Review
Virology
Ugo Moens, Sara Passerini, Mar Falquet, Baldur Sveinbjornsson, Valeria Pietropaolo
Summary: Protein phosphorylation and dephosphorylation are common post-translational modifications that can modulate protein function. Phosphorylation of viral proteins plays an important role in the virus life cycle.
Article
Virology
Wei Zou, Michael J. Imperiale
Summary: BK polyomavirus is a virus that establishes a lifelong infection in most people. In transplant recipients with suppressed immune systems, uncontrolled virus replication can cause severe disease. The small T antigen of BK polyomavirus plays important roles in regulating viral replication, the innate immune response, apoptosis, and transformation.
JOURNAL OF VIROLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Mingyi Li, Chenxia Li, Huarong Zheng, Zhen Zhou, Wenjian Yang, Yu Gong, Xia Wu, Leyu Li
Summary: The study uncovers the role of circ_0001795/miR-339-5p/YAP1 axis in regulating osteogenic differentiation in osteoporosis, suggesting circ_0001795 as a potential therapeutic target.
Article
Oncology
Kelly L. Harms, Lili Zhao, Bryan Johnson, Xiaoming Wang, Shannon Carskadon, Nallasivam Palanisamy, Daniel R. Rhodes, Rahul Mannan, Josh N. Vo, Jae Eun Choi, May P. Chan, Douglas R. Fullen, Rajiv M. Patel, Javed Siddiqui, Vincent T. Ma, Steven Hrycaj, Scott A. McLean, Tasha M. Hughes, Christopher K. Bichakjian, Scott A. Tomlins, Paul W. Harms
Summary: The study classified Merkel cell carcinoma (MCC) tumors into virus-positive (VP) and virus-negative (VN) types, each displaying distinct sets of prognostic molecular biomarkers. MCPyV status was found to be an independent prognostic factor for MCC, with tumor genome, transcriptome, and microenvironment features modifying prognosis in a manner specific to viral status.
CLINICAL CANCER RESEARCH
(2021)
Article
Medicine, Research & Experimental
Thomas C. Frost, Ashley K. Gartin, Mofei Liu, Jingwei Cheng, Harita Dharaneeswaran, Derin B. Keskin, Catherine J. Wu, Anita Giobbie-Hurder, Manisha Thakuria, James A. DeCaprio
Summary: This study reveals a previously unrecognized heterogeneity in the gene expression of Merkel cell carcinoma (MCC) and identifies an inverse correlation between neuroendocrine gene expression and the Hippo pathway transcription factors YAP1 and WWTR1. The expression of YAP1 or WWTR1 induces cell-cycle arrest in MCPyV-positive MCC cell lines through the TEAD-dependent repression of MCPyV LT. These findings shed light on the development of MCPyV-positive MCC and have implications for diagnosis and potential therapeutic interventions.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Multidisciplinary Sciences
Jong Hoon Won, Jacob S. Choi, Joon-Il Jun
Summary: This study reveals that the matricellular protein CCN1 is a niche factor for intestinal stem cells, regulating their proliferation and differentiation through integrin signaling. CCN1 interacts with integrins alpha(v)beta(3)/alpha(v)beta(5) to activate distinct downstream pathways, leading to Notch activation for differentiation via NF-kappaB and Wnt signaling control for proliferation via Src-mediated YAP activation and Dkk1 expression. Moreover, CCN1 and YAP amplify each other's activities in a regulatory loop.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Meng Chen, Yuan Dong, Lijie Tian, Jie Zhou, Endong Zhu, Hairui Yuan, Xiaoxia Li, Baoli Wang
Summary: MTSS1 promotes adipocyte differentiation by interacting with PTPRD to activate SFKs, such as FYN tyrosine kinase.
Article
Cell Biology
Nicholas Marano, James M. Holaska
Summary: This study found that the functional interaction between emerin and HDAC3, EZH2, and G9a is crucial for myogenic differentiation. By using emerin mutant cell lines and small molecule inhibitors, the researchers discovered that these interactions play a regulatory role in the process of muscle differentiation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Zheng Fu, Joseph W. Dean, Lifeng Xiong, Michael W. Dougherty, Kristen N. Oliff, Zong-ming E. Chen, Christian Jobin, Timothy J. Garrett, Liang Zhou
Summary: The authors found that mitochondrial transcription factor A plays a crucial role in regulating intestinal RORγt(+) lymphocyte homeostasis and metabolic control in mice. Deletion of Tfam affects the maintenance of γδT17 cells and the number of ILC3s, leading to intestinal tissue remodeling and growth.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Rui Sun, Siying Guo, Yoko Shuda, Anish B. Chakka, Lora H. Rigatti, Guangyi Zhao, Mohammed A. E. Ali, Christopher Y. Park, Uma Chandran, Jian Yu, Christopher J. Bakkenist, Masahiro Shuda, Patrick S. Moore, Yuan Chang
Summary: 4E-BP1 is a tumor suppressor that regulates cap-dependent translation through phosphorylation by mechanistic target of rapamycin (mTOR) or cyclin-dependent kinase 1 (CDK1). The phosphorylation of 4E-BP1 serine 82 (S82) by CDK1, but not mTOR, during mitosis has unknown consequences. Knock-in mice with a single S82A substitution in 4E-BP1 were generated and showed no developmental or behavioral abnormalities, but developed polycystic liver and kidney disease and lymphoid malignancies upon aging and irradiation. Further analysis identified PTEN mutations and impaired expression in lymphomas derived from S82A mice. This study suggests that the absence of 4E-BP1(S82) phosphorylation may predispose to polycystic proliferative disease and lymphoma under certain stressful conditions.
Article
Biochemistry & Molecular Biology
Svenja Michalek, Thomas Goj, Anna Pia Plazzo, Blerim Marovca, Beat Bornhauser, Thomas Brunner
Summary: Nuclear receptors are transcription factors that play important roles in physiological and pathological processes. Glucocorticoids are essential for treating T-cell acute lymphoblastic leukemia (T-ALL), but resistance to glucocorticoid treatment is associated with poor prognosis and high risk of relapse. The study reveals that the interaction between glucocorticoid receptor (GR) and Liver Receptor Homolog-1 (LRH-1) critically regulates glucocorticoid sensitivity in T-ALL, providing new perspectives for developing therapeutic approaches to overcome glucocorticoid resistance.
Article
Microbiology
Cindy Chiang, Steve Dvorkin, Jessica J. Chiang, Rachel B. Potter, Michaela U. Gack
Summary: JCV infection in human astrocytes is controlled by innate immune sensors RIG-I and cGAS, with the small t antigen of JCV acting as an interferon antagonist. This highlights how JCV and related viruses manipulate innate immune pathways, potentially sparking research into novel therapies.
Article
Biochemistry & Molecular Biology
Jeremy R. B. Newman, Patrick Concannon, Yan Ge
Summary: UBASH3A is a negative regulator of T cell activation and IL-2 production and its relationship with other T1D risk factors is largely unknown. This study reveals a physical interaction between UBASH3A and PTPN22 in T cells, independent of a T1D risk coding variant in PTPN22. Additionally, UBASH3A and PTPN22 transcripts cooperatively affect IL2 expression in human primary CD8(+) T cells, and two independent T1D risk variants in UBASH3A and PTPN22 have a statistical interaction, jointly influencing T1D risk.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Lakshminarayan Reddy Teegala, Ravindra Gudneppanavar, Emma Elizabeth Sabu Kattuman, Matthew Snyderman, Arani Varamuniprasad Thanusha, Venkatesh Katari, Charles K. Thodeti, Sailaja Paruchuri
Summary: Prostaglandin E-2 (PGE(2)) inhibits fibroblast differentiation mediated by TGF beta 1 by interacting with EP2R and EP4R, and its inhibitory effect is mediated through the phosphorylation/inactivation of YAP. This study reveals the importance of PGE(2)-YAP interactions in fibroblast differentiation and provides a novel therapeutic target for conditions associated with myofibroblasts like asthma.
Article
Biochemistry & Molecular Biology
Meng Zhao, Ariel Quintana, Chen Zhang, Alexander Y. Andreyev, William Kiosses, Tomomi Kuwana, Anne Murphy, Patrick G. Hogan, Mitchell Kronenberg
Summary: The differentiation of NKT2 cells requires higher and sustained calcium signals compared to their NKT1 counterparts, which is connected with mitochondria and cellular metabolism.
Article
Multidisciplinary Sciences
Sylvan C. Baca, David Y. Takeda, Ji-Heui Seo, Justin Hwang, Sheng Yu Ku, Rand Arafeh, Taylor Arnoff, Supreet Agarwal, Connor Bell, Edward O'Connor, Xintao Qiu, Sarah Abou Alaiwi, Rosario I. Corona, Marcos A. S. Fonseca, Claudia Giambartolomei, Paloma Cejas, Klothilda Lim, Monica He, Anjali Sheahan, Amin Nassar, Jacob E. Berchuck, Lisha Brown, Holly M. Nguyen, Ilsa M. Coleman, Arja Kaipainen, Navonil De Sarkar, Peter S. Nelson, Colm Morrissey, Keegan Korthauer, Mark M. Pomerantz, Leigh Ellis, Bogdan Pasaniuc, Kate Lawrenson, Kathleen Kelly, Amina Zoubeidi, William C. Hahn, Himisha Beltran, Henry W. Long, Myles Brown, Eva Corey, Matthew L. Freedman
Summary: The study reveals that the transcription factor FOXA1 plays a crucial role in the development of neuroendocrine prostate cancer (NEPC) by regulating specific regulatory elements. Additionally, the expression of NE lineage TFs ASCL1 and NKX2-1 in PRAD cells can reprogram FOXA1 to bind to NE regulatory elements and induce enhancer activity.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Anna E. Prizment, Sean McSweeney, Nathan Pankratz, Corinne E. Joshu, Justin H. Hwang, Elizabeth A. Platz, Charles J. Ryan
Summary: The alterations in androgen-regulating genes can impact the prognosis of prostate cancer, with HSD3B1 gene variation associated with increased risk of prostate cancer death in men with metastatic disease. There is a cumulative effect of these genes on prostate cancer-specific mortality, with further validation needed.
Article
Cell Biology
Chao Dai, Jonathan P. Rennhack, Taylor E. Arnoff, Maneesha Thaker, Scott T. Younger, John G. Doench, August Yue Huang, Annan Yang, Andrew J. Aguirre, Belinda Wang, Evan Mun, Joyce T. O'Connell, Ying Huang, Katherine Labella, Jessica A. Talamas, Ji Li, Nina Ilic, Justin Hwang, Andrew L. Hong, Andrew O. Giacomelli, Ole Gjoerup, David E. Root, William C. Hahn
Summary: Metastasis is a complex and poorly understood process, especially in pancreatic cancer where loss of SMAD4 is correlated with metastatic disease and poor prognosis. This study identified FOSL1 as a SMAD4 target that plays a critical role in driving colonization to the lung, suggesting that early targeting of these genes may provide therapeutic benefits.
Article
Cell Biology
Miju Kim, Seav Huong Ly, Yingtian Xie, Gina N. Duronio, Dane Ford-Roshon, Justin H. Hwang, Rita Sulahian, Jonathan P. Rennhack, Jonathan So, Ole Gjoerup, Jessica A. Talamas, Maximilien Grandclaudon, Henry W. Long, John G. Doench, Nilay S. Sethi, Marios Giannakis, William C. Hahn
Summary: Transcriptional co-activator YAP1 is crucial for cell proliferation, survival, and tumorigenesis. This study reveals that the transcription factor PRDM14 can rescue YAP1-dependent colon cancer cells by upregulating the expression of CALM2 and SLC2A1.
DEVELOPMENTAL CELL
(2022)
Article
Multidisciplinary Sciences
Haitham A. Elmarakeby, Justin Hwang, Rand Arafeh, Jett Crowdis, Sydney Gang, David Liu, Saud H. AlDubayan, Keyan Salari, Steven Kregel, Camden Richter, Taylor E. Arnoff, Jihye Park, William C. Hahn, Eliezer M. Van Allen
Summary: The development of a biologically informed deep learning model P-NET enables stratification of prostate cancer patients by treatment-resistance state and evaluation of molecular drivers of treatment resistance for therapeutic targeting with complete model interpretability. This approach shows superior performance in cancer state prediction using molecular data compared to other modeling approaches.
Article
Cell Biology
Stephen Tang, Vidyalakshmi Sethunath, Nebiyou Y. Metaferia, Marina F. Nogueira, Daniel S. Gallant, Emma R. Garner, Lauren A. Lairson, Christopher M. Penney, Jiao Li, Maya K. Gelbard, Sarah Abou Alaiwi, Ji-Heui Seo, Justin H. Hwang, Craig A. Strathdee, Sylvan C. Baca, Shatha AbuHammad, Xiaoyang Zhang, John G. Doench, William C. Hahn, David Y. Takeda, Matthew L. Freedman, Peter S. Choi, Srinivas R. Viswanathan
Summary: AR signaling in prostate cancer is driven by protein arginine methyltransferase 1 (PRMT1), which regulates AR recruitment and expression. Inhibition of PRMT1 impairs AR binding at specific sites and decreases expression of key oncogenes. Combined inhibition of AR and PRMT1 shows unique sensitivity in AR-driven prostate cancer cells.
Article
Biology
Justin H. Hwang, Rand Arafeh, Ji-Heui Seo, Sylvan C. Baca, Megan Ludwig, Taylor E. Arnoff, Lydia Sawyer, Camden Richter, Sydney Tape, Hannah E. Bergom, Sean McSweeney, Jonathan P. Rennhack, Sarah A. Klingenberg, Alexander T. M. Cheung, Jason Kwon, Jonathan So, Steven Kregel, Eliezer M. Van Allen, Justin M. Drake, Matthew L. Freedman, William C. Hahn
Summary: The study reveals the physical interactions between CREB5, AR, and FOXA1 in mCRPC, and their association with critical nuclear factors and pathways that promote ART resistance.
Article
Oncology
Xiaolei Shi, Abderrahman Day, Hannah E. Bergom, Sydney Tape, Sylvan C. Baca, Zoi E. Sychev, Gabrianne Larson, Asha Bozicevich, Justin M. Drake, Nicholas Zorko, Jinhua Wang, Charles J. Ryan, Emmanuel S. Antonarakis, Justin Hwang
Summary: The study identifies B7-H3 as an immune checkpoint overexpressed in prostate cancer, particularly in metastatic castration-resistant prostate cancer (mCRPC). Enzalutamide-resistant mCRPC cells show increased expression of B7-H3, and it is associated with resistance signaling pathways. The gene network of B7-H3 is strongly correlated with androgen receptor (AR) and its co-factors, suggesting potential therapeutic targets for mCRPC.
NPJ PRECISION ONCOLOGY
(2022)
Article
Endocrinology & Metabolism
Song Yi Bae, Hannah E. Bergom, Abderrahman Day, Joseph T. Greene, Zoi E. Sychev, Gabrianne Larson, Eva Corey, Stephen R. Plymate, Tanya S. Freedman, Justin H. Hwang, Justin M. Drake
Summary: Neuroendocrine prostate cancer (NEPC) is an aggressive subtype characterized by loss of androgen receptor signaling and transdifferentiation toward small-cell neuroendocrine phenotypes. Using SCN phenotype scores and gene depletion screens, ZBTB7A was identified as a candidate promoting NEPC progression. High SCN phenotype scores correlated with reliance on RET kinase activity and dependence on ZBTB7A. ZBTB7A showed distinct gene networking patterns in NEPC compared to prostate adenocarcinoma, with a strong association with genes promoting cell cycle progression. Silencing ZBTB7A suppressed cell growth and induced apoptosis in NEPC cell lines.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biology
Hannah E. Bergom, Ashraf Shabaneh, Abderrahman Day, Atef Ali, Ella Boytim, Sydney Tape, John R. Lozada, Xiaolei Shi, Carlos Perez Kerkvliet, Sean McSweeney, Samuel P. Pitzen, Megan Ludwig, Emmanuel S. Antonarakis, Justin M. Drake, Scott M. Dehm, Charles J. Ryan, Jinhua Wang, Justin Hwang
Summary: ALAN is an informatics approach that develops gene signatures, identifies gene targets, and interprets mechanisms of cancer progression or therapy resistance. It compares gene behavior based on patient -omic data, identifying various types of gene behaviors. ALAN discovered direct protein-protein interactions in prostate cancer and complex networks associated with the proto-oncogene MYC in different cancer types and within cancer subtypes.
COMMUNICATIONS BIOLOGY
(2023)
Article
Oncology
Alex Chehrazi-Raffle, Hanna Tukachinsky, Eamon Toye, Smruthy Sivakumar, Alexa B. Schrock, Hannah E. Bergom, Hedyeh Ebrahimi, Sumanta Pal, Tanya Dorff, Neeraj Agarwal, Brandon A. Mahal, Geoffrey R. Oxnard, Justin Hwang, Emmanuel S. Antonarakis
Summary: In this study, the nature of BRAF alterations in prostate cancer was characterized using comprehensive genomic profiling of tissue and liquid biopsies. The results showed that activating BRAF alterations were detected in approximately 3% of prostate cancers, with the majority being class II mutations and rearrangements. These BRAF-altered prostate cancers were enriched for CDK12 mutations but depleted in TMPRSS2 fusions, PTEN alterations, and APC alterations. Furthermore, BRAF alterations were more common in tumors from patients of African and Asian ancestry compared to patients of European ancestry.
CLINICAL CANCER RESEARCH
(2023)
Article
Cell Biology
Frank Cichocki, Bin Bin Zhang, Cheng-Ying Wu, Emily Chiu, Abderrahman Day, Roddy S. O'Connor, Dima Yackoubov, Ronit Simantov, David H. McKenna, Qing Cao, Todd E. Defor, Murali Janakiram, Rose Wangen, Zuzan Cayci, Nathaniel Snyder, Akhilesh Kumar, Bartosz Grzywacz, Justin Hwang, Yona Geffen, Jeffrey S. Miller, Joseph Maakaron, Veronika Bachanova
Summary: Allogeneic natural killer (NK) cell adoptive transfer, enhanced by ex vivo culture with interleukin-15 (IL-15) and nicotinamide (NAM), leads to stable induction of l-selectin (CD62L), and metabolic changes associated with elevated glucose flux. This approach improves NK cell survival, function, and persistence, and shows promising results in a clinical trial for patients with relapsed or refractory non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). The therapy, named GDA-201, demonstrates high tolerability, favorable metabolic profile, and an overall response rate of 74% in advanced NHL patients.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Editorial Material
Endocrinology & Metabolism
John T. Phoenix, Audris Budreika, Raymond J. Kostlan, Justin H. Hwang, Sean W. Fanning, Steven Kregel
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Oncology
Ralph E. E. White, Maxwell Bannister, Abderrahman Day, Hannah E. E. Bergom, Victor M. M. Tan, Justin Hwang, Hai Dang Nguyen, Justin M. M. Drake
Summary: Prostate cancer (PCa) is the most diagnosed non-skin cancer in American males. Patients with localized prostate cancer are treated with androgen deprivation therapies (ADTs), which inhibit androgen production and the androgen receptor (AR). However, some patients develop resistance to ADTs and progress to castration-resistant prostate cancer (CRPC). In this study, the researchers found that the SRC kinase inhibitor, saracatinib, synergizes with enzalutamide, a second-generation hormonal therapy, in specific types of CRPC cell lines. This combination strategy could potentially improve treatment outcomes for patients expressing both AR-FL and AR-Vs.
FRONTIERS IN ONCOLOGY
(2023)
Article
Medicine, Research & Experimental
Raie T. Bekele, Amruta S. Samant, Amin H. Nassar, Jonathan So, Elizabeth P. Garcia, Catherine R. Curran, Justin H. Hwang, David L. Mayhew, Anwesha Nag, Aaron R. Thorner, Judit Borcsok, Zsofia Sztupinszki, Chong-Xian Pan, Joaquim Bellmunt, David J. Kwiatkowski, Guru P. Sonpavde, Eliezer M. Van Allen, Kent W. Mouw
Summary: The study identified RAF1 activation as a dependency in a subset comprising nearly 20% of urothelial tumors, suggesting that targeting RAF1-mediated signaling may represent a rational therapeutic strategy.
JOURNAL OF CLINICAL INVESTIGATION
(2021)