Article
Biochemistry & Molecular Biology
Qingdan Du, Yen-Hua Huang, Conan K. Wang, Quentin Kaas, David J. Craik
Summary: Cyclotides are a family of macrocyclic peptides with diverse bioactivities. Understanding the role of individual residues in their structure and function has been challenging, particularly for the bracelet subfamily. This study investigated the role of specific residues in bracelet cyclotides through mutagenesis, revealing their importance in maintaining structure, membrane binding, and cytotoxic activity. These findings provide valuable insights for future biotechnological applications of bracelet cyclotides.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Cell Biology
Mohammad Houshmand, Nicoletta Vitale, Francesca Orso, Alessandro Cignetti, Ivan Molineris, Valentina Gaidano, Stefano Sainas, Marta Giorgis, Donatella Boschi, Carmen Fava, Alice Passoni, Marta Gai, Massimo Geuna, Federica Sora, Alessandra Iurlo, Elisabetta Abruzzese, Massimo Breccia, Olga Mulas, Giovanni Caocci, Fausto Castagnetti, Daniela Taverna, Salvatore Oliviero, Fabrizio Pane, Marco Lucio Lolli, Paola Circosta, Giuseppe Saglio
Summary: The study shows that the newly developed DHODH inhibitor, Meds433, is highly effective in targeting CML cells by activating the apoptotic pathway and inducing metabolic stress. This finding suggests that DHODH inhibition is a promising approach for targeting CML stem/progenitor cells.
CELL DEATH & DISEASE
(2022)
Article
Hematology
Sangeetha Venugopal, John Mascarenhas
Summary: Myelofibrosis (MF) can lead to splenomegaly and thrombocytopenia. Currently approved JAK1/2 inhibitors have not been evaluated in patients with platelets <= 50 x 109/L. Pacritinib (PAC), a selective JAK2 inhibitor, has shown efficacy in MF patients, especially in splenic response and symptom improvement.
Article
Biotechnology & Applied Microbiology
Ziyi Yang, Ryan S. Wang, Billy Y. Cheng, Vincent Ruan, Piju Yang, Chen-Hsien Liang, Claire R. Shen
Summary: This study identified two critical residues, M185 and V402, of the flavin-containing monooxygenase from Corynebacterium glutamicum (CgFMO) and generated variants with enhanced indole hydroxylation activity. The best performing mutant M185L/V402A exhibited nearly 10 fold higher catalytic efficiency and greater improvement in the kcat level compared to wild type CgFMO. The study provides insight into the CgFMO active site and aids in the future design of FMO biocatalysts.
BIOCHEMICAL ENGINEERING JOURNAL
(2023)
Article
Chemistry, Medicinal
Parthiban Marimuthu, Suresh Gorle, Konda Reddy Karnati
Summary: This study employed multiple computational approaches to investigate the mechanistic basis of high-affinity inhibitors for the main protease of SARS-CoV-2, providing insights into potential anti-M-pro strategies.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Oncology
Charly Courdy, Loic Platteeuw, Charlotte Ducau, Isabelle De Araujo, Emeline Boet, Ambrine Sahal, Estelle Saland, Valerie Edmond, Suzanne Tavitian, Sarah Bertoli, Pierre Cougoul, Fanny Granat, Laura Poillet, Caroline Marty, Isabelle Plo, Jean-Emmanuel Sarry, Stephane Manenti, Veronique Mansat-De Mas, Carine Joffre
Summary: This study demonstrates that ruxolitinib induces autophagy through the activation of PP2A in JAK2(V617F) cells, and inhibiting autophagy or PP2A activity enhances the inhibitory effect of ruxolitinib on MPN cells. Additionally, a novel autophagy inhibitor, Lys05, improves the sensitivity to ruxolitinib and enhances the treatment efficacy for MPN patients.
BLOOD CANCER JOURNAL
(2023)
Article
Oncology
Paul Yenerall, Rahul K. Kollipara, Kimberley Avila, Michael Peyton, Christopher A. Eide, Daniel Bottomly, Shannon K. McWeeney, Yan Liu, Kenneth D. Westover, Brian J. Druker, John D. Minna, Ralf Kittler
Summary: LentiMutate technology efficiently identifies drug resistance mutations in drug targets by leveraging the error-prone nature of HIV-1 reverse transcriptase. This technique, validated with clinically relevant EGFR resistance mutations, has been successfully applied to multiple clinical anticancer drugs, uncovering novel resistance mutations in imatinib and AMG 510.
Article
Oncology
Yuanquan Yang, Sarah P. Psutka, Anish B. Parikh, Mingjia Li, Katharine Collier, Abdul Miah, Sherry Mori, Megan Hinkley, Scott S. Tykodi, Evan Hall, John A. Thompson, Ming Yin
Summary: The combination of immune checkpoint inhibitor/tyrosine kinase inhibitor (ICI/TKI) is a new standard of care for the initial treatment of metastatic renal cell carcinoma (mRCC), but its efficacy and toxicity beyond the first-line setting are still uncertain.
Article
Immunology
Yueqing Han, Haoxin Song, Yanshan Li, Rongxin Li, Ling Chen, Bo Gao, Yijun Chen, Shuzhen Wang
Summary: The combination of tetracycline antibiotics, demeclocycline (D), chlortetracycline (C), and minocycline (M), showed therapeutic potential against liver fibrosis by inhibiting the activation of hepatic stellate cells and the MAPK signaling. This study suggests that tetracyclines may be repurposed for the treatment of liver fibrosis.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2024)
Article
Immunology
Eszter Kaposztas, Lili Balogh, Attila Mocsai, Eva Kemecsei, Zoltan Jakus, Tamas Nemeth
Summary: Autoimmune arthritis, such as rheumatoid arthritis, affects a significant portion of the population and current therapies often fail to provide complete relief. Research suggests that inhibiting Syk tyrosine kinase can effectively reduce joint inflammation, mainly by targeting neutrophil functions.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Lukas M. Braun, Robert Zeiser
Summary: Allogeneic hematopoietic stem cell transplantation is an effective therapy for hematological malignancies, but is limited by severe graft-versus-host disease. Research shows that targeting kinase activity with small molecule inhibitors has potential in reducing GvHD severity while preserving GvL activity.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Mitchell D. Meyer, Jasmine Winzeler, Sophia M. Taylor, Alex Kilgore, Kimberly Edicha, Chase Chitwood, Zachary Spearin, S. K. Nadia Rahman Silvia, Ronith Chakraborty, Jesse E. Smith, Bridget Kennedy, Carson Zois, Hayley Cawthon, Mukiri Gilruth, Steven K. Backues
Summary: Selective autophagy is a cellular process that degrades damaged or toxic cytoplasmic components, and Atg11 is a key adapter protein involved in this process. We identified three critical residues in the coiled-coil 2 domain of Atg11 that are required for its structure and function.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Carlos Santolaria, Diego Velazquez, Marcel Albacar, Antonio Casamayor, Joaquin Arino
Summary: The function of the Ppz1 phosphatase in Saccharomyces cerevisiae is controlled by its inhibitory subunit Hal3. Hal3 is a moonlighting protein involved in the CoA biosynthetic pathway. Deletion or specific mutations in a region of Hal3's N-terminal extension compromise its function as a Ppz1 inhibitor without affecting its ability to interact with the phosphatase. The presence of a specific sequence explains the unexpected ability of Cab3 to regulate Ppz1 function in Candida albicans. This study contributes to our understanding of Ppz phosphatase regulation and its importance in pathogenic fungi.
Review
Biochemistry & Molecular Biology
Bernhard Moser, Sophie Edtmayer, Agnieszka Witalisz-Siepracka, Dagmar Stoiber
Summary: Aberrant JAK-STAT signaling in acute myeloid leukemia (AML) plays a crucial role in disease pathogenesis. Targeting the JAK-STAT pathway, particularly constitutively activated STAT3 and STAT5, has shown promising results in vitro and in vivo. Ongoing development of new JAK-STAT inhibitors with better disease specificity offers potential for improved disease management.
Article
Oncology
Tamara K. Moyo, Ashwin Kishtagari, Matthew T. Villaume, Brandon McMahon, Sanjay R. Mohan, Tess Stopczynski, Sheau-Chiann Chen, Run Fan, Yuankai Huo, Hyeonsoo Moon, Yucheng Tang, Cosmin A. Bejan, Merrida Childress, Ingrid Anderson, Kyle Rawling, Rhea M. Simons, Ashley Moncrief, Rebekah Caza, Laura Dugger, Aunshka Collins, Channing Dudley, P. Brent Ferrell, Michael Byrne, Stephen A. Strickland, Gregory D. Ayers, Bennett A. Landman, Emily F. Mason, Ruben A. Mesa, Jeanne M. Palmer, Laura C. Michaelis, Michael R. Savona
Summary: This study evaluated the safety and efficacy of a combination treatment of a selective PI3KS inhibitor, umbralisib, and a JAK inhibitor, ruxolitinib, for patients with MF. The results showed that the combination treatment was well tolerated and could potentially resensitize patients to ruxolitinib.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Lianne E. Rotin, Marcela Gronda, Neil MacLean, Rose Hurren, XiaoMing Wang, Feng-Hsu Lin, Jeff Wrana, Alessandro Datti, Dwayne L. Barber, Mark D. Minden, Malik Slassi, Aaron D. Schimmer
Article
Medicine, Research & Experimental
Ju Huang, Yuanfeng Liu, Bryan C. Au, Dwayne L. Barber, Andrea Arruda, Axel Schambach, Michael Rothe, Mark D. Minden, Christopher J. Paige, Jeffrey A. Medin
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2016)
Article
Medicine, Research & Experimental
Ju Huang, Aneal Khan, Bryan C. Au, Dwayne L. Barber, Lucia Lopez-Vasquez, Nicole L. Prokopishyn, Michel Boutin, Michael Rothe, Jack W. Rip, Mona Abaoui, Murtaza S. Nagree, Shaalee Dworski, Axel Schambach, Armand Keating, Michael L. West, John Klassen, Patricia V. Turner, Sandra Sirrs, C. Anthony Rupar, Christiane Auray-Blais, Ronan Foley, Jeffrey A. Medin
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2017)
Editorial Material
Hematology
Dwayne L. Barber
Article
Biochemistry & Molecular Biology
Mojib Javadi, Edda Hofstaetter, Natalie Stickle, Bryan K. Beattie, Robert Jaster, Christin Carter-Su, Dwayne L. Barber
JOURNAL OF BIOLOGICAL CHEMISTRY
(2012)
Article
Biochemistry & Molecular Biology
Mojib Javadi, Terri D. Richmond, Kai Huang, Dwayne L. Barber
JOURNAL OF BIOLOGICAL CHEMISTRY
(2013)
Article
Oncology
K. M. Badger-Brown, L. C. Gillis, M. L. Bailey, J. M. Penninger, D. L. Barber
Article
Oncology
L. C. Gillis, D. M. Berry, M. D. Minden, C. J. McGlade, D. L. Barber
Article
Multidisciplinary Sciences
Masato Sasaki, Christiane B. Knobbe, Joshua C. Munger, Evan F. Lind, Dirk Brenner, Anne Bruestle, Isaac S. Harris, Roxanne Holmes, Andrew Wakeham, Jillian Haight, Annick You-Ten, Wanda Y. Li, Stefanie Schalm, Shinsan M. Su, Carl Virtanen, Guido Reifenberger, Pamela S. Ohashi, Dwayne L. Barber, Maria E. Figueroa, Ari Melnick, Juan-Carlos Zuniga-Pfluecker, Tak W. Mak
Article
Multidisciplinary Sciences
Nicole M. Anderson, Mojib Javadi, Elizabeth Berndl, Zorana Berberovic, Monica L. Bailey, Kai Huang, Ann M. Flenniken, Lucy R. Osborne, S. Lee Adamson, Janet Rossant, Christin Carter-Su, Chen Wang, Kelly M. McNagny, Robert F. Paulson, Mark D. Minden, William L. Stanford, Dwayne L. Barber
Article
Multidisciplinary Sciences
Aneal Khan, Dwayne L. Barber, Ju Huang, C. Anthony Rupar, Jack W. Rip, Christiane Auray-Blais, Michel Boutin, Pamela O'Hoski, Kristy Gargulak, William M. McKillop, Graeme Fraser, Syed Wasim, Kaye LeMoine, Shelly Jelinski, Ahsan Chaudhry, Nicole Prokopishyn, Chantal F. Morel, Stephen Couban, Peter R. Duggan, Daniel H. Fowler, Armand Keating, Michael L. West, Ronan Foley, Jeffrey A. Medin
Summary: Enzyme and chaperone therapies for Fabry disease are expensive, intrusive, and not fully efficacious. A pilot study was conducted using gene therapy with autologous, lentivirus-transduced hematopoietic cells expressing alpha-galactosidase A, showing safety and promising results in five patients.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Ben J. Eves, Teklab Gebregiworgis, Douglas A. Kuntz, Gilbert G. Prive, Christopher B. Marshall, Mitsuhiko Ikura, Genevieve M. C. Gasmi-Seabrook
Summary: This study reveals the interaction mechanism and conformational changes between KRAS and RGL1-RA through crystal structures and solution experiments. The distance and angle between the RAS alpha1 helix and the RBD/RA alpha1 helix were found to differ significantly among KRAS and RBD/RA complexes, with the largest distance observed in the KRAS/RGL1-RA structures. Furthermore, unique structural signatures involving contacts between the beta1-beta2 loop of RA and the alpha1 helix of RAS were identified, clearly distinguishing the KRAS/RGL1-RA complexes from RAS/RBD complexes.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Husna Anwar, Andrew Johnston, Suhas Mahesh, Kamalpreet Singh, Zhibo Wang, Douglas A. Kuntz, Isaac Tamblyn, Oleksandr Voznyy, Gilbert G. Prive, Edward H. Sargent
Summary: High-throughput experimentation (HTE) is employed to accelerate the exploration of materials space, specifically in the field of metal halide perovskites (MHPs). A workflow is developed to synthesize and characterize light-emitting MHP single crystals, generating an experimentally derived photoluminescence spectra data set for low-dimensional MHPs. The accelerated workflow is used to optimize the synthesis and emission of a new MHP, and a large number of MHP single crystals are synthesized and measured to study the effects of synthesis parameters and compositional engineering on the emission intensity. Insights from this analysis are used to screen an existing database for potentially emissive MHPs, and top candidates for future exploration are presented. As a proof of concept, one of these candidates is used to synthesize an MHP with a photoluminescence quantum yield of 10%.
ACS CENTRAL SCIENCE
(2022)
Meeting Abstract
Chemistry, Multidisciplinary
Gilbert Prive, Douglas Kuntz, Gennady Poda, Methvin Isaac, Rima Al-awar
ACTA CRYSTALLOGRAPHICA A-FOUNDATION AND ADVANCES
(2018)