Review
Pharmacology & Pharmacy
Yuhan Su, Tianyu Tao, Xiuxing Liu, Wenru Su
Summary: This review summarizes the diverse roles of the JAK-STAT signaling pathway in ocular homeostasis and non-infectious uveitis (NIU) pathology, and discusses the safety and efficacy of JAK inhibitors for treating NIU and potential approaches for treatment optimization.
BIOCHEMICAL PHARMACOLOGY
(2022)
Review
Immunology
Xiaoxue Ma, Shingo Nakayamada
Summary: T follicular helper (Tfh) cells participate in humoral immune responses by promoting inflammation and aiding B cells survival, proliferation, maturation, and generation of autoantibodies. The plasticity of Tfh cells allows for adjustment of differentiation direction based on immune response level, regulated by various signaling factors such as cytokines, receptors, transcription factors, and genes. The STAT family signaling pathways play a crucial role in Tfh formation, with each member contributing to Tfh differentiation through mutual restraint and cooperation among cytokine-STAT signals.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Sunghark Kwon
Summary: JAKs are important enzymes in the JAK-STAT signaling pathway, and dysfunctional JAKs can lead to severe immune system-related diseases. Various JAK inhibitors have been developed to block abnormal JAK-STAT signaling, but drug selectivity and resistance to these inhibitors remain challenges. This review discusses the role and structure of JAKs, as well as strategies for disrupting JAK dimerization to develop novel inhibitors.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Benjawan Wudtiwai, Anupong Makeudom, Suttichai Krisanaprakornkit, Peraphan Pothacharoen, Prachya Kongtawelert
Summary: The study demonstrates that hesperidin effectively reduces cell proliferation and migration of oral cancer cells by inhibiting PD-L1 expression and inactivating STAT1 and STAT3 signaling molecules. This suggests hesperidin could be a potential adjunctive treatment for oral cancer.
Article
Dentistry, Oral Surgery & Medicine
Kie Nakatani, Satoshi Serada, Minoru Fujimoto, Kengo Obata, Tomoharu Ohkawara, Eri Sasabe, Tetsuya Yamamoto, Tetsuji Naka
Summary: The study revealed that SOCS1 gene therapy has anti-tumor effects on oral squamous cell carcinoma, inducing apoptosis through regulating the JAK/STAT-independent pathway. Overexpression of SOCS1 inhibited the JAK/STAT and p44/42 MAPK pathways, decreased Mcl-1 expression, and suppressed proliferation of OSCC cells.
JOURNAL OF ORAL PATHOLOGY & MEDICINE
(2022)
Article
Dermatology
James G. Krueger, Iain B. McInnes, Andrew Blauvelt
Summary: Plaque psoriasis is a common, chronic, systemic, immune-mediated inflammatory disease. The Janus kinase-signal transducer and activator of transcription pathway plays a major role in psoriasis, but safety concerns persist with current JAK inhibitors. TYK2, a member of the JAK family, may offer a potential target for safer and more effective therapies in psoriasis treatment.
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
(2022)
Review
Immunology
Amr Allam, Marina Yakou, Lokman Pang, Matthias Ernst, Jennifer Huynh
Summary: This article discusses the relationship between cancer-associated fibroblasts (CAFs) and signal transducer and activator of transcription 3 (STAT3) in the tumor microenvironment, as well as their impact on tumor growth, immune suppression, and metastatic spread. Research suggests that CAF-intrinsic STAT3 activity is closely associated with tumor progression.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ji-Rong Xie, Xiao-Jie Chen, Gang Zhou
Summary: Nuciferine shows potential as a therapeutic agent for oral squamous cell carcinoma (OSCC) by inhibiting cell growth and infiltration, and suppressing the STAT3 signaling pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Lena Puigdevall, Camille Michiels, Clara Stewardson, Laure Dumoutier
Summary: A subset of cytokines triggers the JAK-STAT pathway to exert various functions such as inflammation and immune responses. There are alternative modes of STAT activation, including association between the tyrosine-free region of cytokine receptors and STATs, and direct interaction between JAK and STAT proteins. These noncanonical mechanisms by cytokine receptors suggest their importance and are discussed in this review.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2022)
Article
Multidisciplinary Sciences
Supranee Buranapraditkun, Patnarin Mahattanasakul, Areeya Diloktaweewattana, Narumol Bhummaphan, Chutha Siriwattanakankul, Fardeela Bin-Alee, Napadon Tangjaturonrasme, Apiwat Mutirangura, Nakarin Kitkumthorn
Summary: This study found that plasma levels of IL-6, 4-1BB, PDL-1, PD-1, and CTLA-4 were increased, while IL-13 and sCD27 levels were decreased in patients with oral and oropharyngeal cancer, particularly in those in stage IV.
Article
Biochemistry & Molecular Biology
Haowei Cai, Zhuorong Liu, Ping Sun, Yinghua Zhou, Yuyun Yan, Yiming Luo, Xiuxiu Zhang, Ruiwen Wu, Xiangting Liang, Dan Wu, Wenhui Hu, Zhongjin Yang
Summary: This study describes the discovery of a novel inhibitor, 10v, that can block both inflammasome/IL-1β signaling and decrease the expression of STAT1 and STAT5 in the JAK/STAT pathway. In a mouse model of colitis, 10v exhibits significant anti-IL-1β effect and reduces the levels of STAT1 and STAT5. This finding offers a new therapeutic strategy for IBD patients who do not respond to conventional drug therapy.
RSC MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Peng He, Ying Miao, Yue Sun, Aiwu Bian, Wangrui Jin, Jiangnan Ye, Huang Chen, Jia He, Yangrui Peng, Haijun Gu, Mingyao Liu, Zhengfang Yi, Yihua Chen
Summary: This study describes the design, synthesis, and structure-activity relationship studies of triaromatic heterocyclic derivatives as potent dual phosphorylation STAT3 inhibitors. The best compound 3h (HP590) was discovered with high inhibitory activity against p-Tyr(705) and p-Ser(727), resulting in the growth inhibition of gastric cancer both in vitro and in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Feng Zhou, Fanyun Zhu, Tianru Zhu, Zhucheng Zhao, Luyao Li, Shichong Lin, Haiyang Zhao, Lehe Yang, Chengguang Zhao, Liangxing Wang, Jifa Li, Xiaoying Huang
Summary: AT7519, a CDK inhibitor, exhibits great anti-tumor effects in lung cancer by blocking IL-6/STAT3 pathway and inhibiting cell proliferation and inducing apoptosis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Ru Wang, Ting-Ting Du, Wen-Qiang Liu, Yi-Chen Liu, Ya-Dong Yang, Jin-Ping Hu, Ming Ji, Bei-Bei Yang, Li Li, Xiao-Guang Chen
Summary: By designing and testing the inhibitory effects of compounds on the STAT3 pathway, researchers have successfully developed a novel selective STAT3 inhibitor that can inhibit STAT3 phosphorylation, translocation, and downstream gene transcription. This compound has demonstrated anti-proliferative and apoptotic effects on STAT3-overactivated cancer cells and exhibited promising anti-tumor efficacy in a mouse model.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Huang Chen, Aiwu Bian, Lian-fang Yang, Xuan Yin, Jie Wang, Chaowen Ti, Ying Miao, Shihong Peng, Shifen Xu, Mingyao Liu, Wen-Wei Qiu, Zhengfang Yi
Summary: A new small-molecule inhibitor N4 shows potent anti-tumor bioactivity in pancreatic cancer by targeting STAT3, effectively suppressing tumor growth and metastasis, and potentially offering clinical benefits for treatment.
Review
Biochemistry & Molecular Biology
Thalia Pacheco-Fernandez, Greta Volpedo, Chaitenya Verma, Abhay R. Satoskar
Summary: Leishmaniasis is a neglected tropical disease transmitted by sand flies and manifests clinically in various forms. Host immune responses are critical in fighting against the disease, but Leishmania parasites manipulate these responses for their own survival. Factors like sand fly salivary proteins and microbiota also influence disease susceptibility.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2021)
Article
Cell Biology
N. Fatima, N. Sheikh, A. R. Satoskar, T. Akhtar, A. Tayyeb, I Ashfaq, N. Ryan, S. Ambreen, B. K. Jha, S. Oghumu
Summary: The study revealed that even short-term exposure to tacrolimus (TAC) can induce changes in antioxidant status and lipid peroxidation in the liver of rats, leading to significant alterations in liver structure and increased inflammatory response.
MEDIATORS OF INFLAMMATION
(2021)
Article
Oncology
Kelvin Anderson, Nathan Ryan, Anastasia Alkhimovitch, Arham Siddiqui, Steve Oghumu
Summary: Inhibition of PI3K p110 gamma may enhance the anti-tumor immune response against poorly immunogenic HNSCC, particularly when used in combination with selective checkpoint inhibitors.
Review
Immunology
Thalia Pacheco-Fernandez, Greta Volpedo, Sreenivas Gannavaram, Parna Bhattacharya, Ranadhir Dey, Abhay Satoskar, Greg Matlashewski, Hira L. Nakhasi
Summary: Leishmaniasis is a disease caused by parasitic protozoa transmitted by infected sandflies, affecting over 1 billion people worldwide. The successful vaccination procedure known as leishmanization, which has been used in the Middle East for decades, is no longer practiced due to safety and ethical concerns. New genome editing technologies may allow for the development of a second generation leishmanization that could enter human trials.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Parasitology
Nargis Shaheen, Chaitenya Verma, Thalia Pacheco-Fernandez, Greta Volpedo, Aneeqa Hamid, Ismail Zeb, Syed Aizaz Ali Shah, Shah Fahad, Attiya Iqbal, Asma Ashraf, Amjad Khan, Misbah Gul, Muhammad Ilyas Khan, Huma Fatima, Muhammad Afzal, Abhay R. Satoskar, Naveeda Akhter Qureshi
Summary: This study aimed to elucidate the molecular characterization and genetic diversity of Leishmania spp. in North Eastern Pakistan. The findings confirmed the presence of Leishmania tropica, Leishmania major, and Leishmania infantum, with Leishmania tropica showing significantly higher nucleotide variation. Recommendations for more extensive investigations to understand the molecular epidemiology of Leishmania in the region were made.
Review
Immunology
Greta Volpedo, Ryan H. Huston, Erin A. Holcomb, Thalia Pacheco-Fernandez, Sreenivas Gannavaram, Parna Bhattacharya, Hira L. Nakhasi, Abhay R. Satoskar
Summary: Leishmaniasis is a significant public health issue globally, requiring effective vaccines for prevention and control. The disease leads to long-term disabilities, psycho-sociological trauma, poverty, and gender disparity. Challenges in research include manufacturing vaccines, conducting clinical trials, and defining correlates of protection.
EXPERT REVIEW OF VACCINES
(2021)
Review
Immunology
Greta Volpedo, Thalia Pacheco-Fernandez, Erin A. Holcomb, Natalie Cipriano, Blake Cox, Abhay R. Satoskar
Summary: Leishmaniasis is a neglected tropical disease affecting 12 million people worldwide. Cutaneous leishmaniasis (CL) is the most common form, presenting as ulcerating skin lesions that can self-heal or become chronic. The balance of immune response and inflammatory mediators plays a vital role in the clinical presentation and outcome of the disease.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biology
Subir Karmakar, Nevien Ismail, Fabiano Oliveira, James Oristian, Wen Wei Zhang, Swarnendu Kaviraj, Kamaleshwar P. Singh, Abhishek Mondal, Sushmita Das, Krishna Pandey, Parna Bhattacharya, Greta Volpedo, Sreenivas Gannavaram, Monika Satoskar, Sanika Satoskar, Rajiv M. Sastry, Claudio Meneses, Shinjiro Hamano, Pradeep Das, Greg Matlashewski, Sanjay Singh, Shaden Kamhawi, Ranadhir Dey, Jesus G. Valenzuela, Abhay Satoskar, Hira L. Nakhasi
Summary: Karmakar et al. developed a dermotropic, live attenuated centrin gene-deleted Leishmania major (LmCen(-/-)) vaccine against Visceral Leishmaniasis (VL), demonstrating that a single intradermal injection provides robust and durable protection against lethal VL transmitted through sand fly bites.
COMMUNICATIONS BIOLOGY
(2021)
Review
Immunology
Greta Volpedo, Thalia Pacheco-Fernandez, Parna Bhattacharya, Timur Oljuskin, Ranadhir Dey, Sreenivas Gannavaram, Abhay R. Satoskar, Hira L. Nakhasi
Summary: Leishmaniasis is a disease endemic in tropical and subtropical regions transmitted by infected sand flies. The interactions between Leishmania, host immune cells, and adaptive immunity play a crucial role in disease severity and development. Besides cytokine signals, metabolic shifts in innate cells also influence immune signaling cascades in Leishmania pathogenesis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Greta Volpedo, Thalia Pacheco-Fernandez, Erin A. Holcomb, Wen-Wei Zhang, Patrick Lypaczewski, Blake Cox, Rebecca Fultz, Chelsea Mishan, Chaitenya Verma, Ryan H. Huston, Abigail R. Wharton, Ranadhir Dey, Subir Karmakar, Steve Oghumu, Shinjiro Hamano, Sreenivas Gannavaram, Hira L. Nakhasi, Greg Matlashewski, Abhay R. Satoskar
Summary: Using the CRISPR/Cas9 technique, researchers have successfully generated live attenuated centrin knockout L. mexicana parasites. These parasites exhibit a growth defect and lower parasitic burdens compared to the wild type, as well as increased production of protective cytokines. In pre-clinical models, immunization with the LmexCen(-/-) parasites is safe and efficacious, leading to protective immunity and reduced parasitic burdens at the infection site and draining lymph nodes.
Review
Microbiology
Greta Volpedo, Parna Bhattacharya, Sreenivas Gannavaram, Thalia Pacheco-Fernandez, Timur Oljuskin, Ranadhir Dey, Abhay R. Satoskar, Hira L. Nakhasi
Summary: Leishmaniasis is a neglected tropical disease that affects millions of people worldwide. Current treatments are not highly effective and have high costs and toxicity. The development of a prophylactic vaccine has become a high priority, but the ability of Leishmania to undermine immune recognition has hindered progress. Live attenuated Leishmania parasites that provide a complete range of antigens could be effective vaccine candidates. This review focuses on the development of live attenuated Leishmania vaccines and discusses the challenges of transitioning from the laboratory to human clinical trials.
Article
Biotechnology & Applied Microbiology
Felipe F. F. Lamenza, Nathan M. M. Ryan, Puja Upadhaya, Arham Siddiqui, Pete P. P. Jordanides, Anna Springer, Peyton Roth, Hasan Pracha, O. Hans Iwenofu, Steve Oghumu
Summary: Head and neck squamous cell carcinoma (HNSCC) is a significant public health problem. We optimized a mouse model of tongue carcinogenesis and found that dietary administration of black raspberries can reduce tumor growth and enhance anti-tumor activity.
CANCER GENE THERAPY
(2023)
Article
Immunology
Nebiye Yentur Doni, Paul J. Bertani, Greta Volpedo, Noushin Saljoughian, Sanjay Varikuti, Greg Matlashewski, Wu Lu, Abhay R. Satoskar
Summary: This article introduces the use of immuno field effect transistors (ImmunoFET) biosensors for monitoring and detecting Leishmania parasites. The current methods of leishmanial diagnosis are time-consuming, costly, and require special equipment and trained personnel. The study demonstrates that ImmunoFET biosensors can successfully detect the presence of Leishmania parasites and have the potential to provide earlier and faster detection of leishmaniasis compared to ELISA.
PARASITE IMMUNOLOGY
(2023)
Article
Oncology
Puja Upadhaya, Nathan Ryan, Peyton Roth, Travis Pero, Felipe Lamenza, Anna Springer, Pete Jordanides, Hasan Pracha, Darrion Mitchell, Steve Oghumu
Summary: This study demonstrates that tumor-targeted radiation therapy can generate tumor antigens that induce strong immune responses. These responses show comparable sensitivity but greater specificity for T cell activation compared to conventional antibodies. This information can be utilized to predict patient responses to radiation and immune therapy.
Meeting Abstract
Public, Environmental & Occupational Health
Subir Karmakar, Nevien Ismail, Wenwei Zhang, Oliveira Fabiano, Greta Volpedo, Shinjiro Hamano, Greg Matlashewski, Shaden Kamhawi, Jesus Valenzuela, Abhay Satoskar, Ranadhir Dey, Hira Nakhasi
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
(2021)