Songli POSITION TITLE: Professor of Bioengineering, University of California, Los Angeles

BIOGRAPHICAL SKETCH

NAME: Song Li eRA COMMONS USER NAME: songli POSITION TITLE: Professor of Bioengineering, University of California, Los Angeles

EDUCATION/TRAINING DEGREE Completion (if Date FIELD OF STUDY INSTITUTION AND LOCATION applicable) MM/YYYY

Peking University, Beijing, P.R.China B.S. 05/1988 Mechanical Engineering Peking University, Beijing, P.R.China M.S. 05/1991 Biomechanics University of California, San Diego Ph.D. 05/1997 Bioengineering University of California, San Diego Postdoc 10/1998 Bioengineering

A. Personal Statement My research is focused on cell engineering, biomaterials and tissue engineering. In the past two decades, my laboratory has made significant contribution to this area. We have engineered biomaterials and stem cells for the regeneration of tissues such as nerve, muscle, blood vessel and spinal cord. Our work also shed light on how biophysical factors regulate stem cell differentiation and cell reprogramming. We have also developed various platforms for immunoengineering applications. I have trained more than 30 Ph.D. students and over 10 postdoctoral fellows, and have collaborated extensively with researchers and clinician scientists on interdisciplinary cutting-edge research. The current application builds logically on my prior work on drug delivery for tissue engineering. I have the expertise, leadership, training, and motivation necessary to successfully carry out the proposed research project.

B. Positions and Honors

Positions and Employment 1998-2000, Assistant Research Scientist (Shu Chien Lab), UC San Diego 2001-2006, Assistant Professor, Department of Bioengineering, UC Berkeley 2006-2011, Associate Professor, Department of Bioengineering, UC Berkeley 2011-2015, Professor, Department of Bioengineering, UC Berkeley 2009-2011, Co-Chair, UC Berkeley-UCSF Bioengineering Graduate Program 2011-2012, Director, Master Program in Bioengineering, UC Berkeley 2011-2012, Co-Director, UC Berkeley-UCSF Master Program in Translational Medicine 2016-current, Chancellor Professor and Chair, Department of Bioengineering, UC Los Angeles 2016-current, Professor, Department of Medicine, UC Los Angeles

Other Professional Experiences  Standing Member of NIH Biomaterials and Biointerface Study Section (2017-2022); Reviewer for >20 domestic and international funding agencies, including National Institute of Health (many study sections such as BTSS, BMBI, BRP, DP2, DP5, ICI, MTE, special panels, SBIR/STTR), National Science Foundation, American Heart Association, American Institute of Biological Sciences, Army, New Jersey Stem Cell Program, Swiss National Science Foundation, Israel Science Foundation, Hong Kong Research Grant Council, and Canada Foundation for Innovation, etc.

 Academic Council, American Institute for Medical and Biological Engineering (AIMBE) (2016-); National Conference Committee, Biomedical Engineering Society (BMES) (2015-2018); Council Member, Cellular and Molecular Bioengineering (CMBE) (2017-2019).  Serve on Editorial boards of multiple scientific journals, including Biofabrication, American Journal of Translational Research, and Frontiers in Biosciences.  Edited 3 books: Stem Cells for Regenerative Medicine, World Scientific Publishing, Inc. (2017); Stem Cells and Tissue Engineering, World Scientific Publishing, Inc. (2011); Protocols for Adult Stem Cells, Humana Press (2010)  Reviewed articles for over 50 scientific journals, including ACS Nano, Advanced Materials, Advanced Functional Materials, Biomaterials, Cell Stem cells, Circulation Research, FASEB Journal, Lab on a Chip, Langmuir, Nano Letters, Nature Biotechnology, Nature Materials, Nature Methods, Nature Nanotechnology, Nature Protocols, PNAS and Tissue Engineering.  Served as Theme, track or session chairs for many conferences, symposium and workshops such as Biomedical Engineering Society Conferences, Experimental Biology Conferences, ASME conferences, Society of Biological Engineering symposium and International Conference of the IEEE Engineering in Medicine and Biology Society.  Program Chair, Biomedical Engineering Society Spring Conference with Experimental Biology, 2013-15  Meeting Chair, Biomedical Engineering Society 2016 National Conference  Meeting Chair, University of California System-wide Bioengineering Symposium, 2017

Selected Honors and Awards  Scientific Development Award, American Heart Association, 1999  Whitaker Foundation Research Award, 2002  Hellman Faculty Award, UC Berkeley, 2004  Keynote speaker, Tissue Engineering and Regenerative Medicine International Society (TERMIS): Stem cells and nanomaterials for tissue regeneration. Seoul, Korea. 9/2009  Winner, VentureLab Competition, UC Berkeley, 2011  Keynote speaker, The 9th World Biomaterials Congress, Chengdu, China, 6/2012  Deloitte QB3 Award for Innovation, 2012  Keynote speaker, The 6th WACBE World Congress, Beijing, 8/2013  Keynote speaker, Tissue Engineering and Regenerative Medicine International Society (TERMIS)-AP, Wuzhen, China, 10/2013  Fellow, American Institute for Medical and Biological Engineering (AIMBE), 2014  Fellow, Biomedical Engineering Society, 2014  Fellow, International Academy for Medical and Biological Engineering, 2015  Chancellor Professor, UCLA, 2015  Shu Chien Lecture, UC Systemwide Bioengineering Symposium, 6/2018  Director-Elect, Bioengineering Institute of California, 2018

C. Contribution to Science

Biomaterials for Tissue Regeneration and Drug Delivery We engineered biomimetic materials with micro/nano structure to recapitulate the in vivo microenvironment of extracellular matrix and promote tissue remodeling and regeneration (Huang et al., Nano Lett, 2006; Patel et al., Nano Lett, 2007; Zhu et al., Tissue Eng, 2011). We also used in situ tissue engineering approach to activate host stem cells by using bioactive factors to facilitate tissue regeneration (Yu et al., Biomaterials, 2012). In addition, we have engineered micro/nano materials for drug release and therapy (Zhu et al., Adv Func Mater, 2010; Downing et al., J Control Release, 2012; Lee et al, Nat Biomed Eng, 2017). a. Huang NF, Patel S, Thakar RG, Wu J, Hsiao BS, Chu B, Lee RJ, Li S (2006) Myotube assembly on nanofibrous and micropatterned polymers. Nano Letters 6(3): 537-542. PMID:16522058 b. Patel S, Kurpinski K, Quigley R, Gao HF, Hsiao BS, Poo MM, and Li S. (2007) Bioactive nanofibers: Synergistic effects of nanotopography and chemical signaling on cell guidance. Nano Letters 7(7):2122- 8. PMID:17567179

c. Zhu Y, Wang A, Patel S, Kurpinski K, Diao E, Bao X, Kwong G, Young W, Li S.(2011) engineering bi- layer nanofibrous conduits for peripheral nerve regeneration. Tissue Eng Part C Methods. 17(7):705-15. PMCID: PMC3124110. d. Yu J, Wang A, Tang Z, Henry J, Li-Ping Lee B, Zhu Y, Yuan F, Huang F, Li S. (2012) The effect of stromal cell-derived factor-1/heparin coating of biodegradable vascular grafts on the recruitment of both endothelial and smooth muscle progenitor cells for accelerated regeneration. Biomaterials 33: 8062-8074. PMCID: PMC3488434 e. Lee K, Conboy M, Park HM, Jiang FG, Kim HJ, Dewitt M A, Mackley VA, Chang K, Rao A, Skinner C, Shobha T, Liu H, Huang WC, Lan F, Bray NL, Li S, Corn JE, Kataoka K, Doudna JA, Conboy I, Murthy N. (2017) Nanoparticle delivery of Cas9 ribonucleoprotein and donor DNA in vivo induces homologous directed DNA repair. Nature Biomedical Engineering. 1:889-901. PMCID: PMC5968829.

Stem Cells and Tissue Regeneration/Remodeling Stem cells have tremendous potential for regenerative medicine applications. We have taken (1) in vitro tissue engineering approach by constructing tissues using stem cells and scaffolds, and (2) in vivo tissue engineering approach to harness the regenerative potential of delivered stem cells or host stem cells. We pioneered in engineering stem cells and micro/nano materials for the regeneration of tissues such as blood vessels, nerve, spinal cord and muscle, e.g., combining mesenchymcal stem cells and nanofibrous materials for vascular graft construction (Hashi et al, PNAS 2007) and delivering neural crest stem cells in nerve conduits for nerve regeneration (Wang et al., Biomaterials, 2011; Huang et al, Sci Rep, 2017). In addition, we used transgenic mice and disease models to elucidate the roles of stem cells in vascular tissue remodeling and disease development (Tang et al., Nat Comm, 2012). a. Hashi CK, Zhu YQ, Yang GY, Young WL, Hsiao BS, Wang K, Chu B, and Li S. (2007) Anti- thrombogenic property of bone marrow mesenchymal stem cells in nanofibrous vascular grafts. Proc Natl Acad Sci U S A. 104(29):11915-20. PMCID: PMC1924591 b. Wang A, Tang Z, Park IH, Zhu Y, Patel S, Daley G, Li S (2011) Induced pluripotent stem cells for neural tissue engineering. Biomaterials 32(22): 5023-32. PMCID: PMC3100451 c. Tang, Z, Wang, A, Yuan, F, Yan, Z, Liu, B, Chu, JS, Helms JA, Li S. (2012) Differentiation of multipotent vascular stem cells contributes to vascular diseases. Nature Communication. June 6; 3: 875. PMCID: PMC3538044 d. Huang CW, Huang WC, Qiu X, Fernandes Ferreira da Silva F, Wang A, Patel S, Nesti LJ, Poo MM, Li S. (2017) The differentiation stage of transplanted stem cells modulates nerve regeneration. Sci Rep. 12;7(1):17401. PMCID: PMC5727226.

Cell Engineering and Mechanobiology Stem cells play important roles in tissue regeneration and disease development. While the effects of biochemical factors on stem cells are widely studied, the regulation of stem cell differentiation and cell reprogramming by the biophysical factors in the microenvironment is much less understood. Our laboratory is among the earliest to demonstrate that the differentiation of mesenchymal stem cells (MSCs) is regulated by biophysical cues such as mechanical strain and substrate stiffness (Kurpinski et al., PNAS 2006; Park et al., Biomaterials 2011). We also demonstrated, for the first time, that biophysical factors such as micro/nano topography and dynamic culture can regulate the epigenetic state and transcriptional factors to promote cell reprogramming from fibroblasts to induced pluripotent stem cells (iPSCs) (Downing et al., Nat Mater 2012; Sia et al., Biomaterials, 2016). a. Kurpinski K, Chu J, Hashi, C, Li S (2006) Anisotropic mechanosensing by mesenchymal stem cells. Proc Natl Acad Sci U S A. 103(44): 16095-16100. PMCID: PMC1637542 b. Park JS, Chu J, Tsou DT, Diop R, Tang Z, Wang A, Li S (2011) The effect of matrix stiffness on the differentiation of mesenchymal stem cells in response to TGF-. Biomaterials 32(16):3921-30. PMCID: PMC3073995 c. Downing T, Soto J, Morez C, Houssin T, Yuan F, Chu J, Fritz A, Patel S, Schaffer D, Li S (2013) Biophysical regulation of epigenetic state and cell reprogramming. Nat Mater 12(12):1154-62. (highlighted in Nat Mater 2013, 12:1082-1083).PMID:24141451

d. Sia J, Sun R, Chu J, Li S. (2016) Dynamic culture improves cell reprogramming efficiency. Biomaterials. 92:36-45. PMID: 27376554.

Complete List of Published Work in MyBibliography: https://www.ncbi.nlm.nih.gov/sites/myncbi/10ueXmkQTqGEru/collections/56146124/public/

D. Research Support

Ongoing Projects

NIH/NHLBI R01HL121450 (PI: Li) 3/2015-3/2020 In Situ Regeneration of Blood Vessel The goal is to investigate the roles of stem cells in the regeneration of blood vessel and how the surface chemistry and porosity of the vascular grafts regulate the remodeling process.

NIH/NHLBI R01HL117213 (PI: Li) 8/2013-5/2019 Stem Cells in Vascular Remodeling The goal is to investigate how vascular stem cells participate in the neointima formation in response to endothelial denudation injury of arteries.

UCLA Broad Stem Cell Research Center Innovation Award (PI: Li) 8/2018-7/2019 Stem cells in tissue remodeling The goal of this seed funding is to investigate the roles of stem cells in tissue regeneration and remodeling in blood vessel and other tissues.

Completed Projects (as PI) in the Past 5 Years

NIH/NIBIB R01EB012240 (PI: Li) 8/2010-5/2014 Multipotent Stem Cells for Tissue Regeneration The goal is to derive neural crest stem cells from induced pluripotent stem cells (iPSCs) and transplant the cells for the regeneration of blood vessels and nerves.

California Institute of Regenerative Medicine (PI: Li) 7/2011-6/2014 Induced Pluripotent Stem Cells for Tissue Regeneration The goal is to unravel the mechanisms (differentiation, paracrine signaling, matrix stiffness) of how induced pluripotent stem cell-derived neural crest stem cells participate in neural tissue regeneration.