JAK-STAT Signaling in Diseases

291 Pages·2020·11.166 MB·\291

by  Ritobrata Goswami (Editor)

JAK-STAT Signaling in

Diseases

JAK-STAT Signaling in

Diseases

Edited by

Ritobrata Goswami
CRC Press
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Contents

Preface........................................................................................................................ vii

Editor.......................................................................................................................... ix

Contributors................................................................................................................. xi

1. Regulation of Cytokine Signaling by the JAK-STAT Pathway ...........................................1

Nicolette Nadene Houreld
2. The Structure-Function Bonhomie of JAK-STAT Molecules..............................................9

Ritobrata Goswami
3. MicroRNA-Mediated Regulation of JAK-STAT Signaling in Non-Cancerous

Human Diseases ..................................................................................................... 35

Chandra S. Boosani, Wanlin Jiang, Taylor Burke, and Devendra K. Agrawal
4. JAK-STAT Signaling in Asthma and Allergic Airway Inflammation.................................. 49

Amina Abdul Qayum, Tristan Hayes and Mark H. Kaplan
5. Role of JAK-STAT Signaling in Atopic Dermatitis........................................................ 69

Radomir M. Slominski and Matthew J. Turner
6. JAK-STAT Signaling Pathway and Gliosis in Neuroinflammatory Diseases........................ 83

Han-Chung Lee, Kai-Leng Tan, Pike-See Cheah and King-Hwa Ling
7. JAK-STAT Signaling in Cardiovascular Disease ..........................................................103

George W. Booz, Raffaele Altara and Sean P. Didion
8. Diabetes and Obesity: Abnormal JAK-STAT Signaling .................................................123

Marcia J. Abbott
9. JAK-STAT Signaling in Liver Fibrosis.......................................................................143

Marwa K. Ibrahim and Noha G. Bader El Din
10. Renal Disorders: Involvement of JAK-STAT Pathway...................................................159

Yuji Nozaki
11. JAK-STAT Signaling in Hematologic Malignancies .....................................................177

Thomas Pincez and Thai Hoa Tran
12. Aberrant JAK-STAT Signaling in Hematopoietic Malignancies ......................................225

Parvis Sadjadian
v
vi Contents
13. Immunodeficiency: Consequences of Mutations in JAK-STAT Signaling ...........................241

Daniel Silberger and Duy Pham
14. Targeting JAK-STAT Pathway for Various Inflammatory Diseases and

Viral Infections ......................................................................................................257

Christina Gavegnano and Raymond F. Schinazi
Index ..................................................................................................................269
Preface

JAK-STAT (Janus kinase-Signal Transducers and Activators of Transcription) signaling is one of
the few conserved signaling cascades transmitting multiple signals required for homeostasis in
animals and humans. In JAK-STAT signaling, extracellular ligand binding to its cognate receptor
leads to pathway activation and signal transduction. This pathway is critical for hematopoiesis,
immune system development, and other events. Activation of JAK leads to induction of cell
proliferation, cell migration, differentiation, and apoptosis. Mutations in JAK-STAT pathway can
either lead to inflammatory diseases or may impede regular homeostasis.
JAK-STAT pathways can cross-talk with other signaling pathways. JAK-STAT pathway has
been targeted to develop drugs to downregulate the immune response. Few of the JAK inhibitors
are in Phase III of clinical trial and have been approved by FDA. Tofacitinib that targets JAK3
has shown its effect to treat rheumatoid arthritis, psoriasis. OPB-51602, which targets STAT3, is
in phase I to treat nasopharyngeal carcinoma. JAK inhibitors have an advantage over cytokine
receptor blocking drugs in that they that can be taken orally as they are small molecule drugs.
JAK-STAT pathway is a very well-studied signaling pathway. The book has consolidated
information on the role of JAK-STAT signaling in autoimmune and inflammatory diseases
including asthma, atopic dermatitis, hepatic fibrosis, diabetes and obesity, cancer, cardiovascular
disease, immunodeficiency, renal disorders, neuro-inflammatory disorders, among others. This
book is unique as it encompasses different aspects of JAK-STAT signaling and how dysregulation
of this signaling pathway is associated with various disorders that are prevalent worldwide leading
to morbidity and mortality associated with increased expenditure on healthcare and loss of
manpower. This book has an update on the therapeutic implication of JAK-STAT inhibitors
different phases of clinical trial. I sincerely believe this book will stimulate interest in graduate
students, academicians and scientific community. This book will be good reference point for
industry professionals who are involved in translational research leading to develop products to
various diseases. Positive feedback of this book from the readers will allow us to expand the
disease repertoire that is associated with dysregulated JAK-STAT signaling.

Editor

Ritobrata Goswami, PhD, is presently working as an Assistant Professor in the
School of Bioscience, IIT Kharagpur since 2016. Prior to his present affiliation,
Dr Goswami was associated with the Division of Biological and Life Sciences,
Ahmedabad University (2014-16). He received his bachelor (2005) and mas­
ters’ degree (2007) in Biotechnology from West Bengal University of Tech­
nology and Birla Institute of Technology & Science, Pilani; respectively.
Dr Goswami obtained his PhD at Indiana University, Indianapolis, USA
(2012) followed by post-doctoral training at Icahn School of Medicine at
Mount Sinai, New York, USA (2012-14). He is a life member of the Indian
Immunology Society. Dr Goswami has extramural projects funded by the Government of India.
Dr Goswami’s research interests include the role of nutrients and hormones in the development
and function of T helper c ells to regulate inflammatory disorders. He is keen on identifying
a regulating network of transcription factors involved in autoimmune and inflammatory disorders so
that better therapeutics can be developed.
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