Ashutosh Chilkoti

Indian biomedical engineer

Ashutosh Chilkoti

Born|

India

Nationality| Indian American
Occupation(s)| Biomedical engineer, academic, researcher, and serial entrepreneur
Awards| NSF CAREER Award, National Science Foundation (1998)
Clemson Award for Contributions to the Literature, Society for Biomaterials (2011)
Pritzker Distinguished Lecture Award, Biomedical Engineering Society (2013)
Academic background
Education| B.Tech., Chemical Engineering
Ph.D., Chemical Engineering
Alma mater| Indian Institute of Technology
University of Washington
Academic work
Institutions| Duke University

Ashutosh Chilkoti is an Indian American biomedical engineer, academic, researcher and serial entrepreneur. He is the Alan L. Kaganov Professor of Biomedical Engineering in the Pratt School of Engineering at Duke University.[1]

Chilkoti has published over 350 papers, has been cited 48,000 times, has a Google Scholar H-index of 116 and has 62 US patents awarded. His research is focused on genetically encoded materials and biointerface science and he has pioneered the development of high-throughput and scalable methods for the recombinant synthesis of repetitive polypeptides, invented a method to purify protein drugs without chromatography, and developed a technology for point-of-care clinical diagnostics. He has founded five start-up companies, including PhaseBio Pharmaceuticals in 2002, Sentilus in 2011, Gateway Bio in 2017, Isolere Bio in 2018, and inSoma Bio in 2019.[2]

Chilkoti is a Fellow of American Association for the Advancement of Science,[3] National Academy of Inventors,[4] Biomedical Engineering Society,[5] Controlled Release Society,[6] International Union of Societies for Biomaterials Science and Engineering and American Institute for Medical and Biological Engineering (AIMBE).[7]

## Education

[edit]

Chilkoti obtained his Bachelor of Technology degree in Chemical Engineering from the IIT Delhi in 1985. He pursued his graduate studies at the University of Washington, where he earned his Ph.D. in Chemical Engineering in 1991, and carried out post-doctoral studies in the Center for Bioengineering from 1991 to 1995, also at the University of Washington.[1]

## Career

[edit]

Chilkoti joined Duke University in 1996 as an assistant professor of biomedical engineering. He was promoted to associate professor in 2002 and professor in 2006. He was the Theo Pilkington Chair Professor of Biomedical Engineering from 2008 to 2013, and has been the Alan L. Kaganov Distinguished Professor of Biomedical Engineering at Duke University since 2013.[1]

From 2002 till 2007, Chilkoti served as associate director of the Center for Biologically Inspired Materials and Material Systems at Duke University and was the director of the center from 2007 to 2011. In 2014, he became Chair of the Department of Biomedical Engineering at Duke University and served as chair until 2022. As Chair of the Duke BME department, he launched an incubator—BRiDGE—for Biomedical Engineering faculty and student startups,[8] and he created the Duke Engineering Entrepreneurship program (DEEP)—a post-doctoral fellowship program for recent PhD graduates of the department interested in entrepreneurship.[9] Since 2023, he has been serving as the senior associate dean of Pratt School of Engineering at Duke University.[1]

Chilkoti founded two Gordon Research Conferences (GRCs)—one on Biointerface Science in 2006 and a second on Bioinspired Materials in 2012. Furthermore, he is the founder of five start-ups. These companies include Sentilus, a clinical diagnostics company that was acquired by Immucor in 2014,[10] Phase Bio Pharmaceuticals—a drug delivery company—that had an IPO on NASDAQ in 2018,[11] Isolere Bio—that uses ELPs to purify complex biologics without chromatography—that was acquired by Donaldson in 2023,[12] and inSoma Bio, that has focused on commercializing injectable biomaterials developed in his laboratory for tissue reconstruction.[13]

## Research

[edit]

Chilkoti's research has focused on protein engineering, polymer chemistry, biointerface science, and nanobiotechnology.

### Genetically encoded polymers

[edit]

Chilkoti is most known for his work on genetically engineered elastin-like polypeptides (ELPs), which exhibit thermally responsive behavior and have been exploited by his group to develop new technologies and materials for protein purification,[14] controlled drug release,[15][16] and tissue engineering.[17] He has also pioneered the development of high-throughput and scalable methods for the recombinant synthesis of repetitive peptide polymers that are useful for the recombinant synthesis of ELPs and other repetitive polypeptides.[18][19][20] He developed a new non-chromatographic method for the purification of proteins.[14] He also pioneered the development of injectable depots of ELPs fused to peptide and protein drugs for sustained—week or longer—release,[15] and ELP nanoparticles loaded with small molecule chemotherapeutics for cancer therapy.[16] His research group also developed a new class of partially ordered polypeptides that undergo a phase transition from a liquid into a highly porous solid network at body temperature.[17]

### Intrinsically disordered proteins

[edit]

Using a method for the rapid and multiplexed gene synthesis of repetitive polypeptides, Chilkoti created new variants of ELPs that show phase separation. He then built upon these findings to identify new sequence heuristics that enable the de novo design of repetitive polypeptides that show LCST and UCST phase behavior.[21] He postulated that the low sequence complexity, structural disorder, and phase separation behavior of these repetitive polypeptides make them an interesting class of minimal synthetic intrinsically disordered proteins IDPs (synIDPs), and suggested that these SynIDPs can provide insights into the behavior of other more complex, native IDPs. His group has started to exploit the phase transition behavior of two classes of SynIDPs—ELPs that exhibit LCST phase behavior and resilin-like polypeptides (RLPs) that exhibit UCST phase behavior—to create artificial condensates within cells whose material properties and function can be precisely programmed at the sequence level of the SynIDP to reprogram cellular function by spatio-temporally controlling the flow genetic information and biochemical signals within the cell.[22] His later work on functional artificial condensates of SynIDPs in cells includes sequestration of mRNA in a condensate regulate protein translation,[23] sequestration of an enzyme in an artificial condensate to amplify its activity, sequestration of a plasmid to control gene flow in bacteria[24] and recruitment of the transcriptional machinery to amplify gene expression.[24]

### Next generation PEGylation

[edit]

Chilkoti's research group has developed next-generation polyethylene glycol (PEG)-like conjugates that overcome the immunogenicity issues associated with traditional PEGylation.[25] PEGylation—the attachment of polyethylene glycol (PEG) to biologics—is commonly used to increase their half-life or reduce their immunogenicity, but PEG has itself proven to be antigenic and can elicit a serious anaphylactic response. To overcome these limitations, he designed a new PEG-like stealth hyperbranched polymer that breaks up the long antigenic ethylene glycol sequence in PEG and presents them as much shorter side-chains along a polymer backbone. Peptides and proteins conjugated to this next-generation PEG-like polymer show even longer circulation than PEG conjugates, do not bind to pre-existing anti-PEG antibodies that most people have developed, and do not generate an immune response to this new polymer. He has demonstrated the utility of this technology with a peptide drug for type 2 diabetes,[26] an enzyme drug used to treat gout and an aptamer drug.[27]

### Clinical diagnostics

[edit]

Chilkoti has made contributions to biosensors and clinical diagnostics. His group was the first to demonstrate the use of surface-initiated polymerization to synthesize "nonfouling" polymer brushes from diverse surfaces that completely resist the adsorption of proteins and the adhesion of cells. He then used these nonfouling polymer brushes to develop a protein microarray that enables multiplexed detection of protein analytes with a femtomolar limit-of-detection directly from whole blood.[28] Building upon this work, his group then invented the D4 point-of-care testing (POCT) technology, which enables rapid and accurate disease diagnosis by the quantitative measurement of multiple analytes at sub-picomolar concentrations from a drop of blood without user intervention.[29] This technology led to the formation of a startup company —Sentilus—‚ that was acquired by Immucor in 2014.[10] His group later used the D4 POCT for serology for COVID-19,[30] COVID-19 variant detection,[31] and detection of Ebolavirus.[29]

### Plasmonic biosensors

[edit]

Chilkoti introduced an optical method to quantify biomolecular interactions in real time at the surface of an optically transparent substrate.[32] He used this approach to design a label-free plasmonic biosensor in a chip format. Furthermore, he identified several factors to improve the performance of immobilized metal nanoparticle sensors.[33] Moreover, he also conducted a study to discuss the applications of tunable absorption in designing controlled-emissivity surfaces for thermophotovoltaic devices, producing detector elements for imaging and tailoring an infrared spectrum for controlled thermal dissipation.[34]

## Awards and honors

[edit]

* 1998 - NSF CAREER Award, National Science Foundation
* 2002 - 3M Nontenured Faculty Award, Duke University
* 2005 - Stansell Family Distinguished Research Award, Duke University[35]
* 2007 - Fellow, American Institute for Medical and Biological Engineering (AIMBE)
* 2010 - Humboldt Senior Researcher Award, Alexander von Humboldt Foundation
* 2011 - Clemson Award for “Contributions to the Literature”, Society for Biomaterials[36]
* 2013 - Pritzker Distinguished Lecture Award, Biomedical Engineering Society[37]
* 2013 - Fellow, Biomedical Engineering Society[38]
* 2013 - Fellow, Controlled Release Society
* 2014 - Fellow, National Academy of Inventors[39]
* 2018 - Chandra P. Sharma award, Society for Biomaterials and Artificial Organs (India)[40]
* 2020 - Fellow, American Association for the Advancement of Science
* 2020 - Fellow, Biomaterials Science and Engineering, International Union of Societies for Biomaterials Science and Engineering
* 2022 – Outstanding Postdoc Mentor award, Duke university[41]

## Selected articles

[edit]

* Meyer, D. E., & Chilkoti, A. (1999). Purification of recombinant proteins by fusion with thermally-responsive polypeptides. Nature Biotechnology, 17(11), 1112–1115.
* Nath, N., & Chilkoti, A. (2002). A colorimetric gold nanoparticle sensor to interrogate biomolecular interactions in real time on a surface. Analytical chemistry, 74(3), 504–509.
* Ma, H., Hyun, J. Chilkoti, A. (2004). “Nonfouling” oligoethylene glycol functionalized polymer brushes synthesized by surface-initiated atom transfer radical polymerization. Advanced Materials, 16, 338–341.
* Dreher, M. R., Liu, W., Michelich, C. R., Dewhirst, M. W., Yuan, F., & Chilkoti, A. (2006). Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers. Journal of the National Cancer Institute, 98(5), 335–344.
* Ciracì, C., Hill, R. T., Mock, J. J., Urzhumov, Y., Fernández-Domínguez, A. I., Maier, S. A., ... & Smith, D. R. (2012). Probing the ultimate limits of plasmonic enhancement. Science, 337(6098), 1072–1074.

## References

[edit]

1. ^ a b c d "Ashutosh Chilkoti - Duke". 25 April 2024.
2. ^ "inSoma Bio".
3. ^ "SEVEN FROM DUKE NAMED FELLOWS OF AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE". 26 November 2019.
4. ^ "Fellows List - NAI".
5. ^ "BMES List of Fellows".
6. ^ "Ashutosh Chilkoti, PhD".
7. ^ "ASHUTOSH CHILKOTI, PH.D."
8. ^ "Encouraging Collaborations, Advancing Biomedical Research".
9. ^ "Duke Engineering Entrepreneurship Program".
10. ^ a b "Immucor Acquires Sentilus" (Press release). October 2014.
11. ^ "J&J, AstraZeneca-backed PhaseBio Pharmaceuticals closes downsized IPO".
12. ^ "Donaldson Acquires Isolere Bio, Continuing to Build Life Sciences Business".
13. ^ "inSoma Bio".
14. ^ a b Meyer, D. E.; Chilkoti, A. (1999). "Purification of recombinant proteins by fusion with thermally-responsive polypeptides". Nature Biotechnology. 17 (11): 1112–1115\. doi:10.1038/15100. PMID 10545920.
15. ^ a b Luginbuhl, K. M.; Schaal, J. L.; Umstead, B.; Mastria, E. M.; Li, X.; Banskota, S.; Arnold, S.; Feinglos, M.; d'Alessio, D.; Chilkoti, A. (2017). "One-week glucose control via zero-order release kinetics from an injectable depot of glucagon-like peptide-1 fused to a thermosensitive biopolymer". Nature Biomedical Engineering. 1 (6): 0078. doi:10.1038/s41551-017-0078. PMC 5650111. PMID 29062587.
16. ^ a b Andrew Mackay, J.; Chen, Mingnan; McDaniel, Jonathan R.; Liu, Wenge; Simnick, Andrew J.; Chilkoti, Ashutosh (2009). "Self-assembling chimeric polypeptide–doxorubicin conjugate nanoparticles that abolish tumours after a single injection". Nature Materials. 8 (12): 993–999\. Bibcode:2009NatMa...8..993A. doi:10.1038/nmat2569. PMC 2862348. PMID 19898461.
17. ^ a b Roberts, Stefan; Harmon, Tyler S.; Schaal, Jeffrey L.; Miao, Vincent; Li, Kan; Hunt, Andrew; Wen, Yi; Oas, Terrence G.; Collier, Joel H.; Pappu, Rohit V.; Chilkoti, Ashutosh (2018). "Injectable tissue integrating networks from recombinant polypeptides with tunable order". Nature Materials. 17 (12): 1154–1163\. Bibcode:2018NatMa..17.1154R. doi:10.1038/s41563-018-0182-6. PMC 6329288. PMID 30323334.
18. ^ Tang, Nicholas C.; Chilkoti, Ashutosh (2016). "Combinatorial codon scrambling enables scalable gene synthesis and amplification of repetitive proteins". Nature Materials. 15 (4): 419–424\. Bibcode:2016NatMa..15..419T. doi:10.1038/nmat4521. PMC 4809025. PMID 26726995.
19. ^ Amiram, M.; Quiroz, F. G.; Callahan, D. J.; Chilkoti, A. (2011). "Highly parallel method for synthesis of DNA repeats enables discovery of "smart" protein polymers". Nature Materials. 10 (2): 141–148\. doi:10.1038/nmat2942. PMC 3075872. PMID 21258353.
20. ^ McDaniel, Jonathan R.; MacKay, J. Andrew; Quiroz, Felipe García; Chilkoti, Ashutosh (2010). "Recursive directional ligation by plasmid reconstruction allows rapid and seamless cloning of oligomeric genes". Biomacromolecules. 11 (4): 944–952\. doi:10.1021/bm901387t. PMC 2862688. PMID 20184309.
21. ^ Quiroz, Felipe García; Chilkoti, Ashutosh (2015). "Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers". Nature Materials. 14 (11): 1164–1171\. Bibcode:2015NatMa..14.1164Q. doi:10.1038/nmat4418. PMC 4618764. PMID 26390327.
22. ^ Dai, Yifan; You, Lingchong; Chilkoti, Ashutosh (2023). "Engineering synthetic biomolecular condensates". Nature Reviews Bioengineering. 1 (7): 466–480\. doi:10.1038/s44222-023-00052-6. PMC 10107566. PMID 37359769.
23. ^ Simon, J. R.; Eghtesadi, S. A.; Dzuricky, M.; You, L.; Chilkoti, A. (2019). "Engineered ribonucleoprotein granules inhibit translation in protocells". Molecular Cell. 75 (1): 66–75.e5. doi:10.1016/j.molcel.2019.05.010. PMC 6640848. PMID 31175012.
24. ^ a b Dai, Yifan; Farag, Mina; Lee, Dongheon; Zeng, Xiangze; Kim, Kyeri; Son, Hye-in; Guo, Xiao; Su, Jonathan; Peterson, Nikhil; Mohammed, Javid; Ney, Max; Shapiro, Daniel Mark; Pappu, Rohit V.; Chilkoti, Ashutosh; You, Lingchong (2023). "Programmable synthetic biomolecular condensates for cellular control". Nature Chemical Biology. 19 (4): 518–528\. doi:10.1038/s41589-022-01252-8. PMC 10786170. PMID 36747054.
25. ^ Qi, Y.; Simakova, A.; Ganson, N. J.; Li, X.; Luginbuhl, K. M.; Özer, I.; Liu, W.; Hershfield, M. S.; Matyjaszewski, K.; Chilkoti, A. (2016). "A brush-polymer conjugate of exendin-4 reduces blood glucose for up to five days and eliminates poly(ethylene glycol) antigenicity". Nature Biomedical Engineering. 1. doi:10.1038/s41551-016-0002. PMC 5627778. PMID 28989813.
26. ^ "Injectable non-immunogenic PEG-like conjugate that forms a subcutaneous depot and enables sustained delivery of a peptide drug".
27. ^ Ozer, I.; Kelly, G.; Gu, R.; Li, X.; Zakharov, N.; Sirohi, P.; Nair, S. K.; Collier, J. H.; Hershfield, M. S.; Hucknall, A. M.; Chilkoti, A. (2022). "Polyethylene Glycol-Like Brush Polymer Conjugate of a Protein Drug Does Not Induce an Antipolymer Immune Response and Has Enhanced Pharmacokinetics than Its Polyethylene Glycol Counterpart". Advanced Science. 9 (11): e2103672. doi:10.1002/advs.202103672. PMC 9008788. PMID 35133079.
28. ^ Hucknall, Angus; Kim, Dong-Hwan; Rangarajan, Srinath; Hill, Ryan T.; Reichert, William M.; Chilkoti, Ashutosh (2009). "Simple fabrication of antibody microarrays on non-fouling polymer brushes with femtomolar sensitivity for protein analytes in serum and blood". Advanced Materials. 21 (19): 1968–1971\. Bibcode:2009AdM....21.1968H. doi:10.1002/adma.200803125. PMC 6516072. PMID 31097880.
29. ^ a b Fontes, C. M.; Lipes, B. D.; Liu, J.; Agans, K. N.; Yan, A.; Shi, P.; Cruz, D. F.; Kelly, G.; Luginbuhl, K. M.; Joh, D. Y.; Foster, S. L.; Heggestad, J.; Hucknall, A.; Mikkelsen, M. H.; Pieper, C. F.; Horstmeyer, R. W.; Geisbert, T. W.; Gunn, M. D.; Chilkoti, A. (2021). "Ultrasensitive point-of-care immunoassay for secreted glycoprotein detects Ebola infection earlier than PCR". Science Translational Medicine. 13 (588). doi:10.1126/scitranslmed.abd9696. PMC 8327926. PMID 33827978.
30. ^ Heggestad, J. T.; Kinnamon, D. S.; Olson, L. B.; Liu, J.; Kelly, G.; Wall, S. A.; Oshabaheebwa, S.; Quinn, Z.; Fontes, C. M.; Joh, D. Y.; Hucknall, A. M.; Pieper, C.; Anderson, J. G.; Naqvi, I. A.; Chen, L.; Que, L. G.; Oguin t, 3rd; Nair, S. K.; Sullenger, B. A.; Woods, C. W.; Burke, T. W.; Sempowski, G. D.; Kraft, B. D.; Chilkoti, A. (2021). "Multiplexed, quantitative serological profiling of COVID-19 from blood by a point-of-care test". Science Advances. 7 (26). Bibcode:2021SciA....7.4901H. doi:10.1126/sciadv.abg4901. PMC 8232907. PMID 34172447.`{{cite journal}}`: CS1 maint: numeric names: authors list (link)
31. ^ Heggestad, Jacob T.; Britton, Rhett J.; Kinnamon, David S.; Wall, Simone A.; Joh, Daniel Y.; Hucknall, Angus M.; Olson, Lyra B.; Anderson, Jack G.; Mazur, Anna; Wolfe, Cameron R.; Oguin, Thomas H.; Sullenger, Bruce A.; Burke, Thomas W.; Kraft, Bryan D.; Sempowski, Gregory D.; Woods, Christopher W.; Chilkoti, Ashutosh (2021). "Rapid test to assess the escape of SARS-CoV-2 variants of concern". Science Advances. 7 (49): eabl7682. Bibcode:2021SciA....7.7682H. doi:10.1126/sciadv.abl7682. PMC 8641938. PMID 34860546.
32. ^ Nath, Nidhi; Chilkoti, Ashutosh (2002). "A Colorimetric Gold Nanoparticle Sensor To Interrogate Biomolecular Interactions in Real Time on a Surface". Analytical Chemistry. 74 (3): 504–509\. doi:10.1021/ac015657x. PMID 11838667.
33. ^ Nath, Nidhi; Chilkoti, Ashutosh (2004). "Label-Free Biosensing by Surface Plasmon Resonance of Nanoparticles on Glass: Optimization of Nanoparticle Size". Analytical Chemistry. 76 (18): 5370–5378\. doi:10.1021/ac049741z. PMID 15362894.
34. ^ Moreau, Antoine; Ciracì, Cristian; Mock, Jack J.; Hill, Ryan T.; Wang, Qiang; Wiley, Benjamin J.; Chilkoti, Ashutosh; Smith, David R. (2012). "Controlled-reflectance surfaces with film-coupled colloidal nanoantennas". Nature. 492 (7427): 86–89\. Bibcode:2012Natur.492...86M. doi:10.1038/nature11615. PMC 3584706. PMID 23222613.
35. ^ "Pratt School of Engineering Awards".
36. ^ "Awards and Recognition of Advancements in the Field of Biomaterials".
37. ^ "Robert A. Pritzker Distinguished Lecture Award".
38. ^ "BMES List of Fellows".
39. ^ "2014 Archive – NAI Fellows in the Press". 22 April 2024.
40. ^ "Chandra P. Sharma Award".
41. ^ "Chilkoti named 2022 Outstanding Postdoc Mentor".