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:

Distinct Effects of Endosomal Escape and Endosomal Trafficking on Gene Delivery via Electrotransfection

Authors
Cervia, LD; Chang, C-C; Wang, L; Yuan, F
MLA Citation
Cervia, Lisa D., et al. “Distinct Effects of Endosomal Escape and Endosomal Trafficking on Gene Delivery via Electrotransfection.” Biophysical Journal, vol. 112, no. 3, Elsevier BV, 2017, pp. 473a-473a. Crossref, doi:10.1016/j.bpj.2016.11.2539.
URI
https://scholars.duke.edu/individual/pub1262325
Source
crossref
Published In
Biophysical Journal
Volume
112
Published Date
Start Page
473a
End Page
473a
DOI
10.1016/j.bpj.2016.11.2539

Accurate displacement measurement via a self-adaptive digital image correlation method based on a weighted ZNSSD criterion

Digital image correlation (DIC) technique has been increasingly employed to implement surface deformation measurements in many engineering fields. Practically, it has been demonstrated that the choice of subset sizes exerts a strong influence on measurement results of DIC, especially when there exists locally larger deformation over the subsets involved. This paper proposes a novel subpixel registration algorithm with Gaussian windows to implicitly optimize the subset sizes by adjusting the shape of Gaussian windows in a self-adaptive fashion with the aid of a so-called weighted zero-normalized sum-of-squared difference correlation criterion. The feasibility and effectiveness of the self-adaptive algorithm are carefully verified through a set of well-designed synthetic speckle images, which indicates that the presented algorithm is able to greatly enhance the accuracy and precision of displacement measurements as compared with the traditional subpixel registration methods. © 2013 Elsevier Ltd.
Authors
Yuan, Y; Huang, J; Peng, X; Xiong, C; Fang, J; Yuan, F
MLA Citation
Yuan, Y., et al. “Accurate displacement measurement via a self-adaptive digital image correlation method based on a weighted ZNSSD criterion.” Optics and Lasers in Engineering, vol. 52, no. 1, Jan. 2014, pp. 75–85. Scopus, doi:10.1016/j.optlaseng.2013.07.016.
URI
https://scholars.duke.edu/individual/pub967778
Source
scopus
Published In
Optics and Lasers in Engineering
Volume
52
Published Date
Start Page
75
End Page
85
DOI
10.1016/j.optlaseng.2013.07.016

A review of three-dimensional in vitro tissue models for drug discovery and transport studies.

The use of animal models in drug discovery studies presents issues with feasibility and ethical concerns. To address these limitations, in vitro tissue models have been developed to provide a means for systematic, repetitive, and quantitative investigation of drugs. By eliminating or reducing the need for animal subjects, these models can serve as platforms for more tightly controlled, high-throughput screening of drugs and for pharmacokinetic and pharmacodynamic analyses of drugs. The focus of this review is three-dimensional (3D) tissue models that can capture cell-cell and cell-matrix interactions. Compared to the 2D culture of cell monolayers, 3D models more closely mimic native tissues since the cellular microenvironment established in the 3D models often plays a significant role in disease progression and cellular responses to drugs. A growing body of research has been published in the literature, which highlights the benefits of the 3D in vitro models of various tissues. This review provides an overview of some successful 3D in vitro models that have been developed to mimic liver, breast, cardiac, muscle, bone, and corneal tissues as well as malignant tissues in solid tumors.
Authors
Elliott, NT; Yuan, F
MLA Citation
Elliott, Nelita T., and Fan Yuan. “A review of three-dimensional in vitro tissue models for drug discovery and transport studies..” Journal of Pharmaceutical Sciences, vol. 100, no. 1, Jan. 2011, pp. 59–74. Epmc, doi:10.1002/jps.22257.
URI
https://scholars.duke.edu/individual/pub807829
PMID
20533556
Source
epmc
Published In
Journal of Pharmaceutical Sciences
Volume
100
Published Date
Start Page
59
End Page
74
DOI
10.1002/jps.22257

Electric fields around and within single cells during electroporation-a model study.

One of the key issues in electric field-mediated molecular delivery into cells is how the intracellular field is altered by electroporation. Therefore, we simulated the electric field in both the extracellular and intracellular domains of spherical cells during electroporation. The electroporated membrane was modeled macroscopically by assuming that its electric resistivity was smaller than that of the intact membrane. The size of the electroporated region on the membrane varied from zero to the entire surface of the cell. We observed that for a range of values of model constants, the intracellular current could vary several orders of magnitude whereas the maximum variations in the extracellular and total currents were less than 8% and 4%, respectively. A similar difference in the variations was observed when comparing the electric fields near the center of the cell and across the permeabilized membrane, respectively. Electroporation also caused redirection of the extracellular field that was significant only within a small volume in the vicinity of the permeabilized regions, suggesting that the electric field can only facilitate passive cellular uptake of charged molecules near the pores. Within the cell, the field was directed radially from the permeabilized regions, which may be important for improving intracellular distribution of charged molecules.
Authors
Mossop, BJ; Barr, RC; Henshaw, JW; Yuan, F
MLA Citation
Mossop, Brian J., et al. “Electric fields around and within single cells during electroporation-a model study..” Annals of Biomedical Engineering, vol. 35, no. 7, July 2007, pp. 1264–75. Epmc, doi:10.1007/s10439-007-9282-1.
URI
https://scholars.duke.edu/individual/pub711214
PMID
17340194
Source
epmc
Published In
Annals of Biomedical Engineering
Volume
35
Published Date
Start Page
1264
End Page
1275
DOI
10.1007/s10439-007-9282-1

Numerical simulations of transcorneal tranport of ethacrynic acid

Potential trabecular meshwork (TM) drugs can be delivered with a lower concentration on the cornea surface over a long period of time for reducing the induced corneal toxicity. To determine the concentration of drugs that can be achieved in the TM, we developed a mathematical model to simulate axisymmetric transport of ethacrynic acid (ECA) from the cornea surface to the TM in a human eye. The results showed that the concentration of ECA could reach the therapeutic level at the TM site while the concentration of ECA on the cornea surface was maintained at an optimal level (75 μM) below the toxicity threshold. These results can be used to guide the design of controlled drug release devices.
Authors
MLA Citation
Lin, C. W., and F. Yuan. “Numerical simulations of transcorneal tranport of ethacrynic acid.” Proceedings of the 2005 Summer Bioengineering Conference, vol. 2005, Dec. 2005, pp. 289–90.
URI
https://scholars.duke.edu/individual/pub807834
Source
scopus
Published In
Proceedings of the 2005 Summer Bioengineering Conference
Volume
2005
Published Date
Start Page
289
End Page
290