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1. How Biophysical Forces Regulate Human B Cell Lymphomas

Author

F. Apoorva, Alexander M. Loiben, Shivem B. Shah, Alberto Purwada, Lorena Fontan, Rebecca Goldstein, Brian J. Kirby, Ari M. Melnick, Benjamin D. Cosgrove, and Ankur Singh

Subjects
Biology (General), QH301-705.5
Abstract

Summary: The role of microenvironment-mediated biophysical forces in human lymphomas remains elusive. Diffuse large B cell lymphomas (DLBCLs) are heterogeneous tumors, which originate from highly proliferative germinal center B cells. These tumors, their associated neo-vessels, and lymphatics presumably expose cells to particular fluid flow and survival signals. Here, we show that fluid flow enhances proliferation and modulates response of DLBCLs to specific therapeutic agents. Fluid flow upregulates surface expression of B cell receptors (BCRs) and integrin receptors in subsets of ABC-DLBCLs with either CD79A/B mutations or WT BCRs, similar to what is observed with xenografted human tumors in mice. Fluid flow differentially upregulates signaling targets, such as SYK and p70S6K, in ABC-DLBCLs. By selective knockdown of CD79B and inhibition of signaling targets, we provide mechanistic insights into how fluid flow mechanomodulates BCRs and integrins in ABC-DLBCLs. These findings redefine microenvironment factors that regulate lymphoma-drug interactions and will be critical for testing targeted therapies. : Apoorva et al. report a lymphoma micro-reactor to understand biophysical factors that regulate lymphoma growth and their therapeutic responses. They describe the role of fluid forces, from lymphatics and neo-vessels, in mechanomodulation of integrin and B cell receptor signaling. These insights shed light on the heterogeneous nature of lymphomas and may allow faster translation of therapeutics. Keywords: signaling, chemotherapy, B cell receptor, fluid, shear stress, mutation, integrin, mechanomodulation, lymph node, lymphatics

Published
2018
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2. Expanding the diversity of mycobacteriophages: insights into genome architecture and evolution.

Author

Welkin H Pope, Deborah Jacobs-Sera, Daniel A Russell, Craig L Peebles, Zein Al-Atrache, Turi A Alcoser, Lisa M Alexander, Matthew B Alfano, Samantha T Alford, Nichols E Amy, Marie D Anderson, Alexander G Anderson, Andrew A S Ang, Manuel Ares, Amanda J Barber, Lucia P Barker, Jonathan M Barrett, William D Barshop, Cynthia M Bauerle, Ian M Bayles, Katherine L Belfield, Aaron A Best, Agustin Borjon, Charles A Bowman, Christine A Boyer, Kevin W Bradley, Victoria A Bradley, Lauren N Broadway, Keshav Budwal, Kayla N Busby, Ian W Campbell, Anne M Campbell, Alyssa Carey, Steven M Caruso, Rebekah D Chew, Chelsea L Cockburn, Lianne B Cohen, Jeffrey M Corajod, Steven G Cresawn, Kimberly R Davis, Lisa Deng, Dee R Denver, Breyon R Dixon, Sahrish Ekram, Sarah C R Elgin, Angela E Engelsen, Belle E V English, Marcella L Erb, Crystal Estrada, Laura Z Filliger, Ann M Findley, Lauren Forbes, Mark H Forsyth, Tyler M Fox, Melissa J Fritz, Roberto Garcia, Zindzi D George, Anne E Georges, Christopher R Gissendanner, Shannon Goff, Rebecca Goldstein, Kobie C Gordon, Russell D Green, Stephanie L Guerra, Krysta R Guiney-Olsen, Bridget G Guiza, Leila Haghighat, Garrett V Hagopian, Catherine J Harmon, Jeremy S Harmson, Grant A Hartzog, Samuel E Harvey, Siping He, Kevin J He, Kaitlin E Healy, Ellen R Higinbotham, Erin N Hildebrandt, Jason H Ho, Gina M Hogan, Victoria G Hohenstein, Nathan A Holz, Vincent J Huang, Ericka L Hufford, Peter M Hynes, Arrykka S Jackson, Erica C Jansen, Jonathan Jarvik, Paul G Jasinto, Tuajuanda C Jordan, Tomas Kasza, Murray A Katelyn, Jessica S Kelsey, Larisa A Kerrigan, Daryl Khaw, Junghee Kim, Justin Z Knutter, Ching-Chung Ko, Gail V Larkin, Jennifer R Laroche, Asma Latif, Kohana D Leuba, Sequoia I Leuba, Lynn O Lewis, Kathryn E Loesser-Casey, Courtney A Long, A Javier Lopez, Nicholas Lowery, Tina Q Lu, Victor Mac, Isaac R Masters, Jazmyn J McCloud, Molly J McDonough, Andrew J Medenbach, Anjali Menon, Rachel Miller, Brandon K Morgan, Patrick C Ng, Elvis Nguyen, Katrina T Nguyen, Emilie T Nguyen, Kaylee M Nicholson, Lindsay A Parnell, Caitlin E Peirce, Allison M Perz, Luke J Peterson, Rachel E Pferdehirt, Seegren V Philip, Kit Pogliano, Joe Pogliano, Tamsen Polley, Erica J Puopolo, Hannah S Rabinowitz, Michael J Resiss, Corwin N Rhyan, Yetta M Robinson, Lauren L Rodriguez, Andrew C Rose, Jeffrey D Rubin, Jessica A Ruby, Margaret S Saha, James W Sandoz, Judith Savitskaya, Dale J Schipper, Christine E Schnitzler, Amanda R Schott, J Bradley Segal, Christopher D Shaffer, Kathryn E Sheldon, Erica M Shepard, Jonathan W Shepardson, Madav K Shroff, Jessica M Simmons, Erika F Simms, Brandy M Simpson, Kathryn M Sinclair, Robert L Sjoholm, Ingrid J Slette, Blaire C Spaulding, Clark L Straub, Joseph Stukey, Trevor Sughrue, Tin-Yun Tang, Lyons M Tatyana, Stephen B Taylor, Barbara J Taylor, Louise M Temple, Jasper V Thompson, Michael P Tokarz, Stephanie E Trapani, Alexander P Troum, Jonathan Tsay, Anthony T Tubbs, Jillian M Walton, Danielle H Wang, Hannah Wang, John R Warner, Emilie G Weisser, Samantha C Wendler, Kathleen A Weston-Hafer, Hilary M Whelan, Kurt E Williamson, Angelica N Willis, Hannah S Wirtshafter, Theresa W Wong, Phillip Wu, Yun jeong Yang, Brandon C Yee, David A Zaidins, Bo Zhang, Melina Y Zúniga, Roger W Hendrix, and Graham F Hatfull

Subjects
Medicine, Science
Abstract

Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists.

Published
2011
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