Ashutosh Chilkoti

Overview:

Ashutosh Chilkoti is the Alan L. Kaganov Professor of Biomedical Engineering and Chair of the Department of Biomedical Engineering at Duke University.

My research in biomolecular engineering and biointerface science focuses on the development of new molecular tools and technologies that borrow from molecular biology, protein engineering, polymer chemistry and surface science that we then exploit for the development of applications that span the range from bioseparations, plasmonic biosensors, low-cost clinical diagnostics, and drug delivery.

Positions:

Alan L. Kaganov Distinguished Professor of Biomedical Engineering

Biomedical Engineering
Pratt School of Engineering

Professor of Biomedical Engineering

Biomedical Engineering
Pratt School of Engineering

Research Professor of Global Health

Duke Global Health Institute
Institutes and Provost's Academic Units

Professor in the Department of Chemistry

Chemistry
Trinity College of Arts & Sciences

Core Faculty in Innovation & Entrepreneurship

Duke Innovation & Entrepreneurship
Institutes and Provost's Academic Units

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 1991

University of Washington

Grants:

A novel sustained-release immunotoxin for treatment of glioblastoma multiforme

Administered By
Biomedical Engineering
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Plasmonically Enhanced Point-of-care Detection of Cardiac Biomarkers by a Smart Phone

Administered By
Electrical and Computer Engineering
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Genetically Encoded Smart Biohybrid Materials

Administered By
Biomedical Engineering
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

DMREF: Collaborative Research: High throughput Exploration of Sequence Space of Peptide Polymers that Exhibit Aqueous Demixing Phase Behavior

Administered By
Biomedical Engineering
Awarded By
National Science Foundation
Role
Principal Investigator
Start Date
End Date

In situ Enzymatic Synthesis of Aptamer Targeted Polynucleotide Drug Nanoparticles for Cancer Therapy

Administered By
Mechanical Engineering and Materials Science
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Publications:

Nanoscopic Dynamics Dictate the Phase Separation Behavior of Intrinsically Disordered Proteins.

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/dehydration dynamics in IDPs as they reversibly switch between phase separation states. Using continuous-wave electron paramagnetic resonance (CW EPR) spectroscopy, we observe distinct backbone and amino acid side-chain hydration dynamics in these IDPs. This nanoscopic view reveals that side-chain rehydration creates a dynamic water shield around the main-chain backbone that effectively and counterintuitively prevents water penetration and governs IDP solubility. We find that the strength of this superficial water shell is a sequence feature of IDPs that encodes for the stability of their phase-separated assemblies. Our findings expose and offer an initial understanding of how the complexity of nanoscopic water-IDP interactions dictate their rich phase separation behavior.
Authors
Laaß, K; Quiroz, FG; Hunold, J; Roberts, S; Chilkoti, A; Hinderberger, D
MLA Citation
Laaß, Katharina, et al. “Nanoscopic Dynamics Dictate the Phase Separation Behavior of Intrinsically Disordered Proteins.Biomacromolecules, vol. 22, no. 2, Feb. 2021, pp. 1015–25. Epmc, doi:10.1021/acs.biomac.0c01768.
URI
https://scholars.duke.edu/individual/pub1471436
PMID
33403854
Source
epmc
Published In
Biomacromolecules
Volume
22
Published Date
Start Page
1015
End Page
1025
DOI
10.1021/acs.biomac.0c01768

Concentration-Independent Multivalent Targeting of Cancer Cells by Genetically Encoded Core-Crosslinked Elastin/Resilin-like Polypeptide Micelles.

Valency is a fundamental principle to control macromolecular interactions and is used to target specific cell types by multivalent ligand-receptor interactions using self-assembled nanoparticle carriers. At the concentrations encountered in solid tumors upon systemic administration, these nanoparticles are, however, likely to show critical micelle concentration (CMC)-dependent disassembly and thus loss of function. To overcome this limitation, core-crosslinkable micelles of genetically encoded resilin-/elastin-like diblock polypeptides were recombinantly synthesized. The amphiphilic constructs were covalently photo-crosslinked through the genetically encoded unnatural amino acid <i>para</i>-azidophenylalanine in their hydrophobic block and they carried different anticancer ligands on their hydrophilic block: the wild-type tenth human fibronectin type III domain, a GRGDSPAS peptide-both targeting α<sub>v</sub>β<sub>3</sub> integrin-and an engineered variant of the third fibronectin type III domain of tenascin C that is a death receptor 5 agonist. Although uncrosslinked micelles lost most of their targeting ability below their CMC, the crosslinked analogues remained active at concentrations up to 1000-fold lower than the CMC, with binding affinities that are comparable to antibodies.
Authors
Weber, P; Dzuricky, M; Min, J; Jenkins, I; Chilkoti, A
MLA Citation
Weber, Patrick, et al. “Concentration-Independent Multivalent Targeting of Cancer Cells by Genetically Encoded Core-Crosslinked Elastin/Resilin-like Polypeptide Micelles.Biomacromolecules, vol. 22, no. 10, Oct. 2021, pp. 4347–56. Epmc, doi:10.1021/acs.biomac.1c00897.
URI
https://scholars.duke.edu/individual/pub1496497
PMID
34477380
Source
epmc
Published In
Biomacromolecules
Volume
22
Published Date
Start Page
4347
End Page
4356
DOI
10.1021/acs.biomac.1c00897

Author Correction: Cellphone enabled point-of-care assessment of breast tumor cytology and molecular HER2 expression from fine-needle aspirates.

Authors
Joh, DY; Heggestad, JT; Zhang, S; Anderson, GR; Bhattacharyya, J; Wardell, SE; Wall, SA; Cheng, AB; Albarghouthi, F; Liu, J; Oshima, S; Hucknall, AM; Hyslop, T; Hall, AHS; Wood, KC; Shelley Hwang, E; Strickland, KC; Wei, Q; Chilkoti, A
MLA Citation
Joh, Daniel Y., et al. “Author Correction: Cellphone enabled point-of-care assessment of breast tumor cytology and molecular HER2 expression from fine-needle aspirates.Npj Breast Cancer, vol. 7, no. 1, Sept. 2021, p. 126. Pubmed, doi:10.1038/s41523-021-00335-4.
URI
https://scholars.duke.edu/individual/pub1497086
PMID
34535683
Source
pubmed
Published In
Npj Breast Cancer
Volume
7
Published Date
Start Page
126
DOI
10.1038/s41523-021-00335-4

Microphase Separation of Resilin-like and Elastin-like Diblock Copolypeptides in Concentrated Solutions.

Diblock copolymers are valued for their ability to form thin films with nanoscale features that typically reflect those of their microphase-separated structures in concentrated solution. Here, we show that such self-assembled structures can be easily formed with diblock copolymers composed of thermally responsive polypeptides, such as resilin-like polypeptides (RLP) and elastin-like polypeptides (ELP), by exploiting the inverse temperature transition behavior of ELPs in aqueous media. Specifically, we examine the self-assembly of a series of RLP-<i>b</i>-ELP diblock copolypeptides in concentrated aqueous solution (30 and 50 wt %) by small-angle X-ray scattering (SAXS). By systematically varying RLP block length and temperature (10-45 °C), we observed microphase separation into hexagonally packed cylinders and lamellae. By analyzing the observed order-order transitions (OOT) and order-disorder transitions (ODT), we determined that self-assembly in this system is primarily driven by polymer-solvent interactions. While these thermally responsive polymers showed clear ODTs and OOTs at certain temperatures, temperature only had a weak effect on the spacing of the resulting nanostructures. In contrast, we found that nanostructure spacing was far more sensitive to RLP block length. Finally, we used atomic force microscopy (AFM) to demonstrate that spin casting RLP-<i>b</i>-ELP diblock copolypeptides also produce nanostructured thin films with spacings that correlate with those in concentrated solution.
Authors
Navarro, LA; Ryan, JJ; Dzuricky, M; Gradzielski, M; Chilkoti, A; Zauscher, S
MLA Citation
Navarro, Luis A., et al. “Microphase Separation of Resilin-like and Elastin-like Diblock Copolypeptides in Concentrated Solutions.Biomacromolecules, vol. 22, no. 9, Sept. 2021, pp. 3827–38. Epmc, doi:10.1021/acs.biomac.1c00672.
URI
https://scholars.duke.edu/individual/pub1494485
PMID
34387460
Source
epmc
Published In
Biomacromolecules
Volume
22
Published Date
Start Page
3827
End Page
3838
DOI
10.1021/acs.biomac.1c00672

Cellphone enabled point-of-care assessment of breast tumor cytology and molecular HER2 expression from fine-needle aspirates.

Management of breast cancer in limited-resource settings is hindered by a lack of low-cost, logistically sustainable approaches toward molecular and cellular diagnostic pathology services that are needed to guide therapy. To address these limitations, we have developed a multimodal cellphone-based platform-the EpiView-D4-that can evaluate both cellular morphology and molecular expression of clinically relevant biomarkers directly from fine-needle aspiration (FNA) of breast tissue specimens within 1 h. The EpiView-D4 is comprised of two components: (1) an immunodiagnostic chip built upon a "non-fouling" polymer brush-coating (the "D4") which quantifies expression of protein biomarkers directly from crude cell lysates, and (2) a custom cellphone-based optical microscope ("EpiView") designed for imaging cytology preparations and D4 assay readout. As a proof-of-concept, we used the EpiView-D4 for assessment of human epidermal growth factor receptor-2 (HER2) expression and validated the performance using cancer cell lines, animal models, and human tissue specimens. We found that FNA cytology specimens (prepared in less than 5 min with rapid staining kits) imaged by the EpiView-D4 were adequate for assessment of lesional cellularity and tumor content. We also found our device could reliably distinguish between HER2 expression levels across multiple different cell lines and animal xenografts. In a pilot study with human tissue (n = 19), we were able to accurately categorize HER2-negative and HER2-positve tumors from FNA specimens. Taken together, the EpiView-D4 offers a promising alternative to invasive-and often unavailable-pathology services and may enable the democratization of effective breast cancer management in limited-resource settings.
Authors
Joh, DY; Heggestad, JT; Zhang, S; Anderson, GR; Bhattacharyya, J; Wardell, SE; Wall, SA; Cheng, AB; Albarghouthi, F; Liu, J; Oshima, S; Hucknall, AM; Hyslop, T; Hall, AHS; Wood, KC; Shelley Hwang, E; Strickland, KC; Wei, Q; Chilkoti, A
MLA Citation
Joh, Daniel Y., et al. “Cellphone enabled point-of-care assessment of breast tumor cytology and molecular HER2 expression from fine-needle aspirates.Npj Breast Cancer, vol. 7, no. 1, July 2021, p. 85. Pubmed, doi:10.1038/s41523-021-00290-0.
URI
https://scholars.duke.edu/individual/pub1487266
PMID
34215753
Source
pubmed
Published In
Npj Breast Cancer
Volume
7
Published Date
Start Page
85
DOI
10.1038/s41523-021-00290-0