Muniasamy Neerathilingam

Institute of Bioinformatics

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David E. Volk

Robert Bosch (Germany)

Bruce A. Luxon

Georgetown University

Todd M. Alam

Sandia National Laboratories

Mary Kathleen Alam

Sandia National Laboratories

Chetan Chandola

Institute of Bioinformatics

G.A.S. Ansari

The University of Texas Medical Branch at Galveston

Sumukh Mysore

Noble Research Institute

Sneha Bairy

National Centre for Biological Sciences

Swapna Sarkar

The University of Texas Medical Branch at Galveston

Lakshmi Narayanan Gopalan

Central Food Technological Research Institute

Cooperative Institutions

Institute of Bioinformatics

The University of Texas Medical Branch at Galveston

Manipal Academy of Higher Education

The University of Texas Health Science Center at Houston

National Centre for Biological Sciences

Institute for Stem Cell Biology and Regenerative Medicine

The University of Texas MD Anderson Cancer Center

Tata Institute of Fundamental Research

Institute of Molecular Medicine

Central Food Technological Research Institute

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1H NMR metabonomic study of rat response to tri-phenyl phosphate and tri-butyl phosphate exposure

Metabolomics (2010)

Todd M. Alam Mary Kathleen Alam Muniasamy Neerathilingam David E. Volk Swapna Sarkar

10.1007/s11306-010-0205-z

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Citations (18)

Tracking of Nuclear Production using Indigenous Species: Final LDRD Report

Todd M. Alam Mary Kathleen Alam Sarah McIntyre David E. Volk Muniasamy Neerathilingam

Our LDRD research project sought to develop an analytical method for detection of chemicals used in nuclear materials processing. Our approach is distinctly different than current research involving hardware-based sensors. By utilizing the response of indigenous species of plants and/or animals surrounding (or within) a nuclear processing facility, we propose tracking 'suspicious molecules' relevant to nuclear materials processing. As proof of concept, we have examined TBP, tributylphosphate, used in uranium enrichment as well as plutonium extraction from spent nuclear fuels. We will compare TBP to the TPP (triphenylphosphate) analog to determine the uniqueness of the metabonomic response. We show that there is a unique metabonomic response within our animal model to TBP. The TBP signature can further be delineated from that of TPP. We have also developed unique methods of instrumental transfer for metabonomic data sets.

Tracking (education)

Nuclear material

Nuclear Fuel

10.2172/1324990

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Application of aptamers in diagnostics, drug-delivery and imaging

Journal of Biosciences (2016)

Chetan Chandola Sheetal S. Kalme Marco G. Casteleijn Arto Urtti Muniasamy Neerathilingam

Aptamer

Targeted drug delivery

10.1007/s12038-016-9632-y

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Citations (77)

Investigation of Chemometric Instrumental Transfer Methods for High-Resolution NMR

Analytical Chemistry (2009)

Todd M. Alam Mary Kathleen Alam Sarah McIntyre David E. Volk Muniasamy Neerathilingam

The implementation of direct standardization (DS), piecewise direct standardization (PDS), and double-window piecewise direct standardization (DWPDS) instrumental transfer techniques for high-resolution 1H NMR spectral data was explored. The ability to transfer a multivariate calibration model developed for a "master or target" NMR instrument configuration to seven different ("secondary") NMR instrument configurations was measured. Partial least-squares (PLS) calibration of glucose, glycine, and citrate metabolite relative concentrations in model mixtures following mapping of the secondary instrumental configurations using DS, PDS, or DWPDS instrumental transfer allowed the performance of the different transfer methods to be assessed. Results from these studies suggest that DS and PDS transfer techniques produce similar improvements in the error of prediction compared to each other and provide a significant improvement over standard spectral preprocessing techniques including reference deconvolution and spectral binning. The DS instrumental transfer method produced the largest percent improvement in the predictions of concentrations for these model mixtures but, in general, required that additional transfer calibration standards be used. Limitations of the different instrumental transfer methods with respect to sample subset selection are also discussed.

Chemometrics

10.1021/ac900262g

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Citations (33)

CD44 aptamer mediated cargo delivery to lysosomes of retinal pigment epithelial cells to prevent age-related macular degeneration

Biochemistry and Biophysics Reports (2019)

Chetan Chandola Marco G. Casteleijn Urvashi M. Chandola Lakshmi Narayanan Gopalan Arto Urtti

Age related macular degeneration (AMD) is a progressive, neurodegenerative disorder that leads to the severe loss of central vision in elderlies. The health of retinal pigment epithelial (RPE) cells is critical for the onset of AMD. Chronic oxidative stress along with loss of lysosomal activity is a major cause for RPE cell death during AMD. Hence, development of a molecule for targeted lysosomal delivery of therapeutic protein/drugs in RPE cells is important to prevent RPE cell death during AMD. Using human RPE cell line (ARPE-19 cells) as a study model, we confirmed that hydrogen peroxide (H2O2) induced oxidative stress results in CD44 cell surface receptor overexpression in RPE cells; hence, an important target for specific delivery to RPE cells during oxidative stress. We also demonstrate that the known nucleic acid CD44 aptamer - conjugated with a fluorescent probe (FITC) - is delivered into the lysosomes of CD44 expressing ARPE-19 cells. Hence, as a proof of concept, we demonstrate that CD44 aptamer may be used for lysosomal delivery of cargo to RPE cells under oxidative stress, similar to AMD condition. Since oxidative stress may induce wet and dry AMD, both, along with proliferative vitreoretinopathy, CD44 aptamer may be applicable as a carrier for targeted lysosomal delivery of therapeutic cargoes in ocular diseases showing oxidative stress in RPE cells.

Aptamer

10.1016/j.bbrep.2019.100642

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Citations (13)

Investigations of Chemometric Instrumental Transfer in High Resolution NMR Metabonomic Data Sets.

Todd M. Alam Mary Kathleen Alam Sarah McIntyre David E. Volk Muniasamy Neerathilingam

Chemometrics

Source

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1H Nuclear Magnetic Resonance (NMR) Metabolomic Study of Chronic Organophosphate Exposure in Rats

Metabolites (2012)

Todd M. Alam Muniasamy Neerathilingam Mary Kathleen Alam David E. Volk G.A.S. Ansari

1H NMR spectroscopy and chemometric analysis were used to characterize rat urine obtained after chronic exposure to either tributyl phosphate (TBP) or triphenyl phosphate (TPP). In this study, the daily dose exposure was 1.5 mg/kg body weight for TBP, or 2.0 mg/kg body weight for TPP, administered over a 15-week period. Orthogonal signal correction (OSC) -filtered partial least square discriminant analysis (OSC-PLSDA) was used to predict and classify exposure to these organophosphates. During the development of the model, the classification error was evaluated as a function of the number of latent variables. NMR spectral regions and corresponding metabolites important for determination of exposure type were identified using variable importance in projection (VIP) coefficients obtained from the OSC-PLSDA analysis. As expected, the model for classification of chronic (1.5–2.0 mg/kg body weight daily) TBP or TPP exposure was not as strong as the previously reported model developed for identifying acute (15–20 mg/kg body weight) exposure. The set of majorly impacted metabolites identified for chronic TBP or TPP exposure was slightly different than those metabolites previously identified for acute exposure. These metabolites were then mapped to different metabolite pathways and ranked, allowing the metabolic response to chronic organophosphate exposure to be addressed.

10.3390/metabo2030479

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Citations (14)

Targeted Delivery of Doxorubicin Through CD44 Aptamer to Cancer Cells

Therapeutic Delivery (2021)

Jagadish Natesh Chetan Chandola Syed Musthapa Meeran Muniasamy Neerathilingam

Aim: The current investigation is focused on the targeted delivery of doxorubicin through CD44 aptamer-mediated active targeting to the human breast cancer cells. Methods: CD44 aptamer-doxorubicin (Apt-Dox) conjugates were developed by incubating different molar ratios of aptamer and doxorubicin. Cytotoxicity, selective intracellular accumulation and uptake of the Apt–Dox conjugates were analyzed to evaluate the efficacy of Apt–Dox conjugates. Results: Dox was efficiently conjugated with aptamer at 1:2 Apt–Dox molar ratios. Apt–Dox conjugate significantly inhibited the proliferation of CD44-overexpressing breast cancer cells, whereas negligible inhibition of cell proliferation was found in the control cells. Apt–Dox conjugate selectively internalized and accumulated in CD44-overexpressing cells. Conclusion: Apt–Dox conjugate selectively delivers doxorubicin to CD44-expressing cancer cells, thereby inhibiting selective cell proliferation and enhancing the targeted therapy.

Aptamer

Conjugate

Targeted drug delivery

Antibody-drug conjugate

10.4155/tde-2021-0038

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Citations (15)

Super-rapid race for saving lives by developing COVID-19 vaccines

Berichte aus der medizinischen Informatik und Bioinformatik/Journal of integrative bioinformatics (2021)

Anusha Uttarilli Sridhar Amalakanti Phaneeswara-Rao Kommoju Srihari Sharma Pankaj Goyal

Abstract The pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people and claimed thousands of lives. Starting in China, it is arguably the most precipitous global health calamity of modern times. The entire world has rocked back to fight against the disease and the COVID-19 vaccine is the prime weapon. Even though the conventional vaccine development pipeline usually takes more than a decade, the escalating daily death rates due to COVID-19 infections have resulted in the development of fast-track strategies to bring in the vaccine under a year’s time. Governments, companies, and universities have networked to pool resources and have come up with a number of vaccine candidates. Also, international consortia have emerged to address the distribution of successful candidates. Herein, we summarize these unprecedented developments in vaccine science and discuss the types of COVID-19 vaccines, their developmental strategies, and their roles as well as their limitations.

Pandemic

Coronavirus

2019-20 coronavirus outbreak

10.1515/jib-2021-0002

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Citations (24)

Megaplasmid - A promising tool for higher protein production

Biochemical and Biophysical Research Communications (2018)

Muniasamy Neerathilingam Sumukh Mysore Lakshmi Narayanan Gopalan Chetan Chandola Narendrakumar Sekar

Concatemer

10.1016/j.bbrc.2018.11.096

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Citations (2)