiona, Khan, Afzal, Rees, David, Byrne, Jennifer, Gallipoli, Paolo, Francis, Sebastian, Copland, Mhairi, Horne, Gillian, Raghavan, Manoj, Arnold, Claire, Collins, Angela, Cranfield, Tanya, Cunningham, Nicholas, Danga, Akila, Forsyth, Peter, Frewin, Rebecca, Garland, Paula, Hannah, Guy, Avenoso, Daniele, Hassan, Sandra, Huntly, Brian J. P., Husain, Jissan, Makkuni, Sudhakaran, Rothwell, Kate, Khorashad, Jamshid, Apperley, Jane F., and Milojkovic, Dragana

Published
2024
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3. RISING TOGETHER IN RESPONSE TO THE COVID-19 PANDEMIC

Author

Kaczor, Keri, Alegado, Rosanna ‘Anolani, Hintzen, Katy, Ching, Lauren, Lieberman, Michael, Chang, Sandra, Nakano, Eileen, Sy, Angela, Horio, David, Tam, Kaeo, Nerurkar, Vivek R., Smyth, Ashley, Collins, Angela, Fallon, Kathleen, Focazio, Paul, and Kreisler, Samantha

Published
2024

4. Outcomes with single-agent gilteritinib for relapsed or refractory FLT3-mutant AML after contemporary induction therapy

Author

Othman, Jad, Hwang, Angela, Brodermann, Maximillian, Abdallah, Islam, McCloskey, Kayleigh, Gallipoli, Paolo, Clarke, Georgina, Dang, Raymond, Vidler, Jennifer, Krishnamurthy, Pramila, Basheer, Faisal, Latif, Anne-Louise, Palanicawandar, Renuka, Taylor, Tom, Khan, Asra, Campbell, Victoria, Hogan, Francesca, Kanellopoulos, Alex, Fleming, Kathryn, Collins, Angela, Dalley, Chris, Loke, Justin, Marshall, Scott, Taussig, David, Munisamy, Sreetharan, Loizou, Eleana, Yassin, Heba, Dennis, Mike, Zhao, Rui, Belsham, Edward, Murray, Duncan, Fowler, Nicole, O'Nions, Jenny, Khan, Anjum, Sellar, Rob, and Dillon, Richard

Published
2024
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5. Real-world outcomes of newly diagnosed AML treated with venetoclax and azacitidine or low-dose cytarabine in the UK NHS

Author

Othman, Jad, Lam, Ho Pui Jeff, Leong, Sarah, Basheer, Faisal, Abdallah, Islam, Fleming, Kathryn, Mehta, Priyanka, Yassin, Heba, Laurie, John, Austin, Michael, Gallipoli, Paolo, Taylor, Tom, Dennis, Mike, Elliot, Johnathon, Clarke, Georgina, Dang, Raymond, Vidler, Jennifer, Krishnamurthy, Pramila, Latif, Anne-Louise, Kalkur, Pallavi, Shahidianakbar, Maryam, Campbell, Victoria, Mannari, Deepak, Sutherland, Emily, Wickramaratne, Thishakya, Collins, Angela, Zhao, Rui, Mak, Herng, Belsham, Edward, Banerjee, Shabnam, Bashir, Jamila, Pillai, Srinivas, Whitmill, Richard, Galli, Sofia, Amer, Mariam, Murthy, Vidhya, Murray, Duncan, Wandroo, Farooq, Hogan, Francesca, Crolla, Francesca, Fowler, Nicole, Khan, Anjum, O’Nions, Jenny, and Dillon, Richard

Published
2024
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7. Real-world study of children and young adults with myeloproliferative neoplasms: identifying risks and unmet needs

Author

Sobas, Marta, Kiladjian, Jean-Jacques, Beauverd, Yan, Curto-Garcia, Natalia, Sadjadian, Parvis, Shih, Lee Yung, Devos, Timothy, Krochmalczyk, Dorota, Galli, Serena, Bieniaszewska, Maria, Seferynska, Ilona, McMullin, Mary Frances, Armatys, Anna, Spalek, Adrianna, Waclaw, Joanna, Zdrenghea, Mihnea, Legros, Laurence, Girodon, François, Lewandowski, Krzysztof, Angona Figueras, Anna, Samuelsson, Jan, Abuin Blanco, Aitor, Cony-Makhoul, Pascale, Collins, Angela, James, Chloé, Kusec, Rajko, Lauermannova, Marie, Noya, Maria Sol, Skowronek, Malgorzata, Szukalski, Lukasz, Szmigielska-Kaplon, Anna, Wondergem, Marielle, Dudchenko, Iryna, Gora Tybor, Joanna, Laribi, Kamel, Kulikowska de Nalecz, Anna, Demory, Jean-Loup, Le Du, Katell, Zweegman, Sonja, Besses Raebel, Carlos, Skoda, Radek, Giraudier, Stéphane, Griesshammer, Martin, Harrison, Claire N., and Ianotto, Jean-Christophe

Published
2022
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8. PembroWM: A phase II trial to investigate the safety and efficacy of rituximab and pembrolizumab in relapsed/refractory Waldenström's Macroglobulinaemia.

Author

Kothari, Jaimal, Eyre, Toby, Rismani, Ali, Ediriwickrema, Kushani, Edwards, Darren, Galani, Sevasti, Wilson, William, Lawrie, Anthony, Clifton‐Hadley, Laura, McCarthy, Helen, Collins, Angela, Lewis, David, Arulogan, Suzanne, Auer, Rebecca, Pratt, Guy, de Tute, Ruth, Owen, Roger, and D'Sa, Shirley

Subjects
BRUTON tyrosine kinase, PROTEIN-tyrosine kinase inhibitors, OVERALL survival, SURVIVAL rate, THERAPEUTICS
Abstract

Summary: The optimal therapeutic approach for relapsed/refractory (R/R) Waldenström's Macroglobulinaemia (WM) has not been clearly defined, especially after treatment with chemoimmunotherapy (CIT) and covalent Bruton's tyrosine kinase inhibitors (cBTKi). The PembroWM trial is a multi‐centre, phase II, single‐arm study assessing the safety, tolerability and efficacy of rituximab with pembrolizumab in R/R WM patients who had received at least one prior line of treatment, with all having relapsed post‐CIT and most also exposed to cBTKi. A total of 17 patients were enrolled, with a median age of 70, and median of three prior lines of therapy with 15 either refractory or intolerant of a cBTKi. A significant proportion was identified as genomically high risk with BTKC481, CXCR4 and MYD88 L265P wild‐type aberrations. Twenty‐four‐week overall response rate was 50% (60% CI 39.3%–60.7%), and median duration of response was 11.6 months (IQR: 6.3–17). The median progression‐free survival was 13.6 months (95% CI 3–19.8), and the median overall survival (OS) was not reached. Treatment was well tolerated, with minimal numbers of immune‐mediated AEs typically seen with checkpoint inhibitors. PembroWM is the first study to evaluate the feasibility of PD‐1 axis modulation in WM and has shown that in combination with Rituximab the combination is safe and deliverable. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Regional-scale variability in the movement ecology of marine fishes revealed by an integrative acoustic tracking network

Author

Friess, Claudia, Lowerre-Barbieri, Susan K., Poulakis, Gregg R., Hammerschlag, Neil, Gardiner, Jayne M., Kroetz, Andrea M., Bassos-Hull, Kim, Bickford, Joel, Bohaboy, Erin C., Ellis, Robert D., Menendez, Hayden, Patterson, William F., Price, Melissa E., Rehage, Jennifer S., Shea, Colin P., Smukall, Matthew J., Burnsed, Sarah Walters, Wilkinson, Krystan A., Young, Joy, Collins, Angela B., DeGroot, Breanna C., Peterson, Cheston T., Purtlebaugh, Caleb, Randall, Michael, Scharer, Rachel M., Schloesser, Ryan W., Wiley, Tonya R., Alvarez, Gina A., Danylchuk, Andy J., Fox, Adam G., Grubbs, R. Dean, Hill, Ashley, Locascio, James V., O’Donnell, Patrick M., Skomal, Gregory B., Whoriskey, Fred G., and Griffin, Lucas P.

Published
2021

15. Advanced Hodgkin lymphoma in the East of England: a 10-year comparative analysis of outcomes for real-world patients treated with ABVD or escalated-BEACOPP, aged less than 60 years, compared with 5-year extended follow-up from the RATHL trial

Author

Russell, James, Collins, Angela, Fowler, Alexis, Karanth, Mamatha, Saha, Chandan, Docherty, Suzanne, Padayatty, Joseph, Maw, Kyaw, Lentell, Isabel, Cooke, Lisa, Hodson, Andrew, Shah, Nimish, Sadullah, Shalal, Grigoropoulos, Nicholas, Qian, Wendi, Kirkwood, Amy A., Uttenthal, Benjamin J., Johnson, Peter, and Follows, George A.

Published
2021
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18. Impact of BCR::ABL1single nucleotide variants on asciminib efficacy

Author

Innes, Andrew J., Hayden, Chloe, Orovboni, Victoria, Claudiani, Simone, Fernando, Fiona, Khan, Afzal, Rees, David, Byrne, Jennifer, Gallipoli, Paolo, Francis, Sebastian, Copland, Mhairi, Horne, Gillian, Raghavan, Manoj, Arnold, Claire, Collins, Angela, Cranfield, Tanya, Cunningham, Nicholas, Danga, Akila, Forsyth, Peter, Frewin, Rebecca, Garland, Paula, Hannah, Guy, Avenoso, Daniele, Hassan, Sandra, Huntly, Brian J. P., Husain, Jissan, Makkuni, Sudhakaran, Rothwell, Kate, Khorashad, Jamshid, Apperley, Jane F., and Milojkovic, Dragana

Abstract

Asciminib is a potent and selective inhibitor of BCR::ABL1, with potential to avoid toxicity resulting from off-target kinase inhibition. Forty-nine patients treated with asciminib under a managed access program in the UK were evaluated for toxicity and response. Intolerance, rather than resistance (65% vs. 35%), was the most common reason for cessation of the last-line of treatment but asciminib was well tolerated, with most patients (29, 59%) remaining on treatment at a median of 14 months follow-up, and only 6 (12%) stopping for intolerance. Of 44 patients assessable for response, 29 (66%) achieved a complete cytogenetic response (CCyR) or better, with poorer responses seen in those stopping their last-line of therapy for resistance. Fewer patients with a prior history of a non-T315I-BCR::ABL1single nucleotide variant (BSNV), or a non-T315I-BSNV detectable at baseline achieved CCyR. Serial tracking of BSNV by next generation sequencing demonstrated clonal expansion of BSNV-harbouring populations, which in some settings was associated with resistance (E459K, F317L, F359I), while in others was seen in the context of ongoing response, often with intensified dosing (T315I, I502F). These data suggest that asciminib exerts selective pressure on some BSNV-harbouring populations in vivo, some of which may respond to intensified dosing.

Published
2024
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20. Embedded Spreadsheet Modelling

Author

Collins, Angela

Subjects
Computer Science - Human-Computer Interaction
Abstract

In larger accounting firms, specialist modellers typically sit in separate teams. This paper will look at the advantages of embedding a specialist modeller within a Corporate Finance Team., Comment: 5 Pages

Published
2009

22. Juvenile Waivers as a Mechanism in the Erosion of the Juvenile Justice System.

Author

Collins, Angela M. and Cooper, Maisha

Subjects
*JUVENILE justice administration, *CRIMINAL courts, *WAIVER, *EROSION, *JUVENILE delinquency, *JUVENILE offenders, *ADULTS
Abstract

This paper discusses how juvenile waiver policies may be leading to a reduction in the rehabilitative nature of the juvenile justice system. The first section discusses the value of the juvenile justice system. Here, the beginning of the juvenile justice system and why the juvenile justice system is important will be summarized. The second section explains the movement that is being made toward a more punitive approach in regard to juvenile delinquents and how this could lead to the erosion of the juvenile justice system. Next is a discussion of how waivers play a part in the erosion and how their continued use could prove very dangerous for the juvenile justice system. The next section will look at the implications of the erosion and what could potentially happen if we lost the juvenile system. Last, there will be a glance at possibilities for the future, along with suggestions on how to improve the use of waivers. Overall, this paper will show that the use of juvenile waivers may be leading the United States away from a rehabilitative system for juveniles to a smaller version of an adult criminal court. [ABSTRACT FROM AUTHOR]

Published
2024
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31. Forced Expiratory Volume in 1 Second Variability Helps Identify Patients with Cystic Fibrosis at Risk of Greater Loss of Lung Function

Author

Morgan, Wayne, Konstan, Michael, Liou, Ted, McColley, Susanna, McMullen, Ann, Quittner, Alexandra, Regelmann, Warren, Ren, Clement, Rosenfeld, Margaret, Sawicki, Greg, Schechter, Michael, VanDevanter, Donald, Wagener, Jeffrey, Woo, Marlyn, Brasfield, Dana, Lyrene, Raymond, Sindel, Lawrence, Roberts, Dion, Carroll, John, Warren, Robert, Nassri, Louay, Anderson, Paula, Brown, Mark, Silverthorn, Amy, Radford, Peggy, Gong, Gerald, Legris, Gregory, Greene, Gerald, Sudhakar, Reddivalam, Platzker, Arnold, Nickerson, Bruce, Hardy, Karen, Harwood, Ivan, Shay, Gregory, Quick, Bryon, Lieberthal, Allan, Moss, Richard, Landon, Chris, Fanous, Yvonne, Lieberman, Jay, Spiritus, Eugene, Chipps, Bradley, McDonald, Ruth, Pian, Mark, Cropp, Gerd, Lewis, Nancy, Nielson, Dennis, Shapiro, Bertrand, Wagener, Jeff, Accurso, Frank, Saavedra, Milene, Daigle, Karen, Hen, Jacob, Palazzo, Regina, Dodds, Kathryn, Pad-man, Raj, Goodill, John, Winnie, Glenna, Davies, Lea, Kriseman, Tony, Sallent, Jorge, Chiaro, Joseph, Kubiet, Martin, Goldfinger, Sue, Schwartzman, Morton, Diaz, Carlosenrique, Maupin, Kevin, Riff, Eduardo, Geller, David, Livingston, Floyd, Mavunda, Kunjana, Birriel, Jose, Jr., Faverio, Luis, Rosenberg, David, Schaeffer, David, Sherman, James, Wagner, Mary, Light, Michael, Schnapf, Bruce, Montgomery, Gary, Kirchner, Kevin, Weatherly, Mark, Caplan, Daniel, Guill, Margaret, Hudson, Valera, Akhter, Javeed, Davison, Donald, Boas, Steven, Chung, Youngran, Latner, Rennee, Aljadeff, Gabriel, Chan, Youngran, Kraut, Jerome, Stone, Arvey, Still, John Lloyd, Sharma, Girish, Eagleton, Lanie, Hopkins, Patricia, Chatrath, Umesh, Lester, Lucille, Kim, Young-Jee, Anthony, Veena, Eigan, Howard, Howenstine, Michelle, James, Pushpom, Gergesha, Edward, Harris, James, Plant, Robert, Zivkovich, Veljko, Collins, Angela, Nassif, Edward, Ahrens, Richard, Doornbos, Daniel, Kanarek, Joseph, Leff, Richard, Shaw, Pamela, Demoss, Elanor, Riva, Maria, Sullivan, Leonard, Anstead, Michael, Kanga, Jamshed, Eid, Nemr, Morton, Ron, Hilman, Bettina, Jones, Kim, Davis, Scott, Harder, Ralph, Lever, Tom, Cairns, Anne Marie, Caldwell, Edgar, Zuckerman, Jonathan, Mogayzel, Peter, Rosenstein, Beryl, McQuestion, John, Perry, Donna, Rosenberg, Samuel, Gerstle, Robert, Colin, Andrew, Wohl, Mary Ellen, Lapey, Allan, Yee, William, O'Sullivan, Brian, Zwerdling, Robert, Abdulhamid, Ibrahim, O'Hagan, Adrian, Schuen, John, Kurlandsky, Lawrence, Honicky, Richard, Homnick, Douglas, Marks, John, Pichurko, Bohdan, Maxvold, Norma, Nasr, Samya, Simon, Richard, Tsai, Wan, Kissner, Dana, McNamara, John, Henry, Nancy, Marker, Stephen, Pryor, Michael, Walker, Lynn, Woodward, Jim, Mizell, Louis, Miller, Suzanne, Rosenbluth, Daniel, Black, Philip, McCubbin, Michael, Cohen, Alan, Ferkol, Thomas, Mallory, George, Rejent, Anthony, Rubin, Bruce, Graff, Gavin, Konig, Peter, Colombo, John, Murphy, Peter, Boyle, William, Parker, Worth, Patton, Chandler, Zanni, Robert, Atlas, Arthur, Turcios, Nelson, Laraya-Cuasay, Lourdes, Bisberg, Dorothy, Aguila, Helen, Allen, Sarah, James, David, Perkett, Elizabeth, Thompson, Marsha, Budhecha, Sonia, Diaz, Ruben, Rosen, Jonathan, Kaslovsky, Robert, Percciacante, Ronald, Borowitz, Drucy, Cronin, Joseph, McMahon, Colin, Quittell, Lynne, Giusti, Robert, Cohen, Rubin, DeCelie-Germana, Joan, Gorvoy, Jack, Patel, Kalpan, Kattan, Meyer, Dozor, Allen, DiMango, Emily, Berdella, Maria, Anbar, Ran, Ianuzzi, Debra, Sexton, James, Tayag-Kier, Catherine, McBride, John, Voter, Karen, Dimaio, Mary, Georgitis, John, Majure, Joseph Marc, Martinez, Maria, McIntosh, Clarke, Leigh, Margaret, Black, Hugh, Hughes, James, Kantak, Anand, Wilmott, Robert, Omlor, Gregory, Stone, Robert, McCoy, Karen, Acton, James, Doershuk, Carl, Fink, Robert, Steffan, Michael, Vauthy, Pierre, Joseph, Patricia, Reyes, Santiago, Kramer, John, Royall, James, Eisenberg, Jay, Wall, Michael, Fiel, Stanley, Scanlin, Thomas, Phadke, Shroti, Weinberg, Joel, Sexauer, William, Wolf, Stephen, Holsclaw, Douglas, Klein, Debra, Warren, Stuart, Kinsey, Robert, Perez, Carlos, Ganeshanathan, Muttiah, Shinnick, James, Panitch, Howard, Varlotta, Laurie, Robinson, Cynthia, Santana, Jose Rodriguez, Passero, Mary Ann, Gwinn, Jane, Baker, Robert, Bowman, Michael, Flume, Patrick, Brown, Daniel, Marville, Roxanne, Wallace, James, Parry, Rodney, Ellenburg, Don, Rogers, John, Mohon, Ricky, Ledbetter, Joel, Hanissian, Aram, Schoumacher, Robert, Campbell, Preston, Harris, Christopher, Slovis, Bonnie, Stokes, Dennis, Hale, Kathryn, Katz, Marcia, Seilheimer, Dan, Sockrider, Marianne, Frank, Allan, Daniel, James, Cunningham, James, Browning, Iley, Bray, John, Dove, Amanda, Mandujano, Fernando, Tremper, Larry, Morse, Martha, Willey-Courand, Donna, Copenhaver, Steven, Pohl, John, McWilliams, Bennie, Martine-Logvinoff, Marie, Wallace, Marsh, Klein, Robert, Amaro, Rodolfo, Couch, Leslie, Brown, Michael, Prestidge, Claude, Inscore, Stephen, Lipton, Andrew, Chatfield, Barbara, Liou, Theodore, Marshall, Bruce, Lahiri, Thomas, Swartz, Donald, Whittaker, Laurie, Karlson, Karl, Ropoll, Ignacio, Rubio, Thomas, Schmidt, Joel, Thomas, David, Osborn, John, Froh, Deborah, Gaston, Benjamin, Elliott, Greg, Gibson, Ronald, Ramsey, Bonnie, McCarthy, Michael, Larson, Lawrence, Ricker, David, Robbins, Mark, Aitken, Moira, Emerson, Julia, Aronoff, Stephen, Moffett, Kathryn, Biller, Julie, Splaingard, Mark, Sullivan, Bradley, Pritchard, Paul, Adair, Stu, Holzwarth, Peter, Dopico, Guillermo, Meyer, Keith, Green, Christopher, Rock, Michael, Morgan, Wayne J., VanDevanter, Donald R., Pasta, David J., Foreman, Aimee J., Wagener, Jeffrey S., and Konstan, Michael W.

Published
2016
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36. Real-World Experience of Asciminib: Factors Associated with Response

Author

Innes, Andrew J., primary, Hayden, Chloe, additional, Orovboni, Victoria, additional, Rees, David, additional, Claudiani, Simone, additional, Fernando, Fiona, additional, Khan, Afzal, additional, Byrne, Jennifer, additional, Gallipoli, Paolo, additional, Francis, Sebastian, additional, Copland, Mhairi, additional, Horne, Gillian, additional, Raghavan, Manoj, additional, Arnold, Claire, additional, Collins, Angela, additional, Cranfield, Tanya, additional, Cunningham, Nicholas, additional, Danga, Akila, additional, Forsyth, Peter, additional, Frewin, Rebecca, additional, Garland, Paula, additional, Hannah, Guy, additional, Hassan, Sandra, additional, Huntly, Brian James Patrick, additional, Husain, Jissan, additional, Makkuni, Sudhakaran, additional, Rothwell, Kate, additional, Foroni, Letizia, additional, Apperley, Jane F., additional, and Milojkovic, Dragana, additional

Published
2022
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37. Pembrowm: Results of a Multi-Centre Phase II Trial Investigating the Safety and Efficacy of Rituximab and Pembrolizumab in Relapsed/Refractory Waldenström's Macroglobulinaemia

Author

Kothari, Jaimal, primary, Eyre, Toby A., additional, Rismani, Ali, additional, McCarthy, Helen, additional, Collins, Angela, additional, Lewis, David John, additional, Arulogun, Suzanne O, additional, Wilson, William, additional, Clifton-Hadley, Laura, additional, Edwards, Darren, additional, Ediriwickrema, Kushani, additional, Auer, Rebecca, additional, Pratt, Guy, additional, de Tute, Ruth M., additional, Owen, Roger G, additional, and D'Sa, Shirley, additional

Published
2022
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42. A Randomized Clinical Trial of Acceptance and Commitment Therapy versus Progressive Relaxation Training for Obsessive-Compulsive Disorder

Author

Twohig, Michael P., Hayes, Steven C., Plumb, Jennifer C., Pruitt, Larry D., Collins, Angela B., Hazlett-Stevens, Holly, and Woidneck, Michelle R.

Abstract

Objective: Effective treatments for obsessive-compulsive disorder (OCD) exist, but additional treatment options are needed. The effectiveness of 8 sessions of acceptance and commitment therapy (ACT) for adult OCD was compared with progressive relaxation training (PRT). Method: Seventy-nine adults (61% female) diagnosed with OCD (mean age = 37 years; 89% Caucasian) participated in a randomized clinical trial of 8 sessions of ACT or PRT with no in-session exposure. The following assessments were completed at pretreatment, posttreatment, and 3-month follow-up by an assessor who was unaware of treatment conditions: Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Beck Depression Inventory-II, Quality of Life Scale, Acceptance and Action Questionnaire, Thought Action Fusion Scale, and Thought Control Questionnaire. Treatment Evaluation Inventory was completed at posttreatment. Results: ACT produced greater changes at posttreatment and follow-up over PRT on OCD severity (Y-BOCS: ACT pretreatment = 24.22, posttreatment = 12.76, follow-up = 11.79; PRT pretreatment = 25.4, posttreatment = 18.67, follow-up = 16.23) and produced greater change on depression among those reporting at least mild depression before treatment. Clinically significant change in OCD severity occurred more in the ACT condition than PRT (clinical response rates: ACT posttreatment = 46%-56%, follow-up = 46%-66%; PRT posttreatment = 13%-18%, follow-up = 16%-18%). Quality of life improved in both conditions but was marginally in favor of ACT at posttreatment. Treatment refusal (2.4% ACT, 7.8% PRT) and dropout (9.8% ACT, 13.2% PRT) were low in both conditions. Conclusions: ACT is worth exploring as a treatment for OCD. (Contains 1 table, 2 figures and 1 footnote.)

Published
2010
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43. Genetically determined population structure of hogfish (Labridae: Lachnolaimus maximus) in the southeastern United States

Author

Seyoum, Seifu, Collins, Angela B., Puchulutegui, Cecilia, McBride, Richard S., and Tringali, Michael D.

Subjects
Fish populations -- Genetic aspects -- Distribution, Company distribution practices, Zoology and wildlife conservation
Abstract

Abstract--Hogfish (Labridae: Lachnolaimus maximus) is distributed across several biogeographic regions, but its stock structure has been poorly documented, confounding stock assessment and management of this reef fishery species. In this [...]

Published
2015
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49. The ubiquitin ligase parkin mediates resistance to intracellular pathogens

Author

Manzanillo, Paolo S., Ayres, Janelle S., Watson, Robert O., Collins, Angela C., Souza, Gianne, Rae, Chris S., Schneider, David S., Nakamura, Ken, Shiloh, Michael U., and Cox, Jeffery S.

Subjects
Physiological aspects, Research, Health aspects, Ubiquitin -- Physiological aspects -- Research, Pathogenic microorganisms -- Health aspects -- Research, Ligases -- Physiological aspects -- Research
Abstract

Eukaryotic cells target invading microbes to autophagosomes through a process termed xenophagy, which has a key role in innate immune defence. Various intracellular bacterial pathogens, including Mycobacterium tuberculosis, are targeted [...], Ubiquitin-mediated targeting of intracellular bacteria to the autophagy pathway is a key innate defence mechanism against invading microbes, including the important human pathogen Mycobacterium tuberculosis. However, the ubiquitin ligases responsible for catalysing ubiquitin chains that surround intracellular bacteria are poorly understood. The parkin protein is a ubiquitin ligase with a well-established role in mitophagy, and mutations in the parkin gene (PARK2) lead to increased susceptibility to Parkinson's disease. Surprisingly, genetic polymorphisms in the PARK2 regulatory region are also associated with increased susceptibility to intracellular bacterial pathogens in humans, including Mycobacterium leprae and Salmonella enterica serovar Typhi, but the function of parkin in immunity has remained unexplored. Here we show that parkin has a role in ubiquitin-mediated autophagy of M. tuberculosis. Both parkin-deficient mice and flies are sensitive to various intracellular bacterial infections, indicating parkin has a conserved role in metazoan innate defence. Moreover, our work reveals an unexpected functional link between mitophagy and infectious disease.

Published
2013
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