Joseph E. Darling

ORCID: 0000-0001-7353-6904
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About
Contact & Profiles
Research Areas
  • Regulation of Appetite and Obesity
  • Biochemical Analysis and Sensing Techniques
  • Pancreatic function and diabetes
  • Malaria Research and Control
  • Enzyme Structure and Function
  • Adipose Tissue and Metabolism
  • Redox biology and oxidative stress
  • Protein Structure and Dynamics
  • Neurofibromatosis and Schwannoma Cases
  • Biochemical and Molecular Research
  • Ubiquitin and proteasome pathways
  • Neuroblastoma Research and Treatments
  • Lipid Membrane Structure and Behavior
  • Photosynthetic Processes and Mechanisms
  • Genomics, phytochemicals, and oxidative stress
  • Food Industry and Aquatic Biology
  • Endoplasmic Reticulum Stress and Disease
  • Advanced Electron Microscopy Techniques and Applications
  • Hepatitis B Virus Studies
  • Cytomegalovirus and herpesvirus research
  • Diet, Metabolism, and Disease
  • Polyomavirus and related diseases
  • Sarcoma Diagnosis and Treatment
  • Mass Spectrometry Techniques and Applications
  • Complement system in diseases

Frederick National Laboratory for Cancer Research
2020-2023

National Cancer Institute
2020-2021

National Institutes of Health
2020-2021

Center for Cancer Research
2020-2021

Leidos (United States)
2020

Leidos Biomedical Research Inc. (United States)
2020

Cancer Institute (WIA)
2020

Syracuse University
2013-2016

University of North Carolina at Chapel Hill
2011

Malaria parasites use the RhopH complex for erythrocyte invasion and channel-mediated nutrient uptake. As member proteins are unique to Plasmodium spp., how they interact traffic through subcellular sites serve these essential functions is unknown. We show that synthesized as a soluble of CLAG3, RhopH2, RhopH3 with 1:1:1 stoichiometry. After transfer new host cell, crosses vacuolar membrane surrounding intracellular parasite becomes integral PTEX translocon-dependent process. present 2.9 Å...

10.7554/elife.65282 article EN public-domain eLife 2021-01-04

The majority of pathogenic mutations in the neurofibromatosis type I (NF1) gene reduce total neurofibromin protein expression through premature truncation or microdeletion, but it is less well understood how loss-of-function missense variants drive NF1 disease. We have found that patient codons 844 to 848, which correlate with a severe phenotype, cause instability and exert an additional dominant-negative action whereby wild-type also becomes destabilized dimerization. used our cryogenic...

10.1073/pnas.2208960120 article EN cc-by-nc-nd Proceedings of the National Academy of Sciences 2023-01-23

Ghrelin O-acyltransferase (GOAT) is an integral membrane acyltransferase responsible for catalyzing a serine-octanoylation posttranslational modification within the peptide hormone ghrelin. requires this octanoylation its biological activity in stimulating appetite and regulating other physiological pathways involved energy balance. Blocking ghrelin acylation using GOAT inhibitors new potential avenue to treat health conditions impacted by signaling, such as obesity diabetes. Designing novel...

10.1021/bi5010359 article EN Biochemistry 2015-01-06

We report the determination of structure Escherichia coli β-galactosidase at a resolution ∼1.8 Å using data collected on 200 kV CRYO ARM microscope equipped with K3 direct electron detector. The were in single 24 h session by recording images from an array 7 × holes each stage position automated collection program SerialEM . In addition to expected features such as densities aromatic residues, map also shows density bumps corresponding locations hydrogen atoms. are useful assigning absolute...

10.1107/s2052252520006855 article EN cc-by IUCrJ 2020-06-10

Ghrelin is a peptide hormone involved in multiple physiological processes related to energy homeostasis. This features unique posttranslational serine octanoylation modification catalyzed by the enzyme ghrelin O-acyltransferase, with essential for bind and activate its cognate receptor. deacylation rapidly occurs circulation, both desacyl playing important roles biological signaling. Understanding regulation impact of signaling requires ability protect from samples such as blood serum or...

10.1210/en.2016-1657 article EN Endocrinology 2016-09-13

Ghrelin is a 28 amino acid hormonal peptide that intimately related to the regulation of food intake and body weight. Once secreted, ghrelin binds growth hormone secretagogue receptor-1a, only known receptor for capable activating number signaling cascades, ultimately resulting in an increase adiposity. Because has been linked overeating development obesity, pharmacological interventions have generated order interfere with either activation or interrupting as means reducing appetite decrease...

10.3389/fendo.2015.00144 article EN cc-by Frontiers in Endocrinology 2015-09-25

Malaria is a devastating disease caused by protozoan parasite. It affects over 300 million individuals and results in 400 000 deaths annually, most of whom are young children under the age five. Hexokinase, first enzyme glucose metabolism, plays an important role infection process represents promising target for therapeutic intervention. Here, cryo-EM structures two conformational states Plasmodium vivax hexokinase (PvHK) reported at resolutions ∼3 Å. shown that unlike other known...

10.1107/s2052252520002456 article EN cc-by IUCrJ 2020-03-25
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