Ashutosh Chilkoti
Duke University
MicelleFusion proteinBiophysicsDrug carrierNanoparticleNanotechnologyChemistryPolymer chemistryLower critical solution temperatureMaterials scienceConjugateStreptavidinPeptideDrug deliveryElastinRecombinant DNAPolymerBiochemistryMedicinePharmacology
398Publications
103H-index
26.6kCitations
Publications 390
Newest
#1Irene C. Jenkins (Duke University)
#2Joshua J. Milligan (Duke University)
Last. Ashutosh Chilkoti (Duke University)H-Index: 103
view all 3 authors...
Elastin-like polypeptides (ELPs) are thermally responsive biopolymers that consist of a repeated amino acid motif derived from human tropoelastin. These peptides exhibit temperature-dependent phase behavior that can be harnessed to produce stimuli-responsive biomaterials, such as nanoparticles or injectable drug delivery depots. As ELPs are genetically encoded, the properties of ELP-based biomaterials can be controlled with a precision that is unattainable with synthetic polymers. Unique ELP arc...
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#1Kelly M. Hainline (Duke University)H-Index: 3
#2Lucas S. Shores (Duke University)H-Index: 2
Last. Joel H. Collier (Duke University)H-Index: 36
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Complement protein C3dg, a key linkage between innate and adaptive immunity, is capable of stimulating both humoral and cell-mediated immune responses, leading to considerable interest in its use as a molecular adjuvant. However, the potential of C3dg as an adjuvant is limited without ways of controllably assembling multiple copies of it into vaccine platforms. Here, we report a strategy to assemble C3dg into supramolecular nanofibers with excellent compositional control, using β-tail fusion tag...
1 CitationsSource
#1Cassio M. Fontes (Duke University)H-Index: 5
#2Barbara D. Lipes (Duke University)H-Index: 6
Last. Ashutosh Chilkoti (Duke University)H-Index: 103
view all 19 authors...
Ebola virus (EBOV) hemorrhagic fever outbreaks have been challenging to deter due to the lack of health care infrastructure in disease-endemic countries and a corresponding inability to diagnose and contain the disease at an early stage. EBOV vaccines and therapies have improved disease outcomes, but the advent of an affordable, easily accessed, mass-produced rapid diagnostic test (RDT) that matches the performance of more resource-intensive polymerase chain reaction (PCR) assays would be invalu...
1 CitationsSource
#1Xiangze Zeng (WashU: Washington University in St. Louis)H-Index: 7
#2Chengwen Liu (University of Texas at Austin)H-Index: 12
Last. Rohit V. Pappu (WashU: Washington University in St. Louis)H-Index: 61
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Many naturally occurring elastomers are intrinsically disordered proteins (IDPs) built up of repeating units, and they can demonstrate two types of thermoresponsive phase behavior. Systems characterized by lower critical solution temperatures (LCSTs) undergo phase separation above the LCST, whereas systems characterized by upper critical solution temperatures (UCSTs) undergo phase separation below the UCST. There is congruence between thermoresponsive coil–globule transitions and phase behavior,...
3 CitationsSource
#1Katharina Laaß (MLU: Martin Luther University of Halle-Wittenberg)
#2Felipe García Quiroz (Duke University)H-Index: 14
Last. Dariush Hinderberger (MLU: Martin Luther University of Halle-Wittenberg)H-Index: 27
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Many intrinsically disordered proteins (IDPs) in nature may undergo liquid-liquid phase separation to assemble membraneless organelles with varied liquid-like properties and stability/dynamics. While solubility changes underlie these properties, little is known about hydration dynamics in phase-separating IDPs. Here, by studying IDP polymers of similar composition but distinct liquid-like dynamics and stability upon separation, namely, thermal hysteresis, we probe at a nanoscopic level hydration...
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#1Jacob T. Heggestad (Duke University)H-Index: 5
#1Jacob T. Heggestad (Duke University)H-Index: 2
Last. Ashutosh Chilkoti (Duke University)H-Index: 103
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Highly sensitive, specific, and point-of-care (POC) serological assays are an essential tool to manage the COVID-19 pandemic. Here, we report on a microfluidic, multiplexed POC test that can profile the antibody response against multiple SARS-CoV-2 antigens - Spike S1 (S1), Nucleocapsid (N), and the receptor binding domain (RBD) - simultaneously from a 60 microliter drop of blood, plasma, or serum. We assessed the levels of anti-SARS-CoV-2 antibodies in plasma samples from 19 individuals (at mul...
1 CitationsSource
#1Caslin A. Gilroy (University of California, Berkeley)H-Index: 3
#2Megan E. Capozzi (Duke University)H-Index: 15
Last. Ashutosh Chilkoti (Duke University)H-Index: 103
view all 7 authors...
There is great interest in identifying a glucagon-like peptide-1 (GLP-1)–based combination therapy that will more effectively promote weight loss in patients with type 2 diabetes. Fibroblast growth factor 21 (FGF21) is a compelling yet previously unexplored drug candidate to combine with GLP-1 due to its thermogenic and insulin-sensitizing effects. Here, we describe the development of a biologic that fuses GLP-1 to FGF21 with an elastin-like polypeptide linker that acts as a sustained release mo...
4 CitationsSource
#1Michael Dzuricky (Duke University)H-Index: 12
#2Bradley A. Rogers (PSU: Pennsylvania State University)H-Index: 4
Last. Ashutosh Chilkoti (Duke University)H-Index: 103
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Phase separation of intrinsically disordered proteins (IDPs) is a remarkable feature of living cells to dynamically control intracellular partitioning. Despite the numerous new IDPs that have been identified, progress towards rational engineering in cells has been limited. To address this limitation, we systematically scanned the sequence space of native IDPs and designed artificial IDPs (A-IDPs) with different molecular weights and aromatic content, which exhibit variable condensate saturation ...
24 CitationsSource
#1Rebecca D. Dodd (UI: University of Iowa)H-Index: 14
#2Amanda Scherer (UI: University of Iowa)H-Index: 6
Last. David G. Kirsch (Duke University)H-Index: 62
view all 19 authors...
Purpose: Nanoparticle-encapsulated drug formulations can improve responses to conventional chemotherapy by increasing drug retention within the tumor and by promoting a more effective anti-tumor immune response than free drug. New drug delivery modalities are needed in sarcomas because they are often chemo-resistant cancers, but the rarity of sarcomas and the complexity of diverse subtypes makes it challenging to investigate novel drug formulations. Experimental Design: New drug formulations can...
1 CitationsSource
#1Xiangze Zeng (WashU: Washington University in St. Louis)H-Index: 7
#2Alex S. Holehouse (WashU: Washington University in St. Louis)H-Index: 26
Last. Rohit V. Pappu (WashU: Washington University in St. Louis)H-Index: 61
view all 5 authors...
Abstract Phase separation is thought to underlie spatial and temporal organization that is required for controlling biochemical reactions in cells. Multivalence of interaction motifs also known as stickers is a defining feature of proteins that drive phase separation. Intrinsically disordered proteins with stickers uniformly distributed along the linear sequence can serve as scaffold molecules that drive phase separation. The sequence-intrinsic contributions of disordered proteins to phase separ...
18 CitationsSource