(7j) Tissue-Engineered Models for Lymphatic and Blood Vascular Biology

My research interest is to understand lymphatic and blood vessel morphogenesis, homeostasis and disease pathogenesis. Toward this end, I am working to develop novel experimental systems and cellular and molecular tools to better understand the mechanisms by which cells regulate and respond to biological and mechanical cues. During my doctoral research in Aleksander S. Popel’s research group at Johns Hopkins University, I explored tumor-lymphatic vessel crosstalk in cancer metastasis using a novel mouse model for rapid onset of metastasis and biochemistry and cell biology methods. In addition, I generated new small peptides to inhibit lymphangiogenesis and angiogenesis using bioinformatics-guided methods, which was confirmed in diverse in vitro and in vivo cancer models. As a postdoctoral fellow in Christopher S. Chen’s research group at Boston University and Harvard Wyss Institute, I am working to complement my expertise in lymphatic and cancer biology with novel organs-on-chip platforms to further extend the focus of my research to biomimetic 3D models of lymphatic and vascular biology. For my postdoctoral research, I am integrating novel 3D microfluidic platforms and cutting-edge molecular and cellular techniques, including cloning, CRISPR-mediated gene editing with in vivo mouse models to develop a novel and unique approach to investigating the mechanisms that contribute to lymphatic and vascular diseases and cancer. Specifically, we have discovered a previously undescribed mechanism by which inflammation impairs lymphatic drainage of fluid and dendritic cells by abnormally tightening the lymphatic junction. The molecular signaling pathway involved in this mechanism is known to be a master regulator of cell and matrix interaction, and I am currently working to investigate this pathway as a mechanism by which inflammation contributes to lymphatic tissue morphogenesis and pathogenesis. In addition, I focus on pancreatic cancer studying how pancreatic cancer cells invade and replace blood endothelium in our 3D tumor-on-chip and in mouse tumor models. This training and my scientific contributions have built a foundation for my long-term research goal of building new tools for investigating the effects of biochemical and physical cues on cell and tissue biology with the eventual goal of informing new and better treatments for lymphatic and vascular diseases and cancer.

SUCCESSFUL PROPOSALS

[1] LE&RN Postdoctoral Fellowship ($94,536.00), Lymphatic Education & Research Network; 2016-2018

[2] TL1 Postdoctoral Fellowship ($47,844.00), NIH/NHLBI; 2015-2016

[3] MOGAM Science Scholarship ($10,000.00), Green Cross (a pharmaceutical company); 2013

PENDING PROPOSAL

[1] K99/R00 NIH Pathway to Independence Award ($1,004,634.00), NIH/NHLBI; (Pending)

POSTDOCTORAL PROJECT

“Lymphatic and blood vessel-on-chip to study lymphatic and blood vessel related diseases such as lymphedema, inflammation, and cancer”

Under the supervision of Christopher S. Chen, Biomedical Engineering, Boston University; The Wyss Institute for Biologically Inspired Engineering, Harvard University

PH.D. DISSERTATION

“Novel role of lymphatic and blood vasculatures in breast cancer growth and metastasis and peptide agents with anti-lymphangiogenic and anti-angiogenic activity”

Under the supervision of Aleksander S. Popel, Department of Biomedical Engineering, Johns Hopkins University School of Medicine.

EDUCATION

2014 Ph.D. Chemical & Biomolecular Engineering, Johns Hopkins University (Mentor: Aleksander Popel)

2008 M.S. Pharmacy, Seoul National University, Korea (Mentor: Youngro Byun)

2006 B.S. (summa cum laude) in Chemical Engineering, Seoul National University, Korea

SELECTED PEER-REVIEWED PUBLICATIONS

(Among 12 first or co-first author publications, 18 total, h-index=11)

[1] Nguyen DHT*, Lee E*, Alimperti SA, Wong A, Eyckmans J, Stanger BZ, Chen CS, “Pancreatic ductal adenocarcinoma replaces endothelium during tissue invasion”, Nat Biomed Eng, 2017, Accepted. *Equal contribution

[2] Lee, E., Song, H.H.G., Chen, C.S., “Biomimetic on-a-chip platforms for studying cancer metastasis”, Curr Opin Chem Eng, 11:20-7, 2016

[3] Lee, E., Fertig, E.J., Jin, K., Sukumar, S., Pandey, N.B., Popel, A.S., “Breast cancer cells condition lymphatic endothelial cells within pre-metastatic niches to promote metastasis”, Nat Commun, 5:4715, 2014

[4] Lee, E., Lee, S.J., Koskimaki, J.E., Han, Z., Pandey, N.B., Popel, A.S., “Inhibition of breast cancer growth and metastasis by a biomimetic peptide”, Sci Rep, 4:7139, 2014

[5] Lee, E., Pandey, N.B., Popel, A.S., “Lymphatic endothelial cells support tumor growth in breast cancer”, Sci Rep, 4:5853, 2014

PATENTS

[1] Popel, A.S., Pandey, N.P., Lee, E., Green, J.J., Shmueli, R.B., “A biomimetic peptide and biodegradable delivery platform for the treatment of angiogenesis- and lymphangiogenesis-dependent diseases”, US Patent 0122390, 2016

[2] Byun, Y., Lee, E., Jeon, O.C., Kim, S.Y., Park, R.W., “Heparin conjugates and methods”, US Patent 8088753, 2012

Teaching Interests:

My previous teaching experiences have given me a sense of how to teach classes and mentor students in the future. As a professor, I will give students necessary tools for developing analytical thinking and to solve problems beyond idiomatic solutions. I will structure classes using a combination of hands-on learning through lab projects as well as reading the current literatures for students to gain an understanding of cutting-edge research. I will also expose students to problems with unknown solutions to challenge them to think critically. I can teach undergraduate students with Chemical Reaction Engineering and Fluid Dynamics or Transport Phenomena in Chemical Engineering. These courses would foster critical thinking, and help students learn the key engineering concepts and their applications in their research. I would be happy to teach topic-oriented courses in Cell and Tissue Engineering, Regenerative Medicine, Cancer, Nanomedicine, and Vascular and Lymphatic Biology for graduate level students.

TEACHING EXPERIENCE

2011-2012 Chemical Kinetic Processes, Johns Hopkins University, MD

2007 Advanced Physical Pharmacy, Seoul National University, Korea

2006 Physical Pharmacy Laboratory, Seoul National University, Korea

MENTORING EXPERIENCE

2017 – Keith Gagnon (M.D., Ph.D. student), Wyss Institute at Harvard University, MA

2015 – 2017 Bryan Hassell (Ph.D. student), Wyss Institute at Harvard University, MA

2013 – 2014 Ryan Walter (undergrad), Biomedical Engineering, Johns Hopkins University, MD

2012 – 2014 Seung-Jae Lee (undergrad), Biomedical Engineering, Johns Hopkins University, MD