Nicholas A. Smith

ORCID: 0000-0001-8894-4249
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About
Contact & Profiles
Research Areas
  • Viral-associated cancers and disorders
  • Neuropeptides and Animal Physiology
  • Cytomegalovirus and herpesvirus research
  • Nicotinic Acetylcholine Receptors Study
  • Cell death mechanisms and regulation
  • Receptor Mechanisms and Signaling
  • Lymphoma Diagnosis and Treatment
  • Parvovirus B19 Infection Studies
  • Pancreatic function and diabetes
  • Herpesvirus Infections and Treatments
  • Ubiquitin and proteasome pathways
  • RNA Interference and Gene Delivery
  • Photodynamic Therapy Research Studies
  • Erythrocyte Function and Pathophysiology
  • Surface Chemistry and Catalysis
  • Enzyme Structure and Function
  • Hemoglobin structure and function
  • Toxoplasma gondii Research Studies
  • Graphene research and applications
  • Metabolism, Diabetes, and Cancer
  • Autophagy in Disease and Therapy
  • Lipid Membrane Structure and Behavior
  • Endoplasmic Reticulum Stress and Disease
  • Insect symbiosis and bacterial influences
  • Greenhouse Technology and Climate Control

La Trobe University
2016-2024

SUNY Upstate Medical University
2014-2021

University of Southern Mississippi
2021

University of Colorado Denver
2017-2020

Brigham and Women's Hospital
2019

University of Colorado Anschutz Medical Campus
2018

Florey Institute of Neuroscience and Mental Health
2017

The University of Melbourne
2017

University of Vermont
2016

Vanderbilt University
2014

Epstein-Barr virus (EBV) causes Burkitt, Hodgkin, and post-transplant B cell lymphomas. How EBV remodels metabolic pathways to support rapid outgrowth remains largely unknown. To gain insights, primary human cells were profiled by tandem-mass-tag-based proteomics at rest nine time points after infection; >8,000 host 29 viral proteins quantified, revealing mitochondrial remodeling induction of one-carbon (1C) metabolism. EBV-encoded EBNA2 its target MYC required for upregulation the central...

10.1016/j.cmet.2019.06.003 article EN cc-by Cell Metabolism 2019-06-27

ABSTRACT Epstein-Barr virus (EBV) is a well-established B-cell-tropic associated with various lymphoproliferative diseases of both B-cell and non-B-cell origin. EBV number T-cell lymphomas; however, in vitro studies utilizing prototypical type 1 (EBV-1) laboratory strains have generally failed to readily infect mature T cells culture. The difficulties performing experiments left questions regarding the role pathogenesis EBV-positive largely unresolved. We report here that 2 (EBV-2) strain...

10.1128/jvi.03001-14 article EN Journal of Virology 2014-12-11

Quite comparable: A graphene monolayer is used as a substrate for the growth of two-dimensional hydrogen-bonded supramolecular structures (see STM image). The formation these extended arises from commensurability between their dimensions and moiré pattern formed by graphene. Detailed facts importance to specialist readers are published "Supporting Information". Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted authors. Please note: publisher...

10.1002/anie.200905503 article EN Angewandte Chemie International Edition 2010-02-04

The fish-hunting marine cone snail Conus geographus uses a specialized venom insulin to induce hypoglycemic shock in its prey. We recently showed that this insulin, Con-Ins G1, has unique characteristics relevant the design of new therapeutics. Here, we show snails provide rich source minimized ligands vertebrate receptor. Insulins from C. , tulipa and kinoshitai exhibit diverse sequences, yet all bind activate human Molecular dynamics reveal modes action are distinct any other insulins...

10.7554/elife.41574 article EN cc-by eLife 2019-02-12

BAK and BAX execute intrinsic apoptosis by permeabilising the mitochondrial outer membrane. Their activity is regulated through interactions with pro-survival BCL-2 family proteins non-BCL-2 including channel protein VDAC2. VDAC2 important for bringing both to mitochondria where they their apoptotic function. Despite this function in apoptosis, while members are well characterised have culminated development of drugs that target these interfaces induce cancer cell interaction between remains...

10.1371/journal.pbio.3002617 article EN cc-by PLoS Biology 2024-05-02

Abstract During apoptosis, Bak and Bax are activated by BH3-only proteins binding to the α2–α5 hydrophobic groove; is also via a rear pocket. Here we report that antibodies can directly activate mitochondrial α1–α2 loop. A monoclonal antibody (clone 7D10) binds close α1 in non-activated induce conformational change, oligomerization, cytochrome c release. Anti-FLAG containing FLAG epitope α1. An 3C10) loop activates Bax, but blocks translocation of cytosolic Bax. Tethers within show 7D10...

10.1038/ncomms11734 article EN cc-by Nature Communications 2016-05-24

Epstein-Barr virus (EBV) is associated with a number of T-cell diseases, including some peripheral lymphomas, hemophagocytic lymphohistiocytosis, and chronic active EBV disease. The tropism for B cells epithelial cell infection has been well characterized, but T minimally explored. We have recently shown that the type 2 (EBV-2) strain unique ability to infect mature cells. Utilizing an ex vivo model, we sought understand viral glycoprotein cellular receptor required EBV-2 Here, using...

10.1128/jvi.00428-20 article EN Journal of Virology 2020-03-30

The 2 strains of Epstein-Barr virus (EBV), EBV type 1 (EBV-1) and EBV-2, differ in latency genes, suggesting that they use distinct mechanisms to establish latency. We previously reported EBV-2 infects T cells vitro. In this study, we tested the possibility vivo. Purified T-cell fractions isolated from children positive for EBV-1 or their mothers were examined presence type. detected all samples obtained EBV-2–infected at 12 months age, with some retaining EBV-2–positive through 24 persists...

10.1093/infdis/jix363 article EN The Journal of Infectious Diseases 2017-07-25

Epstein-Barr virus (EBV) has been classified into two strains, EBV type 1 (EBV-1) and 2 (EBV-2) based on genetic variances differences in transforming capacity. EBV-1 readily transforms B cells culture while EBV-2 is poorly transforming. The differing abilities to immortalize vitro suggest that vivo these viruses likely use alternative approaches establish latency. Indeed, we recently reported a unique cell tropism for T cells, infecting healthy Kenyan infants, strongly suggesting infection...

10.1128/jvi.00813-18 article EN Journal of Virology 2018-08-09

Etoposide is a topoisomerase II poison that utilized to treat broad spectrum of human cancers. Despite its wide clinical use, 2-3% patients treated with etoposide eventually develop treatment-related acute myeloid leukemias (t-AMLs) characterized by rearrangements the MLL gene. The molecular basis underlying development these t-AMLs not well understood; however, previous studies have implicated metabolites (i.e., quinone) and IIβ in leukemogenic process. Although interactions between quinone...

10.1021/bi500421q article EN publisher-specific-oa Biochemistry 2014-04-28

The Epstein-Barr virus (EBV) viral glycoprotein gp350 has been proposed as a candidate antigen for an EBV vaccine. However, the formulations of these vaccines have not taken into account presence 2 unique strains (EBV-1 and EBV-2) present in areas high incidence EBV-associated cancer, Burkitt lymphoma.In this study, we analyze kinetics EBV-1 EBV-2 infection asymptomatic infant cohort from Kisumu, Kenya. We also analyzed antibody response against 5 antigens, (IgG IgA), VCA (IgG), EBNA-1 EAd...

10.1093/infdis/jiy601 article EN The Journal of Infectious Diseases 2018-10-09

BECN1/Beclin 1 is a critical protein in the initiation of autophagosome formation. Recent studies have shown that phosphorylation BECN1 by STK4/MST1 at threonine 108 (T108) within its BH3 domain blocks macroautophagy/autophagy increasing affinity for negative regulators, anti-apoptotic proteins BCL2/Bcl-2 and BCL2L1/Bcl-xL. It was proposed this increased binding due to formation an electrostatic interaction with conserved histidine residue on molecules. Here, we performed biophysical which...

10.1080/15548627.2018.1564557 article EN Autophagy 2019-01-04

Background. We previously reported that infants in Kenya were infected with Epstein-Barr virus (EBV) at <6 months of age, suggesting mothers the likely source transmissible to infant. In this study, we investigated whether breast milk contained infectious EBV and role malaria shedding milk.

10.1093/infdis/jiv290 article EN The Journal of Infectious Diseases 2015-05-17

Varicella-zoster virus and human cytomegalovirus infect a majority of the global population. While they often cause mild disease, serious illness complications can arise. Unfortunately, there are few effective drugs to treat these viruses, many toxic. To complicate this, viruses restricted replication in cells tissues, making them difficult study traditional animal models. Current models rely heavily on fetal be prohibitively expensive, complicated generate. tissue provide helpful insights,...

10.1128/jvi.01082-20 article EN Journal of Virology 2020-09-02

Abstract Background and Objective Aminolevulinic acid photodynamic therapy (ALA‐PDT) depends on drug metabolism into porphyrins. Clinically, ALA‐PDT has been used with a wide range of protocols for treating both epidermal dermal targets, despite limited understanding porphyrin biodistribution over time. We studied accumulation after topical application ALA in vivo, also describe the porcine ear as new animal model to study adnexal glands. Study Design/Materials Methods The microanatomy...

10.1002/lsm.20734 article EN Lasers in Surgery and Medicine 2009-02-01

Epstein-Barr virus (EBV) is associated with Burkitt's lymphoma (BL), and in regions of sub-Saharan Africa where endemic BL common, both the EBV Type 1 (EBV-1) 2 strains (EBV-2) are found. Little known about genetic variation areas Africa. In present study, spontaneous lymphoblastoid cell lines (LCLs) were generated from samples obtained Kenya. Polymerase chain reaction (PCR) amplification genome was done using multiple primers sequenced by next-generation sequencing (NGS). Phylogenetic...

10.1371/journal.pone.0125420 article EN cc-by PLoS ONE 2015-05-01

Abstract Relaxin family peptide receptor 2 (RXFP2) is a GPCR known for its role in reproductive function. It structurally related to the human relaxin RXFP1 and can be activated by gene-2 (H2) as well cognate ligand insulin-like 3 (INSL3). Both receptors possess an N-terminal low-density lipoprotein type (LDLa) module that necessary activation joined leucine-rich repeat domain linker. This linker has been shown important H2 binding of herein we investigate equivalent region RXFP2. We...

10.1038/s41598-017-03638-4 article EN cc-by Scientific Reports 2017-06-06

Domain-minimized insulin receptors (IRs) have enabled crystallographic analysis of insulin-bound "micro-receptors." In such structures, the C-terminal segment B chain inserts between conserved IR domains, unmasking an invariant receptor-binding surface that spans both A and chains. This "open" conformation not only rationalizes inactivity single-chain (SCI) analogs (in which chains are directly linked), but also suggests connecting (C) domains sufficient length will bind IR. Here, we report...

10.1074/jbc.m117.808667 article EN cc-by Journal of Biological Chemistry 2017-11-07
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