Fan Yuan

Overview:

Dr. Yuan's research interests include drug and gene delivery, mechanisms of molecular transport in cells and tissues, and tumor pathophysiology.

Cure of cancer through chemotherapy requires drug molecules to reach all tumor cells at an adequately high concentration. At present, such a requirement cannot be satisfied in most patients. This is because (a) amount of drugs that can be administered into patients is limited by normal tissue tolerance and (b) drug distribution and cellular response to drugs in tumors are heterogeneous. Therefore, cells in regions with drug concentration below the therapeutic level will cause tumor recurrence and they may also develop resistance to future treatment.

The goal of our research is two-fold. One is to improve delivery of therapeutic agents in solid tumors; and the second is to understand mechanisms of drug resistance in tumors caused by intrinsic cellular heterogeneity and physiological barriers. These studies may provide useful information on how to improve clinical treatment of cancer based on currently available drugs or molecular medicines in the future.

Research projects in our lab include quantification of transport parameters, delivery of drugs encapsulated in temperature sensitive liposomes, physical interventions of drugs, electric field-mediated gene delivery, mathematical modeling of drug and gene delivery.

Positions:

Professor of Biomedical Engineering

Biomedical Engineering
Pratt School of Engineering

Professor in Ophthalmology

Ophthalmology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.S. 1983

Peking University (China)

M.S. 1985

Peking University (China)

Ph.D. 1990

City University of New York

Grants:

Pharmacological Sciences Training Program

Administered By
Pharmacology & Cancer Biology
Awarded By
National Institutes of Health
Role
Participating Faculty Member
Start Date
End Date

University Training Program in Biomolecular and Tissue Engineering

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

University Training Program in Biomolecular and Tissue Engineering

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

Intravital point-scanning confocal microscope

Administered By
Biomedical Engineering
Awarded By
National Institutes of Health
Role
Major User
Start Date
End Date

Training in Biomolecular and Tissue Engineering

Administered By
Orthopaedics
Awarded By
National Institutes of Health
Role
Mentor
Start Date
End Date

Publications:

Inhibition of Caspases Improves Non-Viral T Cell Receptor Editing.

T cell receptor (TCR) knockout is a critical step in producing universal chimeric antigen receptor T cells for cancer immunotherapy. A promising approach to achieving the knockout is to deliver the CRISPR/Cas9 system into cells using electrotransfer technology. However, clinical applications of the technology are currently limited by the low cell viability. In this study, we attempt to solve the problem by screening small molecule drugs with an immortalized human T cell line, Jurkat clone E6-1, for inhibition of apoptosis. The study identifies a few caspase inhibitors that could be used to simultaneously enhance the cell viability and the efficiency of plasmid DNA electrotransfer. Additionally, we show that the enhancement could be achieved through knockdown of caspase 3 expression in siRNA treated cells, suggesting that the cell death in electrotransfer experiments was caused mainly by caspase 3-dependent apoptosis. Finally, we investigated if the caspase inhibitors could improve TCR gene-editing with electrotransferred ribonucleoprotein, a complex of Cas9 protein and a T cell receptor-α constant (TRAC)-targeting single guide RNA (sgRNA). Our data showed that inhibition of caspases post electrotransfer could significantly increase cell viability without compromising the TCR disruption efficiency. These new findings can be used to improve non-viral T cell engineering.
Authors
MLA Citation
Wang, Chunxi, et al. “Inhibition of Caspases Improves Non-Viral T Cell Receptor Editing.Cancers, vol. 12, no. 9, Sept. 2020. Epmc, doi:10.3390/cancers12092603.
URI
https://scholars.duke.edu/individual/pub1461009
PMID
32933048
Source
epmc
Published In
Cancers
Volume
12
Published Date
DOI
10.3390/cancers12092603

Enhancing Cell Viability and Efficiency of Plasmid DNA Electrotransfer Through Reducing Plasma Membrane Permeabilization.

<h4>Background</h4>Pulsed electric field has been widely used to facilitate molecular cargo transfer into cells. However, the cell viability is often decreased when trying to increase the electrotransfer efficiency. We hypothesize that the decrease is due to electropermeabilization of cell membrane that disrupts homeostasis of intracellular microenvironment. Thus, a reduction in the membrane permeabilization may increase the cell viability.<h4>Materials and methods</h4>Different compounds were supplemented into the pulsing buffer prior to electrotransfer for reduction of cell membrane damage. Extent of the damage was quantified by leakiness of the membrane to a fluorescent dye, calcein, preloaded into cells. At 24 hours post electrotransfer, cell viability and electrotransfer efficiency were quantified with flow cytometry.<h4>Results</h4>The cell viability could be substantially increased by supplementation of either type B gelatin or bovine serum albumin (BSA), without compromising the electrotransfer efficiency. The supplementation also decreased the amount of calcein leaking out of the cells, suggesting that the improvement in cell viability was due to the reduction in electrotransfer-induced membrane damage.<h4>Conclusion</h4>Data from the study demonstrate that type B gelatin and BSA can be used as inexpensive supplements for improving cell viability in electrotransfer.
Authors
Wang, Y; Chang, C-C; Wang, L; Yuan, F
MLA Citation
Wang, Yanhua, et al. “Enhancing Cell Viability and Efficiency of Plasmid DNA Electrotransfer Through Reducing Plasma Membrane Permeabilization.Bioelectricity, vol. 2, no. 3, Sept. 2020, pp. 251–57. Epmc, doi:10.1089/bioe.2020.0007.
URI
https://scholars.duke.edu/individual/pub1470031
PMID
33344914
Source
epmc
Published In
Bioelectricity
Volume
2
Published Date
Start Page
251
End Page
257
DOI
10.1089/bioe.2020.0007

Gallium Nitride: A Versatile Compound Semiconductor as Novel Piezoelectric Film for Acoustic Tweezer in Manipulation of Cancer Cells

Gallium nitride (GaN) is a compound semiconductor which has advantages to generate new functionalities and applications due to its piezoelectric, pyroelectric, and piezo-resistive properties. Recently, surface acoustic wave (SAW)-based acoustic tweezers were developed as an efficient and versatile tool to manipulate nano- and microparticles aiming for patterning, separating, and mixing biological and chemical components. Conventional piezoelectric materials to fabricate SAW devices such as lithium niobate suffer from its low thermal conductivity and incapability of fabricating multiphysical and integrated devices. This article piloted the development of a GaN-based acoustic tweezer (GaNAT) and its application in manipulating microparticles and biological cells. For the first time, the GaN SAW device was integrated with a microfluidic channel to form an acoustofluidic chip for biological applications. The GaNAT demonstrated its ability to work on high power (up to 10 W) with minimal cooling requirement while maintaining the device temperature below 32°C. Acoustofluidic modeling was successfully applied to numerically study and predict acoustic pressure field and particle trajectories within the GaNAT, which agree well with the experimental results on patterning polystyrene microspheres and two types of biological cells including fibroblast and renal tumor cells. The GaNAT allowed both cell types to maintain high viabilities of 84.5% and 92.1%, respectively.
Authors
Sun, C; Wu, F; Wallis, DJ; Shen, MH; Yuan, F; Yang, J; Wu, J; Xie, Z; Liang, D; Wang, H; Tickle, R; Mikhaylov, R; Clayton, A; Zhou, Y; Wu, Z; Fu, Y; Xun, W; Yang, X
MLA Citation
Sun, C., et al. “Gallium Nitride: A Versatile Compound Semiconductor as Novel Piezoelectric Film for Acoustic Tweezer in Manipulation of Cancer Cells.” Ieee Transactions on Electron Devices, vol. 67, no. 8, Aug. 2020, pp. 3355–61. Scopus, doi:10.1109/TED.2020.3002498.
URI
https://scholars.duke.edu/individual/pub1454443
Source
scopus
Published In
Ieee Transactions on Electron Devices
Volume
67
Published Date
Start Page
3355
End Page
3361
DOI
10.1109/TED.2020.3002498

Correction: Development and characterisation of acoustofluidic devices using detachable electrodes made from PCB.

Correction for 'Development and characterisation of acoustofluidic devices using detachable electrodes made from PCB' by Roman Mikhaylov et al., Lab Chip, 2020, 20, 1807-1814, DOI: 10.1039/C9LC01192G.
Authors
Mikhaylov, R; Wu, F; Wang, H; Clayton, A; Sun, C; Xie, Z; Liang, D; Dong, Y; Yuan, F; Moschou, D; Wu, Z; Shen, MH; Yang, J; Fu, Y; Yang, Z; Burton, C; Errington, RJ; Wiltshire, M; Yang, X
MLA Citation
Mikhaylov, Roman, et al. “Correction: Development and characterisation of acoustofluidic devices using detachable electrodes made from PCB.Lab on a Chip, vol. 20, no. 17, Aug. 2020, p. 3278. Epmc, doi:10.1039/d0lc90070b.
URI
https://scholars.duke.edu/individual/pub1453844
PMID
32735307
Source
epmc
Published In
Lab on a Chip
Volume
20
Published Date
Start Page
3278
DOI
10.1039/d0lc90070b

Development and characterisation of acoustofluidic devices using detachable electrodes made from PCB.

Acoustofluidics has been increasingly applied in biology, medicine and chemistry due to its versatility in manipulating fluids, cells and nano-/micro-particles. In this paper, we develop a novel and simple technology to fabricate a surface acoustic wave (SAW)-based acoustofluidic device by clamping electrodes made using a printed circuit board (PCB) with a piezoelectric substrate. The PCB-based SAW (PCB-SAW) device is systematically characterised and benchmarked with a SAW device made using the conventional photolithography process with the same specifications. Microparticle manipulations such as streaming in droplets and patterning in microchannels were demonstrated in the PCB-SAW device. In addition, the PCB-SAW device was applied as an acoustic tweezer to pattern lung cancer cells to form three or four traces inside the microchannel in a controllable manner. Cell viability of ∼97% was achieved after acoustic manipulation using the PCB-SAW device, which proved its ability as a suitable tool for acoustophoretic applications.
Authors
Mikhaylov, R; Wu, F; Wang, H; Clayton, A; Sun, C; Xie, Z; Liang, D; Dong, Y; Yuan, F; Moschou, D; Wu, Z; Shen, MH; Yang, J; Fu, Y; Yang, Z; Burton, C; Errington, RJ; Wiltshire, M; Yang, X
MLA Citation
Mikhaylov, Roman, et al. “Development and characterisation of acoustofluidic devices using detachable electrodes made from PCB.Lab on a Chip, vol. 20, no. 10, May 2020, pp. 1807–14. Epmc, doi:10.1039/c9lc01192g.
URI
https://scholars.duke.edu/individual/pub1438157
PMID
32319460
Source
epmc
Published In
Lab on a Chip
Volume
20
Published Date
Start Page
1807
End Page
1814
DOI
10.1039/c9lc01192g