Article
Biochemical Research Methods
Yue Zhao, Lianbo Yu, Xue Wu, Haoran Li, Kevin R. Coombes, Kin Fai Au, Lijun Cheng, Lang Li
Summary: This study developed a statistical method called CEDA, which integrates gene expression data and CRISPR screening data for identifying essential genes. Compared to existing methods, CEDA shows higher sensitivity in detecting essential genes with moderate sgRNA fold change.
Article
Cell Biology
Xiaohua Duan, Xuming Tang, Manoj S. Nair, Tuo Zhang, Yunping Qiu, Wei Zhang, Pengfei Wang, Yaoxing Huang, Jenny Xiang, Hui Wang, Robert E. Schwartz, David D. Ho, Todd Evans, Shuibing Chen
Summary: Developing disease models to study SARS-CoV-2 infection is crucial, and research using airway organoids derived from human pluripotent stem cells has identified compounds that can block the virus. Further investigation reveals that these compounds inhibit SARS-CoV-2 infection by targeting the HIF1a-glycolysis axis.
Article
Biochemistry & Molecular Biology
Rui Tong Quek, Kierra S. Hardy, Stephen G. Walker, Dan T. Nguyen, Taciani de Almeida Magalhaes, Adrian Salic, Sujatha M. Gopalakrishnan, Pamela A. Silver, Timothy J. Mitchison
Summary: Biomolecular condensates formed by liquid-liquid phase separation have been implicated in multiple diseases. Modulation of condensate dynamics by small molecules has therapeutic potential, but so far, few condensate modulators have been disclosed. In this study, we show that N proteins from all seven human coronaviruses (HCoVs) vary in their tendency to undergo phase separation and identified small molecules that can regulate the assembly dynamics of N condensates. These findings have the potential to contribute to drug discovery for future pandemics.
ACS CHEMICAL BIOLOGY
(2023)
Article
Cell Biology
Nikki M. McCormack, Mahlet B. Abera, Eveline S. Arnold, Rebecca M. Gibbs, Scott E. Martin, Eugen Buehler, Yu-Chi Chen, Lu Chen, Kenneth H. Fischbeck, Barrington G. Burnett
Summary: The study uncovered pathways regulating SMN expression, providing new insights for treating SMA.
Article
Microbiology
Jamin Liu, Kristeene A. Knopp, Elze Rackaityte, Chung Yu Wang, Matthew T. Laurie, Sara Sunshine, Andreas S. Puschnik, Joseph L. DeRisi
Summary: This study identifies novel host factors associated with Lymphocytic choriomeningitis virus (LCMV) infection of human tissues, highlighting the importance of CD164 in viral entry and suggesting it as a potential therapeutic target for congenital infection.
Article
Biochemistry & Molecular Biology
Chushu Li, Han Yao, Huanbin Wang, Jing-Yuan Fang, Jie Xu
Summary: Amlodipine, identified as a potent inhibitor of PD-L1 expression, can increase CD8+ T-cell infiltration in tumor tissues and dose-dependently suppress tumor growth by blocking calcium flux. This reveals a calcium-dependent mechanism controlling PD-L1 degradation, emphasizing calcium flux blockade as a potential strategy for combinatorial immunotherapy.
Article
Cell Biology
Sahar Tavakoli, Vivian Garcia, Eric Gahwiler, Isaac Adatto, Apoorva Rangan, Kathleen A. Messemer, Sara Ashrafi Kakhki, Song Yang, Victoria S. Chan, Margot E. Manning, Haleh Fotowat, Yi Zhou, Amy J. Wagers, Leonard I. Zon
Summary: Stem cell transplantation is a potential cure for genetic disorders of skeletal muscle, but is currently limited by cell expansion and poor engraftment efficiency. In this study, a cross-species small-molecule screening platform using zebrafish and mice was developed to identify molecules that enhance myogenic activity and muscle engraftment. Two lipids, lysophosphatidic acid and niflumic acid, were found to promote muscle engraftment in both species by activating intracellular calcium-ion flux.
Article
Cell Biology
Johanna Michl, Yunyi Wang, Stefania Monterisi, Wiktoria Blaszczak, Ryan Beveridge, Esther M. Bridges, Jana Koth, Walter F. Bodmer, Pawel Swietach
Summary: Unlike most cell types, cancer cells can survive in low acid environments. Knocking out genes associated with pH-related fitness defects in colorectal cancer cells can cause cell death under acidic conditions. Researchers have also discovered mitochondrial metabolism inhibitors that can specifically kill cancer cells in a low acid environment. The growth of xenografts established from gene-knockout cells is slower, but can be stimulated with bicarbonate therapy to reduce tumor acid stress.
Article
Microbiology
David W. Morgens, Divya Nandakumar, Allison L. Didychuk, Kevin J. Yang, Britt A. Glaunsinger
Summary: This study demonstrates the use of CRISPR/Cas9 to rapidly create and screen thousands of mutant viruses in Kaposi's sarcoma-associated herpesvirus (KSHV). By analyzing the expression of viral genes in these mutant viruses, a novel required gene was identified and its specific function was characterized using targeted deep viral sequencing.
Article
Neurosciences
Arek Kendirli, Clara de la Rosa, Katrin F. Laemmle, Klara Eglseer, Isabel J. Bauer, Vladyslav Kavaka, Stephan Winklmeier, La Zhuo, Christian Wichmann, Lisa Ann Gerdes, Tania Kuempfel, Klaus Dornmair, Eduardo Beltran, Martin Kerschensteiner, Naoto Kawakami
Summary: This study identifies key regulators of T cell entry to the central nervous system (CNS) in a multiple sclerosis (MS) model using a CRISPR screen. The researchers found several essential brakes and facilitators of T cell migration, including the transcription factor ETS1 and functional modules centered around adhesion molecule α4-integrin, chemokine receptor CXCR3, and GRK2 kinase. Single-cell analysis of MS patients' T cells confirmed the correlation between the expression of these regulators and the ability of CD4+ T cells to reach the CNS.
NATURE NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Zied Boudhraa, Kossay Zaoui, Hubert Fleury, Maxime Cahuzac, Sophie Gilbert, Guergana Tchakarska, Jennifer Kendall-Dupont, Euridice Carmona, Diane Provencher, Anne-Marie Mes-Masson
Summary: The study demonstrates a new approach to target epithelial ovarian cancer survival by inhibiting Ran. There is an inverse correlation between Ran and NR1D1, playing a crucial role in aneuploid cells. Ran affects DNA repair pathways by destabilizing NR1D1 mRNA through miR4472 interference.
Article
Multidisciplinary Sciences
Amanda J. Collier, Adam Bendall, Charlene Fabian, Andrew A. Malcolm, Katarzyna Tilgner, Claudia Semprich, Katarzyna Wojdyla, Paola Serena Nisi, Kamal Kishore, Valar Nila Roamio Franklin, Bahar Mirshekar-Syahkal, Clive D'Santos, Kathrin Plath, Kosuke Yusa, Peter J. Rugg-Gunn
Summary: Identifying essential regulators and major impediments of human primed to naive pluripotent stem cell reprogramming through genome-wide screening, it was discovered that factors crucial for cell state change are typically repurposed with new functions rather than undergoing changes at the gene expression level. In addition, small-molecule inhibitors of reprogramming impediments were found to enhance naive cell reprogramming beyond current methods. This work not only defines principles controlling the establishment of human naive pluripotency, but also provides new insights into mechanisms destabilizing and reconfiguring cell identity during cell state transitions.
Article
Multidisciplinary Sciences
Chen Dong, Shuhua Fu, Rowan M. Karvas, Brian Chew, Laura A. Fischer, Xiaoyun Xing, Jessica K. Harrison, Pooja Popli, Ramakrishna Kommagani, Ting Wang, Bo Zhang, Thorold W. Theunissen
Summary: The authors systematically identify and characterize essential and growth-restricting genes in human trophoblast cells through a genome-wide CRISPR-Cas9 knockout screen. They reveal TEAD1 as a key regulator modulating chromatin architecture and gene expression to play a crucial role in the specification, maintenance, and differentiation of the human trophoblast lineage.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Diana G. Calvopina-Chavez, Robyn E. Howarth, Audrey K. Memmott, Oscar H. Pech H. Gonzalez, Caleb B. Hafen, Kyson T. Jensen, Alex B. Benedict, Jessica D. Altman, Brittany S. Burnside, Justin S. Childs, Samuel W. Dallon, Alexa C. DeMarco, Kirsten C. Flindt, Sarah A. Grover, Elizabeth Heninger, Christina S. Iverson, Abigail K. Johnson, Jack B. Lopez, McKay A. Meinzer, Brook A. Moulder, Rebecca I. Moulton, Hyrum S. Russell, Tiana M. Scott, Yuka Shiobara, Mason D. Taylor, Kathryn E. Tippets, Kayla M. Vainerere, Isabella C. Von Wallwitz, Madison Wagley, Megumi S. Wiley, Naomi J. Young, Joel S. Griffitts
Summary: This study investigates the genetic basis of flagellar motility and identifies 37 genes involved in flagellar biosynthesis, including previously unknown functions.
Article
Developmental Biology
Casey Ah-Cann, Verena C. Wimmer, Clare E. Weeden, Claire Marceaux, Charity W. Law, Laura Galvis, Caitlin E. Filby, Joy Liu, Kelsey Breslin, Tracy Willson, Matthew E. Ritchie, Marnie E. Blewitt, Marie-Liesse Asselin-Labat
Summary: The development of a branching tree in the embryonic lung is crucial for a fully mature functional lung at birth, with Sox9(+) cells playing a key role in this process. This study identified aurora kinase b (Aurkb) as an essential regulator of Sox9(+) cells, with its loss leading to insufficient branch development. The research demonstrates the potential of genetic screens in identifying regulators of lung development.
Article
Biochemistry & Molecular Biology
Randy J. Chandler, Ian M. Williams, Alana L. Gibson, Cristin D. Davidson, Arturo A. Incao, Brandon T. Hubbard, Forbes D. Porter, William J. Pavan, Charles P. Venditti
HUMAN MOLECULAR GENETICS
(2017)
Article
Genetics & Heredity
Craig A. Marshall, Dawn E. Watkins-Chow, Giampiero Palladino, Gail Deutsch, Keshav Chandran, William J. Pavan, Robert P. Erickson
Article
Oncology
Stacie K. Loftus
PIGMENT CELL & MELANOMA RESEARCH
(2018)
Article
Multidisciplinary Sciences
Julia C. Cronin, Stacie K. Loftus, Laura L. Baxter, Steve Swatkoski, Marjan Gucek, William J. Pavan
Review
Oncology
Laura L. Baxter, Dawn E. Watkins-Chow, William J. Pavan, Stacie K. Loftus
PIGMENT CELL & MELANOMA RESEARCH
(2019)
Article
Genetics & Heredity
Allison C. Fialkowski, Denise J. Levy, Dawn E. Watkins-Chow, Joseph W. Palmer, Roshan Darji, Hemant K. Tiwari, William J. Pavan, Melissa L. Harris
G3-GENES GENOMES GENETICS
(2019)
Article
Cell Biology
Jorge L. Rodriguez-Gil, Dawn E. Watkins-Chow, Laura L. Baxter, Gene Elliot, Ursula L. Harper, Stephen M. Wincovitch, Julia C. Wedel, Arturo A. Incao, Mylene Huebecker, Frederick J. Boehm, William S. Garver, Forbes D. Porter, Karl W. Broman, Frances M. Platt, William J. Pavan
DISEASE MODELS & MECHANISMS
(2020)
Article
Medicine, General & Internal
Jorge L. Rodriguez-Gil, Dawn E. Watkins-Chow, Laura L. Baxter, Tadafumi Yokoyama, Patricia M. Zerfas, Matthew F. Starost, William A. Gahl, May Christine V. Malicdan, Forbes D. Porter, Frances M. Platt, William J. Pavan
JOURNAL OF CLINICAL MEDICINE
(2020)
Article
Biochemistry & Molecular Biology
Jorge L. Rodriguez-Gil, Laura L. Baxter, Dawn E. Watkins-Chow, Nicholas L. Johnson, Cristin D. Davidson, Steven R. Carlson, Arturo A. Incao, Kerri L. Wallom, Nicole Y. Farhat, Frances M. Platt, Ryan K. Dale, Forbes D. Porter, William J. Pavan
Summary: The study analyzed RNA-Seq data from 42 NPC1 patient-derived fibroblast cell lines and identified 485 HP beta CD-responsive genes, showing significant involvement in cholesterol and lipid biosynthesis pathways. Experimental results in mice suggested that a gene, GPNMB, may serve as a useful biomarker of treatment response in NPC1 disease.
HUMAN MOLECULAR GENETICS
(2021)
Article
Genetics & Heredity
Stacie K. Loftus, Linnea Lundh, Dawn E. Watkins-Chow, Laura L. Baxter, Erola Pairo-Castineira, Ian J. Jackson, William S. Oetting, William J. Pavan, David R. Adams
Summary: Oculocutaneous albinism (OCA) is a heritable disorder of pigment production, and a complex structural variant (CxSV) in the OCA2 gene involving a 143 kb inverted segment has been identified as a potential genetic cause in some affected individuals. This discovery highlights the importance of comprehensive genetic testing for a complete molecular diagnosis in individuals with OCA who do not have identifiable mutations in known OCA genes.
Article
Multidisciplinary Sciences
Laura L. Baxter, Dawn E. Watkins-Chow, Nicholas L. Johnson, Nicole Y. Farhat, Frances M. Platt, Ryan K. Dale, Forbes D. Porter, William J. Pavan, Jorge L. Rodriguez-Gil
Summary: This study validates the use of LysoTracker as a predictor for age of onset and disease severity in NPC1 patients, using primary fibroblasts from a large cohort. The study also identifies a set of genes significantly associated with lysosomal defects or age of onset, particularly neurological symptom onset, and shows distinct expression patterns of these genes among patient subgroups.
SCIENTIFIC REPORTS
(2022)
Article
Genetics & Heredity
Stacie K. Loftus, Meredith F. Gillis, Linnea Lundh, Laura L. Baxter, Julia C. Wedel, Dawn E. Watkins-Chow, Frank X. Donovan, Yuri NISC Comparative Sequencing Program, Yuri Sergeev, William S. Oetting, William J. Pavan, David R. Adams
Summary: Oculocutaneous albinism (OCA) is a rare disorder characterized by decreased pigment production and visual-developmental changes. TYR mutations are common causes of OCA and a detailed analysis of TYR variants is necessary for identifying potentially disease-causing alleles. In this study, the analysis of high-depth short-read TYR sequencing data revealed various TYR variants, including a common disease-causing haplotype (p.[Ser192Tyr; Arg402Gln]) present in a significant number of OCA probands. Identification of phased variants is crucial for a comprehensive assessment of potentially disease-causing alleles.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Oncology
H. Matthew Berns, Dawn E. Watkins-Chow, Sizhu Lu, Pakavarin Louphrasitthiphol, Tongwu Zhang, Kevin M. Brown, Pedro Moura-Alves, Colin R. Goding, William J. Pavan
Summary: This study used single-cell RNA sequencing to define a MC1R-inhibited Gene Signature in red-haired mouse models, which includes previously unidentified genes related to melanogenesis and oncogenic transformation. The results identified TBX3 as a potential gene involved in regulating melanogenesis and senescence bypass.
PIGMENT CELL & MELANOMA RESEARCH
(2023)