Mayank Srivastava

Verified

Mayank verified their affiliation via an institutional email.

Learn more

Verified

Mayank verified their affiliation via an institutional email.

Learn more

• PhD
• Senior Researcher at Texas Children's Hospital

Background Clinical studies in COVID‐19 patients have demonstrated evidence of neuroinflammation in patients infected with SARS‐CoV‐2. In this pre‐clinical work, we investigate neuroinflammation in vivo in a mouse model of Alzheimer’s disease (AD) that exhibits both amyloid and tau pathology, the 3xTg‐AD mice crossed with K18 hAce2 and infected wit...

Familial Alzheimer's disease (AD) involving known AD causing genes accounts for a small fraction of cases, the vast majority are sporadic. Neuroinflammation, secondary to viral infection, has been suggested as an initiating or accelerating factor. In this work we tested the hypothesis that SARS-CoV-2 (SCV2) viral infection accelerates the developme...

Background Women exhibit higher prevalence of Alzheimer’s disease (AD) with faster cognitive decline compared to men, but the mechanisms of this dimorphism remain understudied. Astrocyte function and morphology is distinct in some regions of male and female adult brains which may reflect different courses taken by the neurodegenerative process. Add...

Background Neuroinflammation plays an important role in Alzheimer’s disease (AD) pathogenesis and disease progression leading to cognitive decline. Current efforts for non‐invasive imaging of neuroinflammation are based on using PET radiotracers. An MRI‐based contrast agent for imaging of neuroinflammation would be highly desirable due to widesprea...

Background Amyloid plaques are a pathological hallmark of Alzheimer’s disease (AD). In a recent pre‐clinical study, we showed an amyloid‐targeted liposomal macrocyclic gadolinium (Gd) contrast agent, ADx‐001, for in vivo MRI‐based detection of amyloid plaques in mouse. Although ADx‐001 showed high sensitivity at a high dose (0.2 mmol Gd/kg), the pe...

We previously reported Cell surface vimentin (CSV) as a surrogate marker for cells in a hyperphosphorylative state, leading to pathological tau deposits in mouse models. Here were investigate the correlation between a Magnetic Resonance Imaging (MRI) marker of CSV and changes in the plasma pTau biomarkers at early stages of tau pathology. We studie...

Introduction Prior preclinical studies established the utility of liposomal nanoparticle blood-pool contrast agents in visualizing the retroplacental clear space (RPCS), a marker of normal placentation, while sparing fetuses from exposure because the agent does not cross the placental barrier. In this work, we characterized RPCS disruption in a mou...

The abnormal phosphorylation of tau is a necessary precursor to the formation of tau fibrils, a marker of Alzheimer's disease. We hypothesize that hyperphosphorylative conditions may result in unique cell surface markers. We identify and demonstrate the utility of such surrogate markers to identify the hyperphosphorylative state. Methods: Cell SELE...

Introduction Prior preclinical studies established the utility of liposomal nanoparticle blood-pool contrast agents in visualizing the retroplacental clear space (RPCS), a marker of normal placentation, while sparing fetuses from exposure because the agent does not cross the placental barrier. In this work we characterized RPCS disruption in a mous...

Objective: Tumor-associated macrophages (TAMs) within the tumor immune microenvironment (TiME) of solid tumors play an important role in treatment resistance and disease recurrence. The purpose of this study was to investigate if nanoradiomics (radiomic analysis of nanoparticle contrast-enhanced images) can differentiate tumors based on TAM burden...

While a definitive Alzheimer’s disease (AD) diagnosis remains a post-mortem exercise, the ATN Research Framework proposed by the National Institute on Aging and the Alzheimer’s Association utilizes a score representing the presence of amyloid deposits (A), tau deposits (T) and neuronal degeneration markers (N), with A+T+ necessary for a positive di...

Background Chronic neuroinflammation plays a critical role in the pathophysiology of Alzheimer’s disease (AD) and related dementias. The CNS is immune privileged with restricted peripheral leukocyte traffic under normal physiological conditions. Neuroinflammation in disease brains is often accompanied by BBB compromise and increase CNS infiltration...

Background Hyperphosphorylated tau (pTau) is a characteristic of AD, leading to intracellular “tau tangles” followed by dementia. However, intracellular tau is difficult to measure in vivo, requiring a probe to enter the cell. Proteomic changes on the diseased cell‐surface however, provide a diagnostic target that eliminates the need for a probe to...

Background Hyperphosphorylated tau (pTau) is a precursor to tau tangle formation in Alzheimer's disease (AD). We have identified aptamers that bind to specific cell membrane receptors of human neuronal cells that are hyperphosphorylating tau. In this work, we built a novel targeted nanoparticle magnetic resonance imaging (MRI) contrast agent, TauX,...

Background Early detection of amyloid plaque deposits is crucial for identifying pre‐symptomatic Alzheimer’s disease (AD) patients. An amyloid imaging magnetic resonance imaging (MRI) contrast agent would have substantial utility in the clinic due to its ease of distribution and the standard use of MRI in AD patient workup. In this work, we describ...

In these preclinical studies, we describe ADx-001, an Aβ-targeted liposomal macrocyclic gadolinium (Gd) imaging agent, for MRI of amyloid plaques. The targeting moiety is a novel lipid-PEG conjugated styryl-pyrimidine. An MRI-based contrast agent such as ADx-001 is attractive because of the lack of radioactivity, ease of distribution, long shelf li...

Non-invasive methods for estimating placental fractional blood volume (FBV) are of great interest for characterization of vascular perfusion in placentae during pregnancy to identify placental insufficiency that may be indicative of local ischemia or fetal growth restriction (FGR). Nanoparticle contrast-enhanced magnetic resonance imaging (CE-MRI)...

Advances in computed tomography (CT) hardware have propelled the development of novel CT contrast agents. In particular, the spectral capabilities of x-ray CT can facilitate simultaneous imaging of multiple contrast agents. This approach is particularly useful for functional imaging of solid tumors by simultaneous visualization of multiple targets...

Introduction: Visualization of the retroplacental clear space (RPCS) may provide critical insight into the development of abnormally invasive placenta (AIP). In this pre-clinical study, we characterized the appearance of the RPCS on magnetic resonance imaging (MRI) during the second half of gestation using a liposomal gadolinium contrast agent (li...

Patients with advanced head and neck squamous cell carcinoma receiving chemotherapy have a poor prognosis partly due to normal tissue toxicity; therefore, development of a tumor-targeted drug delivery platform to minimize collateral toxicity is a goal of cancer nanomedicine. Aptamers can achieve this purpose. While conventional Systematic Evolution...

Introduction: Delivery of a nanoparticle payload to a specific cellular compartment is a prized goal of cancer nanomedicine. The well-known SELEX (systematic evolution of ligands by exponential enrichment) process is often used to identify aptamers that localize to target cellular compartments, but such aptamers cannot be guaranteed to traffic an a...

Extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles constitute the major neuropathological hallmarks of Alzheimer's disease (AD). It is now apparent that parenchymal Aβ plaque deposition precedes behavioral signs of disease by several years. The development of agents that can target these plaques may be useful as diagnost...

1H NMR and 13C NMR spectra of all new compounds; 1H NMR and MALDI mass analysis of conjugate; TEM image of liposomes and liposome stability test data. (PDF)

Boronic acids, known to bind diols, were screened to identify non-inflammatory cross-linkers for the preparation of glucose sensitive and insulin releasing agglomerates of liposomes (Agglomerated Vesicle Technology-AVT). This was done in order to select a suitable replacement for the previously used cross-linker, ConcanavalinA (ConA), a lectin know...

4-aminocarbonylphenylboronic acid tethered to DSPE-PEG-COOH. (TIF)

General scheme for the preparation of PEGylated lipid-boronic acid conjugates. (DOC)

General scheme for the preparation of PEGylated lipid-sugar conjugates. (DOC)

4-aminocarbonylphenylboronic acid tethered to Boc-n-propylamine linker. (TIF)

4-aminocarbonylphenylboronic acid tethered to n-propylamine linker. (TIF)

Loss of ark suppresses apoptosis in Uba1 clones. Uba1 ark mosaic eye-antennal disc labeled for cleaved CASPASE-3 (CAS3*) antibody (red). These discs were incubated at 30°C 12 hours before dissection (see Material and Methods). Absence of GFP marks the location of Uba1 ark clones (see arrows). There is scattered apoptosis detectable. However, this o...

UAS-diap1 rescues GMR-hid and apoptosis induced in vps25 mutants. Because the UAS-diap1 transgene failed to suppress apoptosis in Uba1 clones (Figure 1C), we tested its ability to inhibit the strong apoptotic phenotype in two other paradigms. (A) Overexpression of the IAP-antagonist hid specifically in the fly eye under GMR promoter control gives r...

“Undead” diap122-8s cells accumulate DRONC protein autonomously. (A, A′) Using MARCM, p35-expressing, ‘undead’ diap122-8s mutant clones (green) were induced in eye discs and labeled for DRONC protein (red). DRONC protein autonomously accumulates in P35-expressing diap122-8s clones (arrows). Similar results were obtained in wing discs (data not show...

Specificity of the anti-DRONC antibody. The specificity of the anti-DRONC antibody used for immunofluorescence in Figure 3, Figure 4, and Figure 5 was verified in droncI29 mosaic eye (A) and wing (B) imaginal discs. The droncI29 allele contains a premature STOP codon at position 53 [11]. droncI29 clones were induced using the MARCM system, hence th...

Ubiquitylation targets proteins for proteasome-mediated degradation and plays important roles in many biological processes including apoptosis. However, non-proteolytic functions of ubiquitylation are also known. In Drosophila, the inhibitor of apoptosis protein 1 (DIAP1) is known to ubiquitylate the initiator caspase DRONC in vitro. Because DRONC...

Ubiquitylation targets proteins for proteasome-mediated degradation and plays important roles in many biological processes including apoptosis. However, non-proteolytic functions of ubiquitylation are also known. In Drosophila, the inhibitor of apoptosis protein 1 (DIAP1) is known to ubiquitylate the initiator caspase DRONC in vitro. Because DRONC...

In mammals and Drosophila, apoptotic caspases are under positive control of the CED-4-like proteins Apaf-1 and ARK, respectively. In an EMS-mutagenesis screen, we isolated 33 ark mutants as recessive suppressors of hid-induced apoptosis. The ark mutants are loss-of-function alleles characterized by reduced developmental apoptosis. Using the phenoty...

The role of cytochrome c (Cyt c) in caspase activation has largely been established from mammalian cell-culture studies, but much remains to be learned about its physiological relevance in situ. The role of Cyt c in invertebrates has been subject to considerable controversy. The Drosophila genome contains distinct cyt c genes: cyt c-p and cyt c-d....

Cytochrome C has two apparently separable cellular functions: respiration and caspase activation during apoptosis. While a role of the mitochondria and cytochrome C in the assembly of the apoptosome and caspase activation has been established for mammalian cells, the existence of a comparable function for cytochrome C in invertebrates remains contr...

Inhibitor of apoptosis proteins (IAPs) are a conserved class of proteins that control apoptosis in both vertebrates and invertebrates. They exert their anti-apoptotic function through inhibition of caspases, the principal executioners of apoptotic cell death. Recent advances in vertebrates and Drosophila have demonstrated that IAPs use ubiquitin co...

The xanthine oxidoreductase (XOD) system, which consists of xanthine dehydrogenase (XDH) and xanthine oxidase (XO), is one of the major sources of free radicals in biological systems. The XOD system is present predominantly in the normal tissues as XDH. In damaged tissues, XDH is converted into XO, the form that generates free radicals. Therefore,...

Photodynamic therapy (PDT), a promising treatment modality, is an oxidative stress that induces apoptosis in many cancer cells in vitro and tumors in vivo. Understanding the mechanism(s) involved in PDT-mediated apoptosis may improve its therapeutic efficacy. Although studies suggest the involvement of multiple pathways, the triggering event(s) res...

Epidemiologic studies suggest that populations that consume large amounts of dietary fat are at greater risk for prostate carcinoma. Arachidonic acid and its precursor, linoleic acid, are major ingredients of animal fats and many vegetable oils that are used in the regions where prostate carcinoma is prevalent. The metabolism of arachidonic acid by...

Epidemiologic studies suggest that populations that consume large amounts of dietary fat are at greater risk for prostate carcinoma. Arachidonic acid and its precursor, linoleic acid, are major ingredients of animal fats and many vegetable oils that are used in the regions where prostate carcinoma is prevalent. The metabolism of arachidonic acid by...

The widely distributed xanthine oxidoreductase (XOR) system has been shown to be modulated upon exposure of animals to ionizing radiation through the conversion of xanthine dehydrogenase (XDH) into xanthine oxidase (XO). In the present work, radiomodification of the XOR system by phenylmethylsulfonyl fluoride (PMSF) and dithiothreitol (DTT) was exa...

Aberrant or increased expression of cyclooxygenase (COX)-2 has been implicated in the pathogenesis of many diseases including carcinogenesis. COX-2 has been shown to be over-expressed in some human cancers. Employing semi-quantitative reverse transcription-PCR, immunoblotting, and immunohistochemistry we assessed COX-2 expression in samples of pair...

The xanthine oxidoreductase system is one of the major sources of free radicals in many pathophysiological conditions. Since ionizing radiations cause cell damage and death, the xanthine oxidoreductase system may contribute to the detrimental effects in irradiated systems. Therefore, modulation of the xanthine oxidoreductase system by radiation has...

Cellular membranes are vital elements, and their integrity is extremely essential for the viability of the cells. We studied the effects of high linear energy transfer (LET) radiation on the membranes. Rabbit erythrocytes (1 x 10(7) cells/ml) and microsomes (0.6 mg protein/ml) prepared from liver of rats were irradiated with 7Li ions of energy 6.42...

Microsomes prepared from liver of male Sprague Dawley rats were irradiated with various fluences of 45 MeV Li-7 and 68 MeV O-16 charged particles. The change in fluidity and lipid peroxidation was measured in terms of fluorescence polarization and MDA formation respectively. The fluidity of membrane was found to decrease with increase in fluence of...