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Article ; Online: The role of transcription factors in shaping regulatory T cell identity.

Trujillo-Ochoa, Jorge L / Kazemian, Majid / Afzali, Behdad

2023 Volume 23, Issue 12, Page(s) 842–856

Abstract: Forkhead box protein 3-expressing ( ... ...

Abstract	Forkhead box protein 3-expressing (FOXP3
MeSH term(s)	Humans ; T-Lymphocytes, Regulatory ; Gene Expression Regulation ; Cell Differentiation ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/metabolism ; Matrix Attachment Region Binding Proteins/genetics ; Matrix Attachment Region Binding Proteins/metabolism
Chemical Substances	Forkhead Transcription Factors ; SATB1 protein, human ; Matrix Attachment Region Binding Proteins
Language	English
Publishing date	2023-06-19
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2062776-2
ISSN	1474-1741 ; 1474-1733
ISSN (online)	1474-1741
ISSN	1474-1733
DOI	10.1038/s41577-023-00893-7
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Article ; Online: EBV-associated diseases: Current therapeutics and emerging technologies.

Chakravorty, Srishti / Afzali, Behdad / Kazemian, Majid

Frontiers in immunology

2022 Volume 13, Page(s) 1059133

Abstract: EBV is a prevalent virus, infecting >90% of the world's population. This is an oncogenic virus that causes ~200,000 cancer-related deaths annually. It is, in addition, a significant contributor to the burden of autoimmune diseases. Thus, EBV represents a ...

Abstract	EBV is a prevalent virus, infecting >90% of the world's population. This is an oncogenic virus that causes ~200,000 cancer-related deaths annually. It is, in addition, a significant contributor to the burden of autoimmune diseases. Thus, EBV represents a significant public health burden. Upon infection, EBV remains dormant in host cells for long periods of time. However, the presence or episodic reactivation of the virus increases the risk of transforming healthy cells to malignant cells that routinely escape host immune surveillance or of producing pathogenic autoantibodies. Cancers caused by EBV display distinct molecular behaviors compared to those of the same tissue type that are not caused by EBV, presenting opportunities for targeted treatments. Despite some encouraging results from exploration of vaccines, antiviral agents and immune- and cell-based treatments, the efficacy and safety of most therapeutics remain unclear. Here, we provide an up-to-date review focusing on underlying immune and environmental mechanisms, current therapeutics and vaccines, animal models and emerging technologies to study EBV-associated diseases that may help provide insights for the development of novel effective treatments.
MeSH term(s)	Animals ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections ; Immunologic Surveillance ; Autoimmune Diseases/therapy ; Autoimmune Diseases/complications ; Neoplasms/complications
Language	English
Publishing date	2022-10-27
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.1059133
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Article ; Online: CRM Discovery Beyond Model Insects.

Kazemian, Majid / Halfon, Marc S

Methods in molecular biology (Clifton, N.J.)

2018 Volume 1858, Page(s) 117–139

Abstract: Although the number of sequenced insect genomes numbers in the hundreds, little is known about gene regulatory sequences in any species other than the well-studied Drosophila melanogaster. We provide here a detailed protocol for using SCRMshaw, a ... ...

Abstract	Although the number of sequenced insect genomes numbers in the hundreds, little is known about gene regulatory sequences in any species other than the well-studied Drosophila melanogaster. We provide here a detailed protocol for using SCRMshaw, a computational method for predicting cis-regulatory modules (CRMs, also "enhancers") in sequenced insect genomes. SCRMshaw is effective for CRM discovery throughout the range of holometabolous insects and potentially in even more diverged species, with true-positive prediction rates of 75% or better. Minimal requirements for using SCRMshaw are a genome sequence and training data in the form of known Drosophila CRMs; a comprehensive set of the latter can be obtained from the SCRMshaw download site. For basic applications, a user with only modest computational know-how can run SCRMshaw on a desktop computer. SCRMshaw can be run with a single, narrow set of training data to predict CRMs regulating a specific pattern of gene expression, or with multiple sets of training data covering a broad range of CRM activities to provide an initial rough regulatory annotation of a complete, newly-sequenced genome.
MeSH term(s)	Animals ; Computational Biology/methods ; DNA/analysis ; DNA/genetics ; Genome, Insect ; High-Throughput Nucleotide Sequencing/methods ; Insect Proteins/genetics ; Insecta/genetics ; Regulatory Sequences, Nucleic Acid ; Sequence Analysis, DNA/methods
Chemical Substances	Insect Proteins ; DNA (9007-49-2)
Language	English
Publishing date	2018-11-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-8775-7_10
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Article ; Online: Non-coding RNAs in immunoregulation and autoimmunity: Technological advances and critical limitations.

Kumar, Dhaneshwar / Sahoo, Subhransu Sekhar / Chauss, Daniel / Kazemian, Majid / Afzali, Behdad

Journal of autoimmunity

2022 Volume 134, Page(s) 102982

Abstract: Immune cell function is critically dependent on precise control over transcriptional output from the genome. In this respect, integration of environmental signals that regulate gene expression, specifically by transcription factors, enhancer DNA elements, ...

Abstract	Immune cell function is critically dependent on precise control over transcriptional output from the genome. In this respect, integration of environmental signals that regulate gene expression, specifically by transcription factors, enhancer DNA elements, genome topography and non-coding RNAs (ncRNAs), are key components. The first three have been extensively investigated. Even though non-coding RNAs represent the vast majority of cellular RNA species, this class of RNA remains historically understudied. This is partly because of a lag in technological and bioinformatic innovations specifically capable of identifying and accurately measuring their expression. Nevertheless, recent progress in this domain has enabled a profusion of publications identifying novel sub-types of ncRNAs and studies directly addressing the function of ncRNAs in human health and disease. Many ncRNAs, including circular and enhancer RNAs, have now been demonstrated to play key functions in the regulation of immune cells and to show associations with immune-mediated diseases. Some ncRNAs may function as biomarkers of disease, aiding in diagnostics and in estimating response to treatment, while others may play a direct role in the pathogenesis of disease. Importantly, some are relatively stable and are amenable to therapeutic targeting, for example through gene therapy. Here, we provide an overview of ncRNAs and review technological advances that enable their study and hold substantial promise for the future. We provide context-specific examples by examining the associations of ncRNAs with four prototypical human autoimmune diseases, specifically rheumatoid arthritis, psoriasis, inflammatory bowel disease and multiple sclerosis. We anticipate that the utility and mechanistic roles of these ncRNAs in autoimmunity will be further elucidated in the near future.
MeSH term(s)	Humans ; Autoimmunity/genetics ; RNA, Untranslated/genetics ; RNA, Untranslated/metabolism ; Autoimmune Diseases/diagnosis ; Autoimmune Diseases/genetics ; Arthritis, Rheumatoid ; Multiple Sclerosis
Chemical Substances	RNA, Untranslated
Language	English
Publishing date	2022-12-31
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Intramural ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639452-8
ISSN	1095-9157 ; 0896-8411
ISSN (online)	1095-9157
ISSN	0896-8411
DOI	10.1016/j.jaut.2022.102982
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Article ; Online: Tox induces T cell IL-10 production in a BATF-dependent manner.

Canaria, D Alejandro / Rodriguez, J Alejandra / Wang, Luopin / Yeo, Franklin J / Yan, Bingyu / Wang, Mengbo / Campbell, Charlotte / Kazemian, Majid / Olson, Matthew R

Frontiers in immunology

2023 Volume 14, Page(s) 1275423

Abstract: Tox is a member of the high mobility group (HMG)-Box transcription factors and plays important roles in thymic T cell development. Outside of the thymus, however, Tox is also highly expressed by CD8 and CD4 T cells in various states of activation and in ... ...

Abstract	Tox is a member of the high mobility group (HMG)-Box transcription factors and plays important roles in thymic T cell development. Outside of the thymus, however, Tox is also highly expressed by CD8 and CD4 T cells in various states of activation and in settings of cancer and autoimmune disease. In CD4 T cells, Tox has been primarily studied in T follicular helper (TFH) cells where it, along with Tox2, promotes TFH differentiation by regulating key TFH-associated genes and suppressing CD4 cytotoxic T cell differentiation. However, the role of Tox in other T helper (Th) cell subtypes is less clear. Here, we show that Tox is expressed in several physiologically-activated Th subtypes and its ectopic expression enhances the
MeSH term(s)	Humans ; Basic-Leucine Zipper Transcription Factors/metabolism ; Interleukin-10/genetics ; Interleukin-10/metabolism ; T-Lymphocytes, Helper-Inducer ; Cell Differentiation ; Inflammation/metabolism
Chemical Substances	Basic-Leucine Zipper Transcription Factors ; Interleukin-10 (130068-27-8) ; BATF protein, human
Language	English
Publishing date	2023-11-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1275423
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Article ; Online: Kaposi's sarcoma herpesvirus latency-associated nuclear antigen broadly regulates viral gene expression and is essential for lytic infection.

Li, Shijun / Wang, Mengbo / Van Sciver, Nicholas / Szymula, Agnieszka / Tumuluri, Vinayak Sadasivam / George, Athira / Ramachandran, Akshaya / Raina, Komal / Costa, Catarina N / Zhao, Bo / Kazemian, Majid / Simas, J Pedro / Kaye, Kenneth M

PLoS pathogens

2024 Volume 20, Issue 1, Page(s) e1011907

Abstract: Kaposi's sarcoma herpesvirus (KSHV) is a leading cause of malignancy in AIDS and current therapies are limited. Like all herpesviruses, KSHV infection can be latent or lytic. KSHV latency-associated nuclear antigen (LANA) is essential for viral genome ... ...

Abstract	Kaposi's sarcoma herpesvirus (KSHV) is a leading cause of malignancy in AIDS and current therapies are limited. Like all herpesviruses, KSHV infection can be latent or lytic. KSHV latency-associated nuclear antigen (LANA) is essential for viral genome persistence during latent infection. LANA also maintains latency by antagonizing expression and function of the KSHV lytic switch protein, RTA. Here, we find LANA null KSHV is not capable of lytic replication, indicating a requirement for LANA. While LANA promoted both lytic and latent gene expression in cells partially permissive for lytic infection, it repressed expression in non-permissive cells. Importantly, forced RTA expression in non-permissive cells led to induction of lytic infection and LANA switched to promote, rather than repress, most lytic viral gene expression. When basal viral gene expression levels were high, LANA promoted expression, but repressed expression at low basal levels unless RTA expression was forcibly induced. LANA's effects were broad, but virus gene specific, extending to an engineered, recombinant viral GFP under control of host EF1α promoter, but not to host EF1α. Together, these results demonstrate that, in addition to its essential role in genome maintenance, LANA broadly regulates viral gene expression, and is required for high levels of lytic gene expression during lytic infection. Strategies that target LANA are expected to abolish KSHV infection.
MeSH term(s)	Humans ; Herpesvirus 8, Human/physiology ; Sarcoma, Kaposi ; Virus Latency/genetics ; Antigens, Viral/genetics ; Antigens, Viral/metabolism ; Gene Expression ; Gene Expression Regulation, Viral ; Virus Replication ; Nuclear Proteins
Chemical Substances	latency-associated nuclear antigen ; Antigens, Viral ; Nuclear Proteins
Language	English
Publishing date	2024-01-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1011907
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Article ; Online: The cytoplasmic LSm1-7 and nuclear LSm2-8 complexes exert opposite effects on Hepatitis B virus biosynthesis and interferon responses.

Rahman, Naimur / Sun, Jiazeng / Li, Zhili / Pattnaik, Aryamav / Mohallem, Rodrigo / Wang, Mengbo / Kazemian, Majid / Aryal, Uma K / Andrisani, Ourania

Frontiers in immunology

2022 Volume 13, Page(s) 970130

Abstract: Despite many studies on host or viral gene expression, how the cellular proteome responds to internal or external cues during the infection process remains unclear. In this study, we used a Hepatitis B Virus (HBV) replication model and performed ... ...

Abstract	Despite many studies on host or viral gene expression, how the cellular proteome responds to internal or external cues during the infection process remains unclear. In this study, we used a Hepatitis B Virus (HBV) replication model and performed proteomic analyses to understand how HBV evades innate immunity as a function of cell cycle progression. Specifically, we performed proteomic analyses of HBV-replicating cells in G1/S and G2/M phases, as a function of IFN-α treatment. We identified that the conserved LSm (Like-Sm1-8) proteins were differentially regulated in HBV replicating cells treated with IFN-α. Specifically, in G2/M phase, IFN-α increased protein level of LSm1, the unique subunit of cytoplasmic LSm1-7 complex involved in mRNA decay. By contrast, IFN-α decreased LSm8, the unique subunit of nuclear LSm2-8 complex, a chaperone of U6 spliceosomal RNA, suggesting the cytoplasmic LSm1-7 complex is antiviral, whereas the nuclear LSm2-8 complex is pro-viral. In HBV replication and infection models, siRNA-mediated knockdown of LSm1 increased all viral RNAs. Conversely, LSm8 knockdown reduced viral RNA levels, dependent on
MeSH term(s)	Antiviral Agents/pharmacology ; Hepatitis B virus/physiology ; Interferon-alpha/metabolism ; Proteomics ; RNA, Viral/genetics ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism
Chemical Substances	Antiviral Agents ; Interferon-alpha ; RNA, Viral ; RNA-Binding Proteins
Language	English
Publishing date	2022-08-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.970130
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Article ; Online: Combined Electrochemical, XPS, and STXM Study of Lithium Nitride as a Protective Coating for Lithium Metal and Lithium-Sulfur Batteries.

Fitch, Samuel D S / Moehl, Gilles E / Meddings, Nina / Fop, Sacha / Soulé, Samantha / Lee, Tien-Lin / Kazemian, Majid / Garcia-Araez, Nuria / Hector, Andrew L

ACS applied materials & interfaces

2023 Volume 15, Issue 33, Page(s) 39198–39210

Abstract: ... ...

Abstract	Li
Language	English
Publishing date	2023-08-08
Publishing country	United States
Document type	Journal Article
ISSN	1944-8252
ISSN (online)	1944-8252
DOI	10.1021/acsami.3c04897
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Article ; Online: RNA helicase DDX5 modulates sorafenib sensitivity in hepatocellular carcinoma via the Wnt/β-catenin-ferroptosis axis.

Li, Zhili / Caron de Fromentel, Claude / Kim, Woojun / Wang, Wen-Hung / Sun, Jiazeng / Yan, Bingyu / Utturkar, Sagar / Lanman, Nadia Atallah / Elzey, Bennett D / Yeo, Yoon / Zhang, Hao / Kazemian, Majid / Levrero, Massimo / Andrisani, Ourania

Cell death & disease

2023 Volume 14, Issue 11, Page(s) 786

Abstract: Reduced expression of the RNA helicase DDX5 associated with increased hepatocellular carcinoma (HCC) tumor grade and poor patient survival following treatment with sorafenib. While immunotherapy is the first-line treatment for HCC, sorafenib and other ... ...

Abstract	Reduced expression of the RNA helicase DDX5 associated with increased hepatocellular carcinoma (HCC) tumor grade and poor patient survival following treatment with sorafenib. While immunotherapy is the first-line treatment for HCC, sorafenib and other multi-tyrosine kinase inhibitors (mTKIs) are widely used when immunotherapy is contra-indicated or fails. Herein, we elucidate the role of DDX5 in sensitizing HCC to sorafenib, offering new therapeutic strategies. Treatment of various human HCC cell lines with sorafenib/mTKIs downregulated DDX5 in vitro and in preclinical HCC models. Conversely, DDX5 overexpression reduced the viability of sorafenib-treated cells via ferroptosis, suggesting a role for DDX5 in sorafenib sensitivity. RNAseq of wild-type vs. DDX5-knockdown cells treated with or without sorafenib identified a set of common genes repressed by DDX5 and upregulated by sorafenib. This set significantly overlaps with Wnt signaling genes, including Disheveled-1 (DVL1), an indispensable Wnt activator and prognostic indicator of poor survival for sorafenib-treated patients. DDX5-knockout (DDX5
MeSH term(s)	Humans ; Carcinoma, Hepatocellular/drug therapy ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/metabolism ; Sorafenib/pharmacology ; Sorafenib/therapeutic use ; Liver Neoplasms/drug therapy ; Liver Neoplasms/genetics ; Liver Neoplasms/metabolism ; Ferroptosis ; RNA Helicases/metabolism ; beta Catenin/metabolism ; Cell Line, Tumor ; Wnt Signaling Pathway
Chemical Substances	Sorafenib (9ZOQ3TZI87) ; RNA Helicases (EC 3.6.4.13) ; beta Catenin
Language	English
Publishing date	2023-11-30
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-023-06302-0
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Article ; Online: Importance of inner-sphere P-O-Fe bonds in natural and synthetic mineral-organic associations.

Eusterhues, Karin / Thieme, Jürgen / Narvekar, Sneha / Araki, Tohru / Kazemian, Majid / Kaulich, Burkhard / Regier, Tom / Wang, Jian / Lugmeier, Johann / Höschen, Carmen / Mansfeldt, Tim / Totsche, Kai Uwe

The Science of the total environment

2023 Volume 905, Page(s) 167232

Abstract: Sorption of organic molecules on mineral surfaces can occur through several binding mechanisms of varying strength. Here, we investigated the importance of inner-sphere P-O-Fe bonds in synthetic and natural mineral-organic associations. Natural organic ... ...

Abstract	Sorption of organic molecules on mineral surfaces can occur through several binding mechanisms of varying strength. Here, we investigated the importance of inner-sphere P-O-Fe bonds in synthetic and natural mineral-organic associations. Natural organic matter such as water extracted soil organic matter (WESOM) and extracellular polymeric substances (EPS) from liquid bacterial cultures were adsorbed to goethite and examined by FTIR spectroscopy and P K-edge NEXAFS spectroscopy. Natural particles from a Bg soil horizon (Gleysol) were subjected to X-ray fluorescence (XRF) mapping, NanoSIMS imaging, and NEXAFS spectro-microscopy at the P K-edge. Inner-sphere P-O-Fe bonds were identified for both, adsorbed EPS extracts and adsorbed WESOMs. Characteristic infrared peaks for P-O-Fe stretching vibrations are present but cannot unambiguously be interpreted due to possible interferences with mono- and polysaccharides. For the Bg horizon, P was only found on Fe oxides, covering the entire surface at different concentrations, but not on clay minerals. Linear combination fitting of NEXAFS spectra indicates that this adsorbed P is mainly a mixture of orthophosphate and organic P compounds. By combining atomic force microscopy (AFM) images with STXM-generated C and Fe distribution maps, we show that the Fe oxide surfaces were fully coated with organic matter. In contrast, clay minerals revealed a much lower C signal. The C NEXAFS spectra taken on the Fe oxides had a substantial contribution of carboxylic C, aliphatic C, and O-alkyl C, which is a composition clearly different from pure adsorbed EPS or aromatic-rich lignin-derived compounds. Our data show that inner-sphere P-O-Fe bonds are important for the association of Fe oxides with soil organic matter. In the Bg horizon, carboxyl groups and orthophosphate compete with the organic P compounds for adsorption sites.
Language	English
Publishing date	2023-09-19
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	121506-1
ISSN	1879-1026 ; 0048-9697
ISSN (online)	1879-1026
ISSN	0048-9697
DOI	10.1016/j.scitotenv.2023.167232
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