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Yifan Yuan, PhD

Academic Title:

Assistant Professor

Primary Appointment:

Anesthesiology

Phone (Primary):

(410) 706-4130

Education and Training

Ph.D. University of Ottawa/Ottawa Hospital Research Institute, Canada

Postdoctoral Associate, Yale University

 

Biosketch

My lab is focused on integrating molecular biology, bioengineering, and computational biology to delineate biological mechanisms in the lung vascular microenvironment and to develop a native-mimicking modeling system during homeostatic and diseased states. 

During my postdoctoral training at Yale School of Medicine, I acquired the necessary skills and expertise in lung and vessel engineering, including bioreactor design, decellularization, recellularization, and animal surgery, to understand the impact of lung vascular microenvironment on cellular functions and phenotypes. I have studied the impact of native lung extracellular matrix on iPSC-derived endothelial cells (iPSC-ECs) functions using our decellularized whole lung scaffolds. Leveraging this system, I developed a novel iPSC-EC-repopulated lung vascular system that can recapitulate some native cellular phenotypes and physiological functions and allow for model inflammatory lung diseases (Yuan et al., Biomaterials. 2019; Yuan et al., Front. Bioeng. Biotechnol., 2021). I also learned single-cell RNA-seq (scRNAseq) and comprehensive computational analysis tools, such as Connectome, to understand cell-cell crosstalk signals in the native lung microvascular niche. In my lab, we will combine the bioengineering and computational tools to study the impact of native cell-cell crosstalk signals and ECM substrates on vascular phenotypes and functions to engineer a native-mimicking lung vascular model system. Additionally, we will also leverage findings from computational analysis of genomics datasets to identify translational drug discovery for lung vascular injury. 

Highlighted Publications

  1. Yuan Y, Altalhi WA, Ng JJ, Stewart DJ, Courtman DW. Derivation of human peripheral blood derived endothelial progenitor cells for biomaterial application: the role of osteopontin surface modification and eNOS transfection. Biomaterials, 2013 Jun 27. pii: S0142-9612(13)00677-7. doi: 10.1016/j.biomaterials.2013.06.003.
  2. Yuan Y, Hunter C, Kallos MS, Sen A. Improved expansion of human bone marrow-derived mesenchymal stem cells in microcarrier-based suspension culture. J Tissue Eng Regen Med. 2014 Mar; 8(3):210-25.
  3. Yuan Y, Engler AJ, Raredon MS, Le A, Baevova P, Yoder MC, Niklason LE. Epac agonist improves barrier function in iPSC-derived endothelial colony forming cells for whole organ tissue engineering. Biomaterials. 2019 Apr;200:25-34. doi: 10.1016/j.biomaterials.2019.02.005. Epub 2019 Feb 7.
  4. Yuan Y. Vascularized lung tissue engineering. Encyclopedia of Tissue Engineering and Regenerative Medicine. 2019, DOI: 10.1016/B978-0-12-801238-3.65562-9.
  5. Raredon MSB, Adams T, Suhail Y, Schupp JC, Poli S, Neumark N, Leiby KL, Greaney AM, Yuan Y, Horien C, Linderman G, Engler AJ, Boffa DJ, Kluger Y, Rosas I, Levchenko A, Kaminski N, Niklason LE. Single-cell connectomic analysis of adult mammalian lung. Science Advances. 2019 Dec 4;5(12):eaaw3851.doi: 10.1126/sciadv.aaw3851.eCollection 2019 Dec.
  6. Yuan Y, Khan S, Stewart DJ, Courtman DW. Engineering blood outgrowth endothelial cells to optimize endothelial nitric oxide synthase and extracellular matrix production for coating of blood contacting surfaces. Acta Biomater. 2020 Apr 14; doi: 10.1016/j.actbio.2020.04.016. [Epub ahead of print] PubMed PMID: 32302726.
  7. Schupp JC, Adams TS, Raredon MSB, Yuan Y, Omote N, Poli S, Chioccioli M, Rose KA, Manning EP, Sauler M, Deluliis G, Ahangari F, Neumark N, Habermann AC, Gutierrez AJ, Bui LT, Lafyatis R, Pierce RW, Meyer KB, Nawijn MC, Teichmann SA, Banovich N, Kropski JA, Niklason LE, Pe’er D, Yan X, Homer R, Rosas IO, Kaminski N. Integrated single cell atlas of endothelial cells for the human lung. Circulation. 2021 May 25. doi: 10.1161/CIRCULATIONAHA.120.052318.
  8. Yuan Y, Leiby KL, Greaney AM, Raredon MBS, Qian H, Schupp JC, Engler AJ, Baevova P, Adams TS, Kural MH, Wang J, Kural M, Wang J, Obata T, Yoder MC, Kaminski N, Niklason LE. A pulmonary vascular model from endothelialized whole organ scaffolds. Front. Bioeng.  2021 Nov 19;9:760309. doi: 10.3389/fbioe.2021.760309. eCollection 2021.
  9. Yuan Y. Clinical translation of engineered pulmonary vascular models. Engineering Translational Models of Lung Homeostasis and Disease. 2023, 10.1007/978-3-031-26625-6

Additional Publication Citations

  1. Yuan Y, Altalhi WA, Ng JJ, Stewart DJ, Courtman DW. Derivation of human peripheral blood derived endothelial progenitor cells for biomaterial application: the role of osteopontin surface modification and eNOS transfection. Biomaterials, 2013 Jun 27. pii: S0142-9612(13)00677-7. doi: 10.1016/j.biomaterials.2013.06.003.
  2. Yuan Y, Hunter C, Kallos MS, Sen A. Improved expansion of human bone marrow-derived mesenchymal stem cells in microcarrier-based suspension culture. J Tissue Eng Regen Med. 2014 Mar; 8(3):210-25.
  3. Lin C, Yuan Y, Courtman DW. Regulation of mouse bone marrow-derived smooth muscle progenitor cells by PDGF-BB and collagen. PLoS One. 2016. 2016 Jun 3;11(6):e0156935. doi: 10.1371/journal.pone.0156935. eCollection 2016.
  4. Yuan Y, Stewart DJ, Courtman DW. The regulation of endothelial nitric oxide synthase by extracellular matrix in human late outgrowth endothelial progenitor cells. Front. Bioeng. Biotechnol. 2016.
  5. Yuan Y, Engler AJ, Raredon MS, Le A, Baevova P, Yoder MC, Niklason LE. Epac agonist improves barrier function in iPSC-derived endothelial colony forming cells for whole organ tissue engineering. Biomaterials. 2019 Apr;200:25-34. doi: 10.1016/j.biomaterials.2019.02.005. Epub 2019 Feb 7.
  6. Kural MH, Wang J, Gui L, Yuan Y, Li G, Leiby KL, Quijano E, Tellides G, Saltzman WM, Niklason LE. Fas ligand and nitric oxide combination to control smooth muscle growth while sparing endothelium. Biomaterials. 2019 Aug;212:28-38. doi: 10.1016/j.biomaterials.2019.05.011. Epub 2019 May 7.
  7. Engler AJ, Raredon MSB, Le A, Yuan Y, Oczkowicz YA, Kan EL, Baevova P, Niklason LE. Non-invasive and real-time measurement of microvascular barrier in intact lungs. Biomaterials. 2019 Oct;217:119313. doi: 10.1016/j.biomaterials.2019.119313. Epub 2019 Jun 30.
  8. Yuan Y. Vascularized lung tissue engineering. Encyclopedia of Tissue Engineering and Regenerative Medicine. 2019, DOI: 10.1016/B978-0-12-801238-3.65562-9.
  9. Cakir B, Xiang Y, Tanaka Y, Kural MH, Parent M, Kang YJ, Chapeton K, Patterson B, Yuan Y, He CS, Raredon MSB, Dengelegi J, Kim KY, Sun P, Zhong M, Lee S, Patra P, Hyder F, Niklason LE, Lee SH, Yoon YS, Park IH. Engineering of human brain organoids with a functional vascular-like system. Nature Methods. 2019 Nov;16(11):1169-1175. doi: 10.1038/s41592-019-0586-5. Epub 2019 Oct 7.
  10. Raredon MSB, Adams T, Suhail Y, Schupp JC, Poli S, Neumark N, Leiby KL, Greaney AM, Yuan Y, Horien C, Linderman G, Engler AJ, Boffa DJ, Kluger Y, Rosas I, Levchenko A, Kaminski N, Niklason LE. Single-cell connectomic analysis of adult mammalian lung. Science Advances. 2019 Dec 4;5(12):eaaw3851.doi: 10.1126/sciadv.aaw3851.eCollection 2019 Dec.
  11. Luo J, Qin L, Zhao L, Gui L, Ellis MW, Huang Y, Kural MH, Clark JA, Ono S, Wang J, Yuan Y, Zhang SM, Cong X, Li G, Riaz M, Lopez C, Hotta A, Campbell S, Tellides G, Dardik A, Niklason LE, Qyang Y. Tissue-engineered vascular grafts with advanced mechanical strength from human iPSCs. Cell Stem Cell. 2020 Feb 6;26(2):251-261.e8. doi: 10.1016/j.stem.2019.12.012. Epub 2020 Jan 16. PubMed PMID: 31956039; PubMed Central PMCID: PMC7021512.
  12. Greaney AM, Adams TS, Brickman Raredon MS, Gubbins E, Schupp JC, Engler AJ, Ghaedi M, Yuan Y, Kaminski N, Niklason LE. Platform effects on regeneration by pulmonary basal cells as evaluated by single-cell RNA sequencing. Cell Rep. 2020 Mar 24;30(12):4250-4265.e6. doi: 10.1016/j.celrep.2020.03.004. PubMed PMID: 32209482.
  13. Dimitrievska S, Wang J, Lin Y, Weyers A, Bai H, Qin L, Li g, Cai C, Kypson A, Kristofik N, Gard A, Sundaram S, Yamamoto K, Wu W, Zhao L, Kural M, Yuan Y, Madri J, Kyriakides TR, Linhardt RJ, Niklason LE. Glycocalyx‐like hydrogel coatings for small diameter vascular grafts. Advanced Functional Materials, 17 April 2020, https://doi.org/10.1002/adfm.201908963
  14. Raredon MSB, Yuan Y, Niklason LE. Lung tissue engineering. Principles of Tissue Engineering 5th Edition. 2020, DOI: https://doi.org/10.1016/C2018-0-03818-9.
  15. Yuan Y, Khan S, Stewart DJ, Courtman DW. Engineering blood outgrowth endothelial cells to optimize endothelial nitric oxide synthase and extracellular matrix production for coating of blood contacting surfaces. Acta Biomater. 2020 Apr 14; doi: 10.1016/j.actbio.2020.04.016. [Epub ahead of print] PubMed PMID: 32302726.
  16. Luo J*, Shi X*, Lin Y*, Yuan Y, Kural MH, Anderson CW, Ellis MW, Riaz M, Niklason LE, Qyang Y. Efficient differentiation of human induced pluripotent stem cells into endothelial cells under xenogeneic-free conditions for vascular tissue engineering. Acta Biomater, 2020 Nov 6;S1742-7061(20)30650-4. doi: 10.1016/j.actbio.2020.11.007. (* co-first author)
  17. Schupp JC, Adams TS, Raredon MSB, Yuan Y, Omote N, Poli S, Chioccioli M, Rose KA, Manning EP, Sauler M, Deluliis G, Ahangari F, Neumark N, Habermann AC, Gutierrez AJ, Bui LT, Lafyatis R, Pierce RW, Meyer KB, Nawijn MC, Teichmann SA, Banovich N, Kropski JA, Niklason LE, Pe’er D, Yan X, Homer R, Rosas IO, Kaminski N. Integrated single cell atlas of endothelial cells for the human lung. Circulation. 2021 May 25. doi: 10.1161/CIRCULATIONAHA.120.052318.
  18. Raredon MSB, Engler AJ, Yuan Y, Greaney AM, Niklason LE. Microvascular fluid flow in ex vivo and engineered lungs. J Appl Physiol. 2021 Sep 23. doi: 10.1152/japplphysiol.00286.2020.
  19. Yuan Y, Leiby KL, Greaney AM, Raredon MBS, Qian H, Schupp JC, Engler AJ, Baevova P, Adams TS, Kural MH, Wang J, Kural M, Wang J, Obata T, Yoder MC, Kaminski N, Niklason LE. A pulmonary vascular model from endothelialized whole organ scaffolds. Front. Bioeng.  2021 Nov 19;9:760309. doi: 10.3389/fbioe.2021.760309. eCollection 2021.
  20. Luo J, Qin L, Park J, Kural MH, Huang Y, Shi X, Riaz M, Wang J, Ellis MW, Anderson CW, Yuan Y, Ren Y, Yoder MC, Tellides G, Niklason LE, Qyang Y. Readily available tissue-engineered vascular grafts derived from human induced pluripotent stem cells. Circ Res. 2022 Feb 22; CIRCRESAHA121320315. doi: 10.1161/CIRCRESAHA.121.320315. Online ahead of print.
  21. Greaney AM, Ramachandra AB, Yuan Y, Korneva A, Humphrey JD, Niklason LE. Decellularization compromises mechanical and structural properties of the native trachea. Biomaterials and Biosystems 2023 Feb 3;9:100074.doi: 10.1016/j.bbiosy.2023.100074.
  22. Leiby KL, Yuan Y, Ng R, Raredon MSB, Adams TS, Baevova P, Greaney AM, Hirschi K, Campbell SG, Kaminski N, Herzog EL, Niklason LE. In vitro engineering of the lung alveolus. npj Regenerative Medicine. (2023) 8:22 ; https://doi.org/10.1038/s41536-023-00295-2
  23. Yuan Y. Clinical translation of engineered pulmonary vascular models. Engineering Translational Models of Lung Homeostasis and Disease. 2023, 10.1007/978-3-031-26625-6
  24. Kim J*, Yuan Y*, Agaronayan K, Zhao A, Wang VD, Gupta G, Essayas H, Kaminski A, McGovern J, Yu S, Woo S, Lee CJ, Saleh T, Hu B, Sun Y, Ishikawa G, Bain W, Evankovich J, Herzog EL, Dela Cruz CS, Ryu C, Sharma L. Damage sensing through TLR9 Promotes Viral Clearance and Recovery During Influenza Infection. bioRxiv (2024), https://doi.org/10.1101/2024.03.04.583378
  25. Obata T, Mizoguchi S, Greaney AM, Adams T, Yuan Y, Edelstein S, Leiby KL, Rivero R, Wang N, Kim H, Yang J, Schupp JC, Stitelman D, Tsuchiya T, Levchenko A, Kaminski N, Niklason LE, Raredon MSB. Organ Boundary Circuits Regulate Sox9+ Alveolar Tuft Cells During Post-Pneumonectomy Lung Regeneration. bioRxiv (2024), https://doi.org/10.1101/2024.01.07.574469

Research Interests

The research in my lab focuses on integrating whole organ tissue engineering, computational biology, systems biology, and biomaterials to develop in vitro modeling systems to elucidate biological mechanisms during disease and development. There are two main research areas: 1) Leveraging multi-omics and molecular biology tools to delineate molecular mechanisms in the lung vascular niche during homeostasis and diseases; 2) Incorporating decellularization/recellularization, bioreactors, multi-omics, and human iPSC to develop vascular and alveolar tissue models for drug screening applications.

Awards and Affiliations

2019

Travel Award, Stem cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases International Conference

2019

Travel and poster award, Gordon Research Conferences, Angiogenesis

2020 - 2021

American Heart Association Postdoctoral Fellowship

2021

Emerging Leader in Regeneration, Janelia Conferences, Howard Hughes

Medical Institute

2022 – 2027               

NIH K99/R00 Pathway to Independence Award

Grants and Contracts

Active Grants

04/01/22 – 03/31/27            

PI Name: Yifan Yuan

Title: Reconstructing native soluble cues in vascularized whole lung scaffolds

Funding Agency: NIH K99/R00 Pathway to Independence Award

Total Cost: $995,506

05/01/24 – 04/30/25            

 

PI Name: Yifan Yuan

Title: Deciphering the novel role of VEGF-D in acute lung injury

Funding Agency: UMB ICTR 2024 Pilot Grant

Total Cost: $50,000

In the News

https://www.medschool.umaryland.edu/anesthesiology/about-us/department-news/2024-news/drs-yifan-yuan-and-konstantin-birukov-win-accelerated-translational-incubator-pilot-award.htm