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:

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

Upgrade of a Shared Instrumentation Resource in the PSOE: The Laser Scanning Confocal Microscope

Administered By
Biomedical Engineering
Awarded By
Lord Foundation of North Carolina
Role
Co-Principal Investigator
Start Date
End Date

Publications:

Redirecting Vesicular Transport to Improve Nonviral Delivery of Molecular Cargo

© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Cell engineering relies heavily on viral vectors for the delivery of molecular cargo into cells due to their superior efficiency compared to nonviral ones. However, viruses are immunogenic and expensive to manufacture, and have limited delivery capacity. Nonviral delivery approaches avoid these limitations but are currently inefficient for clinical applications. This work demonstrates that the efficiency of nonviral delivery of plasmid DNA, mRNA, Sleeping Beauty transposon, and ribonucleoprotein can be significantly enhanced through pretreatment of cells with the nondegradable sugars (NDS), such as sucrose, trehalose, and raffinose. The enhancement is mediated by the incorporation of the NDS into cell membranes, causing enlargement of lysosomes and formation of large (>500 nm) amphisome-like bodies (ALBs). The changes in subcellular structures redirect transport of cargo to ALBs rather than to lysosomes, reducing cargo degradation in cells. The data indicate that pretreatment of cells with NDS is a promising approach to improve nonviral cargo delivery in biomedical applications.
Authors
Mao, M; Chang, CC; Pickar-Oliver, A; Cervia, LD; Wang, L; Ji, J; Liton, PB; Gersbach, CA; Yuan, F
MLA Citation
Mao, M., et al. “Redirecting Vesicular Transport to Improve Nonviral Delivery of Molecular Cargo.” Advanced Biosystems, Jan. 2020. Scopus, doi:10.1002/adbi.202000059.
URI
https://scholars.duke.edu/individual/pub1452745
Source
scopus
Published In
Advanced Biosystems
Published Date
DOI
10.1002/adbi.202000059

Enhancing Electrotransfection Efficiency Through Improvement in Nuclear Entry of Plasmid DNA

Authors
Cervia, LD; Chang, C-C; Wang, L; Mao, M; Yuan, F
MLA Citation
Cervia, Lisa D., et al. “Enhancing Electrotransfection Efficiency Through Improvement in Nuclear Entry of Plasmid DNA.” Biophysical Journal, vol. 114, no. 3, CELL PRESS, 2018, pp. 542A-542A.
URI
https://scholars.duke.edu/individual/pub1316175
Source
wos
Published In
Biophysical Journal
Volume
114
Published Date
Start Page
542A
End Page
542A

A self-adaptive sampling digital image correlation algorithm for accurate displacement measurement

© 2014 Elsevier Ltd. All rights reserved. Digital image correlation (DIC) is nowadays widely applied to many engineering areas as an effective optical displacement measurement technique. To minimize the potential effect of spatial sampling locations on full-field displacement measurement, this paper develops a self-adaptive sampling DIC algorithm for accurate and reliable displacement computation over entire specimen surfaces. Depending on local deformation states, the algorithm can automatically optimize spatial distribution of sampling points over specimen surfaces in a self-adaptive manner in combination with the well-developed DIC algorithm with Gaussian windows. Both a series of well-designed computer-simulated speckle images and actual cell-substrate deformation ones are employed to verify the feasibility and effectiveness of the proposed algorithm, which demonstrates that the set of self-adaptive sampling algorithm is capable of recovering more accurate and precise full-field displacements compared to the conventional DIC algorithm with equidistant sampling.
Authors
Yuan, Y; Huang, J; Fang, J; Yuan, F; Xiong, C
MLA Citation
Yuan, Y., et al. “A self-adaptive sampling digital image correlation algorithm for accurate displacement measurement.” Optics and Lasers in Engineering, vol. 65, Feb. 2015, pp. 57–63. Scopus, doi:10.1016/j.optlaseng.2014.05.006.
URI
https://scholars.duke.edu/individual/pub1050019
Source
scopus
Published In
Optics and Lasers in Engineering
Volume
65
Published Date
Start Page
57
End Page
63
DOI
10.1016/j.optlaseng.2014.05.006

A novel Schlemm's Canal scaffold increases outflow facility in a human anterior segment perfusion model.

PURPOSE: An intracanalicular scaffold (Hydrus microstent) designed to reduce intraocular pressure as a glaucoma treatment was tested in human anterior segments to determine changes in outflow facility (C). METHODS: Human eyes with no history of ocular disease or surgeries were perfused within 49 hours of death. The anterior segments were isolated and connected to a perfusion system. Flow rates were measured at pressures of 10, 20, 30, and 40 mm Hg. The scaffold was inserted into Schlemm's canal of the experimental eye, while a control eye underwent a sham procedure. Flow rate measurements were repeated at the four pressure levels. Individual C values were computed by dividing the flow rate by its corresponding pressure, and by averaging the four individual C measurements. The change in C between control and experimental eyes was assessed by the ratio of the baseline and second C measurement. In two eyes, the placement of the scaffold was evaluated histologically. RESULTS: After scaffold implantation in the experimental eyes, the average C increased significantly from baseline (n = 9, P < 0.05). Ratios of C at all pressure levels, except for 10 mm Hg, were significantly higher in experimental eyes (n = 9) than control eyes (P < 0.05, n = 7). Histologically, the scaffold dilated Schlemm's canal with no visible damage to the trabecular meshwork. CONCLUSIONS: The Hydrus Microstent provided an effective way to increase outflow facility in human eyes ex vivo.
Authors
Camras, LJ; Yuan, F; Fan, S; Samuelson, TW; Ahmed, IK; Schieber, AT; Toris, CB
MLA Citation
Camras, Lucinda J., et al. “A novel Schlemm's Canal scaffold increases outflow facility in a human anterior segment perfusion model.Investigative Ophthalmology & Visual Science, vol. 53, no. 10, Jan. 2012, pp. 6115–21. Epmc, doi:10.1167/iovs.12-9570.
URI
https://scholars.duke.edu/individual/pub925663
PMID
22893672
Source
epmc
Published In
Investigative Ophthalmology & Visual Science
Volume
53
Published Date
Start Page
6115
End Page
6121
DOI
10.1167/iovs.12-9570

Dose response of angiogenesis to basic fibroblast growth factor in rat corneal pocket assay: II. Numerical simulations.

Angiogenesis involves interactions among various molecules and cells. To understand the complexity of interactions, we developed a mathematical model to numerically simulate angiogenesis induced by basic fibroblast growth factor (bFGF) in the corneal pocket assay. The model considered interstitial transport of bFGF, cellular uptake of bFGF, and dynamics of vessel growth. The model was validated by comparing simulated vascular networks, induced by bFGF at three different doses: 5 ng, 15 ng, and 50 ng, with experimental data obtained in the first part of the study, in terms of migration distance of vascular network, total vessel length, and number of vessels. The model was also used to simulate growth dynamics of vascular networks as well as spatial and temporal distribution of bFGF, which could not be measured experimentally. Taken together, results of the study suggested that the coupling between diffusion and cellular uptake of bFGF was critical for determining structures of vascular networks and that the mathematical model was appropriate for simulation of angiogenesis in the cornea.
Authors
MLA Citation
Tong, Sheng, and Fan Yuan. “Dose response of angiogenesis to basic fibroblast growth factor in rat corneal pocket assay: II. Numerical simulations.Microvascular Research, vol. 75, no. 1, Jan. 2008, pp. 16–24. Epmc, doi:10.1016/j.mvr.2007.09.005.
URI
https://scholars.duke.edu/individual/pub711215
PMID
18031768
Source
epmc
Published In
Microvascular Research
Volume
75
Published Date
Start Page
16
End Page
24
DOI
10.1016/j.mvr.2007.09.005