Sushmita Jha

• M.Sc, PhD
• Professor at Indian Institute of Technology Jodhpur

Glioblastoma (GBM) is the deadliest malignant brain tumor, with a survival of less than 14 months after diagnosis. The highly invasive nature of GBM makes total surgical resection challenging, leading to tumor recurrence and declined survival. The heterocellular composition of the GBM reprograms its microenvironment, favoring tumor growth, prolifer...

Glioblastoma (GBM) are malignant gliomas with an average survival of less than 14 months after diagnosis, despite surgery, chemotherapy, and radiotherapy. Tumor survival is aided by the heterogeneous cell populations in the tumor microenvironment. Two crucial innate immune cells of the brain, namely microglia and macrophages, favor a tumor-promotin...

Gliomas are primary brain tumors that develop from glial cells within the central nervous system (CNS) and are among the deadliest human cancers. Glioblastoma (GBM) is the most aggressive glioma. Innate immune cells such as microglia and macrophages account for >50% of the cellular population within the GBM microenvironment. Innate immune cells exp...

Gliomas are primary brain tumors that develop from glial cells within the central nervous system and are among the deadliest human cancers. Glioblastoma (GBM) is the most malignant form of glioma. NLRX1 is an innate immune pattern recognition receptor that exhibits tumor-suppressive and tumor-promoting effects that may be cancer or cell-type, conte...

Glioblastoma (GBM) is one of the most lethal malignancies in humans. Even after surgical resection and aggressive radio‐ or chemotherapies, patients with GBM can survive for less than 14 months. Extreme inter‐tumor and intra‐tumor heterogeneity of GBM poses a challenge for resolving recalcitrant GBM pathophysiology. GBM tumor microenvironment (TME)...

The mammalian NLR gene family was first reported over 20 years ago, although several genes that were later grouped into the family were already known at that time. Although it is widely known that NLRs include inflammasome receptors and/or sensors that promote the maturation of caspase 1, IL-1β, IL-18 and gasdermin D to drive inflammation and cell...

Inflammasomes are multiprotein complexes assembled in response to pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) and cellular stress. Inflammasome assembly is central to the maturation and secretion of proinflammatory cytokines and cell death pathways. This chapter highlights the organization of NLRP3, NLRC4/NAIP, NLRP1, and A...

Extracellular traps (ETs) are composed of decondensed chromatin and are embedded with various antimicrobial proteins like myeloperoxidase and histones. Recently, we reported that dopamine (DA) induces ETs in BV2 microglia cell line and primary adult human microglia in a manner independent of cell death, reactive oxygen species, and actin polymeriza...

Dopamine (DA) is central to neurological functions like motivation, movement and reward (Klein et al. 2019). While its role in diseases like Parkinson’s, Alzheimer’s and schizophrenia are well studied, its role in regulating immune functions have just started to unfold. DA receptors are present on almost all immune cells and they regulate innate an...

Gliomas are the most prevalent primary brain tumors with immense clinical heterogeneity, poor prognosis and survival. Gliomas arise from glial cells and are heavily infiltrated with innate immune cells. In India high-grade gliomas or Glioblastomas (GBM) account for 59.5% of CNS tumours. A key challenge for clinical management of GBM is its highly h...

Dopamine (DA) plays many roles in the brain, especially in movement, motivation, and reinforcement of behavior; however, its role in regulating innate immunity is not clear. Here, we show that DA can induce DNA-based extracellular traps in primary, adult, human microglia and BV2 microglia cell line. These DNA-based extracellular traps are formed in...

Microglia are resident innate immune cells of the central nervous system (CNS). Microglia play a critical role during development, in maintaining homeostasis, and during infection or injury. Several independent research groups have highlighted the central role that microglia play in autoimmune diseases, autoinflammatory syndromes and cancers. The a...

NeuroscienceObtaining Human Microglia from Adult Human Brain Tissue doi: 10.3791/61438 Published: August 30, 2020 DOI Ishan Agrawal1, Shivanjali Saxena1, Preethika Nair1, Deepak Jha2, Sushmita Jha1 1Department of Bioscience and Bioengineering, Indian Institute of Technology Jodhpur, 2Department of Neurosurgery, All India Institute of Medical Sci...

In 1907, Alois Alzheimer observed, as he quoted, development of “numerous fibers” and “adipose saccules” in the brain of his diseased patient Auguste Deter. The neurodegenerative disease became known as Alzheimer’s disease (AD) and is the most common cause of dementia worldwide. AD normally develops with aging and is mostly initiated because of the...

Nanoparticles are promising bioengineering platforms facilitating various consumer product formulations, including packaged food, electrical, biosensors and biomedical tools. The unique surface and physicochemical properties of amorphous nanosilica supports advanced nano-biomolecular applications for various manufacturing, biotechnology, and health...

Apoptosis associated speck like protein containing CARD (ASC) is widely researched and recognized as an adaptor protein participating in inflammasome assembly and pyroptosis. It contains a bipartite structure comprising of a pyrin and a caspase recruitment domain (CARD) domain. These two domains help ASC function as an adaptor molecule. ASC is enco...

Hypoxia is a pathological condition known to occur in several diseases including stroke and certain cancers. The development and testing of a portable hypoxia chamber remains a challenge. Hypoxia simulating devices typically consist of a sealed chamber that is placed inside the existing laboratory incubator at 37⁰ C. Existing devices for simulating...

Dopamine (DA) plays many roles in the brain, especially in movement, motivation, and reinforcement of behavior; however, its role in regulating innate immunity is not clear. Here, we show that DA can induce DNA-based extracellular traps in primary, adult, human microglia and BV2 microglia cell line. These DNA-based extracellular traps are formed in...

Gliomas are the most prevalent primary brain tumors with immense clinical heterogeneity, poor prognosis and survival. The nucleotide-binding domain, and leucine-rich repeat containing receptors (NLRs) and absent-in-melanoma 2 (AIM2) are innate immune receptors crucial for initiation and progression of several cancers. There is a dearth of reports l...

Nucleotide binding domain, leucine-rich repeat containing proteins (NLRs) are a family of pattern recognition receptors involved in major innate immune defense mechanisms. NLRs play a key role in several cancers, autoimmune, and inflammation-associated diseases. Association of NLRP3 has been widely investigated in neurodegenerative diseases, chroni...

Gliomas are the most common and challenging type of primary brain tumor with low prognosis and survival rate. Glioma accounts for ~80% of primary malignant brain tumors. Glioma tissues are heavily infiltrated by the innate immune cells. Despite of the dual tumor-promoting and -inhibitory roles of NLRs, their function in glioma remains unknown. Our...

Chitin membranes containing nanosilver were evaluated for use as antimicrobial wound dressings. Chitin at a concentration of 0.25% dissolved in 5% lithium chloride-dimethylacetamide and nanosilver synthesized by gamma irradiation were used for fabrication of chitin-nanosilver membranes. UV–vis spectroscopy and energy dispersive x-ray (EDX) analysis...

Gliomas are the most common and challenging type of primary brain tumor with low prognosis and survival rate. Glioma accounts for ~80% of primary malignant brain tumors. Glioma tissues are heavily infiltrated by the innate immune cells. Despite of the dual tumor-promoting and-inhibitory roles of NLRs, their function in glioma remains unknown. Our s...

The inflammasome is implicated in many inflammatory diseases including neurological diseases but has been primarily studied in the macrophage-myeloid lineage. Here we demonstrate a physiologic role for nucleotide-binding domain, leucine-rich repeat, CARD domain containing proteins, NLRC4 and NLRP3, in brain astrocytes and microglia under the steril...

Inflammation in the brain accompanies several high-impact neurological diseases including multiple sclerosis (MS), stroke, and Alzheimer's disease. Neuroinflammation is sterile, as damage-associated molecular patterns rather than microbial pathogens elicit the response. The inflammasome, which leads to caspase-1 activation, is implicated in neuroin...

Trigonella foenum-graecum (fenugreek) is an important medicinal plant, well known for its anti-inflammatory properties. However, the underlying cellular and molecular mechanisms of its action remain largely unknown. The apoptosis associated speck like protein containing a caspase recruitment domain (CARD) (ASC) is central to inflammatory and cell d...

NLRs (nucleotide-binding domain and leucine-rich repeats containing receptors) are pattern recognition receptors, evolutionarily conserved across plants and animals (1). NLRs, initiate immune response against specific damage and pathogen-associated molecular patterns (DAMPs/PAMPs) (2). NLRs also contribute to the function and regulation of multiple...

Inflammasomes in Myeloid Cells: Warriors Within, Page 1 of 2 Abstract The inflammasome is a large multimeric protein complex comprising an effector protein that demonstrates specificity for a variety of activators or ligands; an adaptor molecule; and procaspase-1, which is converted to caspase-1 upon inflammasome activation. Inflammasomes are exp...

Trigonella foenum-graecum (fenugreek) is an important medicinal plant, well known for its anti-inflammatory properties. However, the underlying cellular and molecular mechanisms of its action remain largely unknown. The apoptosis associated speck like protein containing a caspase recruitment domain (CARD) (ASC) is central to inflammatory and cell d...

NLRs (nucleotide-binding domain, leucine-rich repeat containing receptors) are pattern recognition receptors associated with immunity and inflammation in response to endogenous and exogenous pathogen and damage associated molecular patterns (PAMPs and DAMPs respectively). Dysregulated NLR function is associated with several diseases including cance...

Inflammation is a double-edged sword. While short-lived, acute inflammation is essential for the repair and resolution of infection and damage, uncontrolled and unresolved chronic inflammation is central to several diseases, including cancer, autoimmune diseases, allergy, metabolic disease, and cardiovascular disease. This report aims to review the...

Exploring the symbiotic nature of biological systems can result in valuable knowledge for computer networks. Biologically inspired approaches to security in networks are interesting to evaluate because of the analogies between network security and survival of human body under pathogenic attacks. Wireless Sensor Network (WSN) is a network based on m...

Exploring the symbiotic nature of biological systems can result in valuable knowledge for computer networks. Biologically inspired approaches to security in networks are interesting to evaluate because of the analogies between network security and survival of human body under pathogenic attacks. Wireless Sensor Network (WSN) is a network based on m...

The role of innate immune regulators is investigated in injury sustained from irradiation as in the clinic for cancer treatment or from a nuclear incident. The protective benefits of flagellin signaling through Toll-like receptors (TLR) in an irradiation setting warrant study of a key intracellular adaptor of TLR signaling, namely Myeloid different...

Live cell video of cell motility of wild type, M-CSF treated macrophages. Representative cell movement videos over a 2.5 hour time period. 1×104 cells were plated on glass bottom dishes (MatTek Ashland, MA P35G-1.5-10-C) in complete DMEM, rested overnight, and treated with 50 ng/ml M-CSF in warmed DMEM. Cells were imaged on a Nikon Biostation (Belm...

Live cell video of cell motility of wild type macrophages. Representative cell movement videos over a 2.5 hour time period. 1×104 cells were plated on glass bottom dishes (MatTek Ashland, MA P35G-1.5-10-C) in complete DMEM, rested overnight, and treated with sham (warmed DMEM). Cells were imaged on a Nikon Biostation (Belmont, CA) with a 20× object...

Live cell video of cell motility of Plxnb2−/− macrophages. Representative cell movement video over a 2.5 hour time period. 1×104 cells were plated on glass bottom dishes (MatTek Ashland, MA P35G-1.5-10-C) in complete DMEM, rested overnight, and treated with sham (warmed DMEM). Cells were imaged on a Nikon Biostation (Belmont, CA) with a 20× objecti...

Macrophage marker F4/80 is expressed by bone marrow derived wild type and Plxnb2−/− macrophages. Flow cytometry plot of A) Plxnb2−/− and B) wild type bone marrow derived macrophages. Bone marrow cells were plated on plastic plates and grown in complete DMEM and L929 media. Cells were harvested, blocked, and stained with antibody against F4/80 and P...

Semaphorin 4C is expressed in the human and mouse immune system. cDNA expression level of in A) mouse and B) human immune cells from BioGPS database [37]. (EPS)

Live cell videos of in vitro wound closure of wild type macrophages. Representative live cell imaging of wound healing assay with wild type macrophages. 1×106 cells were plated on 12 well glass or plastic plates in complete DMEM and rested overnight. An artificial wound was introduced using a 200 ul pipette tip, and cells were imaged closing the wo...

Live cell videos of in vitro wound closure of Plxnb2−/− macrophages. Representative live cell imaging of wound healing assay with Plxnb2−/− macrophages. 1×106 cells were plated on 12 well glass or plastic plates in complete DMEM and rested overnight. An artificial wound was introduced using a 200 ul pipette tip, and cells were imaged closing the wo...

Live cell video of cell motility of Plxnb2−/−, M-CSF treated macrophages. Representative cell movement videos over a 2.5 hour time period. 1×104 cells were plated on glass bottom dishes (MatTek Ashland, MA P35G-1.5-10-C) in complete DMEM, rested overnight, and treated with 50 ng/ml M-CSF in warmed DMEM. Cells were imaged on a Nikon Biostation (Belm...

Plexins are cell surface receptors widely studied in the nervous system, where they mediate migration and morphogenesis though the Rho family of small GTPases. More recently, plexins have been implicated in immune processes including cell-cell interaction, immune activation, migration, and cytokine production. Plexin-B2 facilitates ligand induced c...

High-fat diet (HFD) and inflammation are key contributors to insulin resistance and type 2 diabetes (T2D). Interleukin (IL)-1β plays a role in insulin resistance, yet how IL-1β is induced by the fatty acids in an HFD, and how this alters insulin signaling, is unclear. We show that the saturated fatty acid palmitate, but not unsaturated oleate, indu...

Long-lived humoral immune responses depend upon the generation of memory B cells and long-lived plasma cells during the germinal center (GC) reaction. These memory compartments, characterized by class-switched IgG and high-affinity Abs, are the basis for successful vaccination. We report that a new member of the plexin family of molecules, plexin-D...

To investigate the role of recombinant human interleukin-11 (rhIL-11) on in vivo mobilization of CD34(+)/vascular endothelial growth factor receptor (VEGFR) 2(+) mononuclear cells and collateral vessel remodeling in a mouse model of hindlimb ischemia. We observed that treatment of Sv129 mice with continuous infusion of 200-μg/kg rhIL-11 per day led...

Inflammation is increasingly recognized as an important contributor to a host of CNS disorders; however, its regulation in the brain is not well delineated. Nucleotide-binding domain, leucine-rich repeat, pyrin domain containing 3 (NLRP3) is a key component of the inflammasome complex, which also includes ASC (apoptotic speck-containing protein wit...

The nucleotide-binding domain, leucine-rich repeat (NLR) proteins are a recently discovered family of intracellular pathogen and danger signal sensors. NLRs have emerged as important contributors to innate immunity in animals. The physiological impact of these genes is increasingly evident, underscored by the genetic association of variant family m...