Research in the Lai Lab focuses broadly on infectious diseases at mucosal surfaces, targeted drug delivery and nanoparticle-immune interactions using a variety of tools from biophysics, molecular biology, immunology and engineering.

 

Our research is at the interface of engineering, immunology and microbiology, biophysics, and biomaterials — employing both experimental techniques and computational modeling to address a variety of health problems. Below are select examples of ongoing projects.

Please note that we frequently initiate new projects. For an up to date breakdown of ongoing research projects, please contact us.

Mucosal immunology and the mucus barrier

We seek to develop methods to improve protection against infectious diseases at mucosal surfaces. To infect mucosal tissues, such as the lungs, GI tract and female reproductive tract, pathogens must penetrate viscoelastic mucus coatings. We seek to improve our understanding of the interactions between pathogens and mucins, and use this knowledge to develop methods that can better trap pathogens in mucus secretions, which in turn could be readily eliminated via natural mucus clearance mechanisms or other degradative processes, thereby preventing them from infecting cells and tissues in the first place. Two particular areas of interest include harnessing antibody-mucin interactions to crosslink pathogens to mucins as well as tuning the commensal microbial communities.

Antibody response to synthetic nanoparticles

Synthetic polymers are increasingly used in drug delivery and tissue engineering applications. However, how the adaptive immune system can generate antibodies against synthetic polymers remain not well understood. We are currently applying the genetic sequencing and molecular biology techniques to investigate how antibodies can specifically bind to synthetic polymers, the prevalence and ease of induction of such antibodies, and strategies to overcome pre-existing polymer-binding antibodies.

Targeted nanoparticle delivery

Conjugating ligands to nanoparticles for targeted nanoparticle delivery may result in premature elimination from the systemic circulation, thereby limiting the injected dose of particles that can reach target cells/tissues. Furthermore, many disease targets are inherently heterogeneous and not easily targeted by any single ligand. We are investigating ‘pre-targeting’ using bispecific fusion proteins that can crosslink nanoparticles to cells, enabling potentially greater delivery of nanoparticles to more diverse array of cells simultaneously.

Computational modeling

An important theme in our lab is the use of computational modeling to both substantiate our experimental discoveries and guide our experimental efforts to enhance protection against infectious disease or nanoparticle-based drug delivery.

*Co-first author;  Co-corresponding author; § Corresponding author.

Total citations: more than 3900;
H-index: 27
Number of Articles with over 100 citations: 10

  1. McCallen JD*, Schaefer AM*, Lee P*, Hing L, Lai SK§. (2016) Stereolithography-based 3D printed “pillar plates” that minimizes fluid transfers during enzyme linked immunosorbent assays. Annals of Biomedical Engineering.  Accepted.  [Impact 2.9]
  1. Yang Q, Jacobs TM, McCallen JD, Moore DT, Huckaby JT, Edelstein JN, Lai SK§. (2016) Analysis of pre-existing IgG and IgM antibodies against polyethylene glycol (PEG) in the general population. Analytical Chemistry.  PMID: 27804292 DOI: 10.1021/acs.analchem.6b03437.  [Impact 5.6]
  1. Wang YY, Harit D, Subramani DB, Arora H, Kumar P, Lai SK§. (2016) Influenza-binding antibodies immobilize influenza viruses in fresh human airway mucus. European Respiratory Journal.  Accepted.  [Impact 8.3]
  1. Lei M, Newby J, Lin C, Zhang L, Xu F, Kim W, Forest MG, Lai SK, Milowsky M, Wobker S, Huang L. (2016) The Binding Site Barrier Elicited by Tumor Associated Fibroblasts Interferes Disposition of Nanoparticles in Stroma-Vessel Type Tumors. ACS Nano 10 (10): 9243–9258. PMID: 27666558   [Impact 13.3]
  1. Henry C, Wang YY, Yang Q, Hoang T, Hoen T, Ensign L, Nunn KL, Schroeder H, McCallen J, Moench T, Cone R, Roffler S, Lai SK§. (2016) Anti-PEG antibodies alter the mobility and biodistribution of densely PEGylated nanoparticles in mucus. Acta Biomaterialia.  PMID: 27424083, 43:61–70. [Impact 6.0]
  1. Wang YY, Schroeder H, Nunn KL, Woods K, Anderson DJ, Lai SK, Cone RA. (2016) Diffusion of Immunoglobulin G in shed vaginal epithelial cells and in cell-1 free regions of human cervicovaginal mucus. PLoS ONE. 11(6): e0158338. PMCID: PMC4928780[Impact 4.4]
  1. Wessler T, Chen A, McKinley SA, Cone R, Forest MG, Lai SK. (2015) Using computational modeling to optimize the design of antibodies that trap viruses in mucus. ACS Infectious Disease. 2(1):82-92 PMCID: PMC4707974
  1. Yang Q*, Parker C*, McCallen J, Lai SK§. (2015) Addressing challenges of heterogeneous tumor treatment using bispecific protein-mediated pretargeted drug delivery. J Controlled Release. 220(Pt B):715-26  PMCID: PMC4688191 [Impact 7.2]
  1. Wang YY, Nunn KL, McKinley S, Lai SK§. (2015) Minimizing biases associated with tracking analysis of submicron particles in heterogeneous biological fluids.  J Controlled Release.  220(Pt A):37-43.  PMCID: PMC4688199 [Impact 7.2]  {Cited  1}
  1. Nunn KL, Wang YY, Harit D, Humphrys M, Ma B, Cone R, Ravel J, Lai SK§. (2015) Enhanced trapping of HIV-1 by human cervicovaginal mucus is associated with Lactobacillus crispatus-dominant microbiota.  mBio. 6(5):e01084-1 PMCID: PMC4611035  [Impact: 6.8] {Cited 11}

Highlighted in Witkin SS, Linhares IM. 2015. “HIV inhibition by lactobacilli: easier in a test tube than in real life.” mBio 6(5):e01485-15.  mBiosphere: “Lactobacilli present in cervicovaginal mucus alter its protective properties”  Press Release by American Society for Microbiology, “Vaginal microbes influence whether mucus can trap HIV virus”.  Covered by numerous other media outlet, including International Business Times and Slate Magazine.

  1. Chen A, McKinley SA, Shi F, Wang S, Mucha PJ, Harit D, Forest MG, Lai SK§. (2015) Modeling of Virion Collisions in Cervicovaginal Mucus Reveals Limits on Agglutination as the Protective Mechanism of Secretory Immunoglobulin A. PLoS ONE. 10(7):e0131351  PMCID: PMC4488843  [Impact 4.4]   {Cited  3}
  1. Yang Q, Lai SK§. (2015) Emergence, characteristics and unaddressed questions about anti-PEG immunity. WIREs Nanomedicine & Nanobiotechnology (Invited Review).  7(5):655-77. PMCID: PMC4515207  [Impact 4.2] {Cited  27}
  1. McKinley SA, Chen A, Shi F, Wang S, Mucha P, Forest MG, Lai SK. (2014) Modeling neutralization kinetics of HIV-1 by broadly neutralizing monoclonal antibodies in genital secretions coating the cervicovaginal mucosa. PLoS ONE. 9(6):e100598 PMCID: PMC4072659   [Impact 4.4] {Cited 4}
  1. Chen A, McKinley SA, Shi F, Wang S, Mucha P, Forest MG, Lai SK. (2014) Transient antibody-mucin interactions produce a dynamic molecular shield against viral invasion. Biophysical Journal.  106(9):2028-2036. PMCID: PMC4017286  [Impact 3.7]  {Cited 5}
  1. Yang Q, Jones SW, Parker C, Zamboni WC, Jear JE, Lai SK§. (2014) Evading immune cell uptake and clearance requires PEG grafting at densities markedly exceeding the minimum for brush conformation. Molecular Pharmaceutics. 11(4):1250-8 PMID: 24521246  [Impact 4.6]  {Cited 21}
  1. Wang YY*, Kannan A*, Nunn KL, Murphy M, Subramani DB, Moench TM, Cone RA, Lai SK§. (2014) IgG in cervicovaginal mucus traps HSV and prevents vaginal Herpes infections. Mucosal Immunology. 7(5):1036-44 PMCID: PMC4122653  [Impact 7.5]  {Cited 25}

 

  1. Yu T, Chisholm J, Choi WJ, Anonuevo A, Pulicare S, Zhong W, Chen M, Fridley C, Lai SK, Ensign LM, Suk JS, Hanes J. (2016) Mucus‐Penetrating Nanosuspensions for Enhanced Delivery of Poorly Soluble Drugs to Mucosal Surfaces. Advanced Healthcare Materials. 5(21):2745-2750  PMID: 27717163  [Impact 5.8]
  1. Ensign LM, Lai SK, Wang YY, Yang M, Mert O, Hanes J, Cone R. (2014) Pretreatment of Human Cervicovaginal Mucus with Pluronic F127 Enhances Nanoparticle Penetration without Compromising Mucus Barrier Properties to Herpes Simplex Virus. Biomacromolecules. 15(12):4403-9 PMCID: PMC4261994 [Impact 5.4]  {Cited 7}
  1. Yang M*, Lai SK*, Yu T*, Wang YY, Happe C, Zhong W, Zhang M, Anonuevo A, Fridley C, Hung A, Fu J, Hanes J. (2014) Nanoparticle penetration of human cervicovaginal mucus: The effect of polyvinyl alcohol. J Control Release. 192:202-8.  PMCID: PMC4194208  [Impact 7.2]  {Cited 25}
  1. Yang M, Yu T, Wood J, Wang YY, Tang BC, Zeng Q, Simons BW, Fu J, Chuang CM, Lai SK, Wu TC, Hung CF, Hanes J. (2014) Intraperitoneal delivery of paclitaxel by poly(ether-anhydride) microspheres effectively suppresses tumor growth in a murine metastatic ovarian cancer model. Drug Deliv Transl Res. 4(2):203-209. PMCID: PMC3956079. {Cited 3}
  1. Suk JS, Kim AJ, Trehan K, Schneider CS, Cebotaru L, Woodward OM, Boylan NJ, Boyle MP, Lai SK, Guggino WB, Hanes J. (2014) Lung gene therapy with highly compacted DNA nanoparticles that overcome the mucus barrier. J Control Release. 178:8-17. PMCID: PMC3951606 [Impact 7.2]  {Cited 13}
  1. Yang M*, Yu T*, Wang YY, Lai SK, Zeng Q, Miao B, Tang BC, Simons BW, Ensign LM, Liu G, Chan KWY, Juang CY, Mert O, Wood J, Fu J, McMahon MT, Wu TC, Hung CF, Hanes J. (2014) Vaginal delivery of paclitaxel via nanoparticles with non-mucoadhesive surfaces suppresses cervical tumor growth. Advanced Healthcare Materials, 3(7):1044-52. PMCID: PMC4059793 [Impact 5.8] {Cited  29}
  1. Wang YY, Lai SK, Ensign LM, Zhong W, Cone R, Hanes J. (2013) The Microstructure and Bulk Rheology of Human Cervicovaginal Mucus Are Remarkably Resistant to Changes in pH. Biomacromolecules. 14(12):4429-35. PMCID: PMC3918948 [Impact 5.4]   {Cited 10}
  1. Yu T, Wang YY, Yang M, Zhong W, Pulicare S, Choi WJ, Mert O, Fu J, Lai SK, Hanes J. (2012) Biodegradable mucus-penetrating nanoparticles composed of diblock copolymers of polyethylene glycol and poly(lactic-co-glycolic acid). Drug Deliv. Transl. Res. 2 (2), 124-128. PMCID: PMC3818113  {Cited 26}
  1. Boylan NJ*, Kim AJ*, Suk JS, Adstamongkonkul P, Simons BW, Lai SK, Hanes J. (2012) Enhancement of Airway Gene Transfer by DNA Nanoparticles Using A pH-Responsive Block Copolymers of Polyethylene glycol and Poly-L-lysine. Biomaterials. 33:2361-2371 PMCID: PMC3259202 [Impact 7.9] {Cited 29}
  1. Kim AJ, Boylan NJ, Suk JS, Lai SK, Hanes J. (2012) Non-degradative Intracellular Trafficking of Highly Compacted Polymeric DNA Nanoparticles. J Control Release. 158(1):102-7. PMCID: PMC3294172 [Impact 7.2] {Cited 25}
  1. Boylan NJ, Suk JS, Lai SK, Jelinek R, Boyle MP, Cooper MJ, Hanes J. (2012) Highly compacted DNA nanoparticles with low MW PEG coatings: In vitro, ex vivo and in vivo evaluation. J Control Release. 157:72-79. PMCID: PMC3245330 [Impact 7.2] {Cited 36}
  1. Mert O*, Lai SK*, Ensign L, Yang M, Wang YY, Wood J, Hanes J. (2011) A poly(ethylene glycol)-based surfactant for formulation of drug-loaded mucus penetrating particles. J Control Release. 157(3):455-60. PMCID: PMC3246104  [Impact 7.2] {Cited 41}
  1. Suk JS, Boylan NJ, Trehan K, Tang BC, Schneider CS, Lin JM, Boyle MP, Zeitlin PL, Lai SK, Cooper MJ, Hanes J. (2011) N-acetylcysteine Enhances Cystic Fibrosis Sputum Penetration and Airway Gene Transfer by Highly Compacted DNA Nanoparticles. Molecular Therapy. 19(11): 1981–1989. PMCID: PMC3222526   [Impact 7.2] {Cited 41}
  1. Jachak A, Lai SK, Suk JS, Biswal S, Breysse P, Hanes J. (2011) Transport of Metal Oxide Nanoparticles and Single-walled Carbon Nanotubes across Human Mucus. Nanotoxicology. 6(6):614-22. PMCID: PMC4696010 [Impact 3.9] {Cited 16}
  1. Wang YY, Lai SK, So C, Schneider C, Cone R, Hanes J. (2011) Mucoadhesive nanoparticles may disrupt the protective human mucus barrier by altering its microstructure.. PLoS ONE. 6(6): e21547. PMCID: PMC3126822 [Impact 4.4] {Cited 56}
  1. Lai SK, Suk JS, Pace A, Wang YY, Yang M, Mert O, Chen J, Kim J, Hanes J. (2011) Drug carrier nanoparticles that penetrate human chronic rhinosinusitis mucus. Biomaterials. 32(26): 6285-6290. PMCID: PMC3130096 [Impact 7.9] {Cited 55}
  1. Hida K, Lai SK, Suk JS, Won SY, Boyle MP, Hanes J. (2011) Common gene therapy viral vectors do not efficiently penetrate sputum from cystic fibrosis patients. PLoS ONE. 6(5):e19919. PMCID: PMC3103503  [Impact 4.4] {Cited 37}
  1. Yang M*,Lai SK*, Wang YY, Zhong W, Happe C, Zhang M, Fu J, Hanes J. (2011) Biodegradable Nanoparticles Composed Entirely of Safe Materials that Rapidly Penetrate Human Mucus. Angew Chem Int Ed Engl. 50(11):2597-600. PMCID: PMC3100893 [Impact 12.7] {Cited 80}

Listed by Wiley-VCH in “Hot Topics:  Drug Delivery”; “Polymer coat helps nanoparticles penetrate mucus”, Royal Society of Chemistry.

  1. Suk JS, Lai SK, Boylan NJ, Dawson MR, Boyle MP, Hanes J. (2011) Rapid Transport of Muco-inert Nanoparticles in Cystic Fibrosis Sputum Treated with N-acetyl Cysteine. Nanomedicine (Lond). 6(2):365-75  PMCID: PMC3102009  [Impact 6.2] {Cited 63}
  1. Lai SK, Wang YY, Hida K, Cone R, Hanes J. (2010) Nanoparticles reveal that human cervicovaginal mucus is riddled with pores larger than viruses. Proc Natl Acad Sci U S A. 107(2):598-603  PMCID: PMC2818964  [Impact 9.8] {Cited 175}
    Selected for Faculty of 1000 Biology.
  1. Tang BT, Dawson M, Lai SK, Wang YY, Suk JS, Yang M, Zeitlin PL, Boyle MP, Fu J, Hanes J. (2009) Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier. Proc Natl Acad Sci U S A. 106(46):19268-73. PMCID: PMC2780804 [Impact 9.8] {Cited 231}

In this issue, “Mucus is no match for coated nanoparticles”, PNAS; “Biodegradable Particles Can Bypass Mucus, Release Drugs Over Time”, Science Daily; selected for Faculty of 1000 Biology.

  1. Lai SK*, Hida K*, Shukair S, Wang YY, Cone R, Hope TJ, Hanes J. (2009) Human immunodeficiency virus type 1 is trapped by acidic but not by neutralized human cervicovaginal mucus. J Virology. 83:11196-11200.  PMCID: PMC2772788  [Impact 5.2] {Cited 165}
  1. Suk JS*, Lai SK*, Wang YY, Boyle MP, Hanes J (2009). The Penetration of Fresh Undiluted Sputum Expectorated by Cystic Fibrosis Patients by Non-adhesive Polymer Nanoparticles. Biomaterials. 30(13):2591-2597. PMCID: PMC2661768 [Impact 7.9] {Cited 107}
  1. Lai SK*, Wang YY*, Cone R, Wirtz D, Hanes J (2009). Altering mucus rheology to “solidify” human mucus at the nanoscale. PLoS ONE. 4(1): e4294. PMCID: PMC2627937  [Impact 4.4] {Cited 80}
    “A Better Mesh: Researchers ‘Tighten’ Body’s Protective Coating”, Science Daily; featured in over 10 other science/medical news outlets.
  1. Lai SK, Wang YY, Hanes J. (2009) Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv Drug Deliv Rev. 61(2):158-171. PMCID: PMC2667119  [Impact 13.6] {Cited 688}

Featured on the cover

  1. Lai SK, Wang YY, Wirtz D, Hanes J. (2009) Micro- and macrorheology of mucus. Adv Drug Deliv Rev. 61(2):86-100. PMCID: PMC2736374 [Impact 13.6] {Cited 325}
  1. Wang YY*, Lai SK*, Suk JS, Pace A, Cone R, Hanes J. (2008) Addressing the PEG Muco-adhesivity Paradox to Engineer Nanoparticles that “Slip” through the Human Mucus Barrier.
    Angew Chem Int Ed Engl. 47(50):9726-9729. PMCID: PMC2666733   [Impact 12.7] {Cited 260}

News & Views: “Drug delivery: Stealth particles give mucus the slip”, Nature Materials (2009) 8: 11 – 13; News Blog: “Breaking the mucus barrier”, The Scientist (2008); also featured in over 20 other science/medical news outlets.

  1. Lai SK, Hida K, Chen C, Hanes J. (2008) Characterization of the intracellular dynamics of a non-degradative pathway accessed by polymer nanoparticles. J Control Release. 125(2):107-111. PMCID: PMC2220013 [Impact 7.2] {Cited 67}
  1. Lai SK, Hida K, Man ST, Chen C, Machamer C, Schroer TA, Hanes J. (2007) Privileged delivery of polymer nanoparticles to the perinuclear region of live cells via a non-clathrin, non-degradative pathway. Biomaterials. 28(18): 2876-2884. PMID: 17363053  [Impact 7.9] {Cited 205}

Editor’s choice, Drug Discovery Today (2007).

  1. Lai SK, O’Hanlon ED, Harrold S, Man ST, Wang YY, Cone R, Hanes J. (2007) Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus. Proc Natl Acad Sci U S A. 104(5):1482-1487. PMCID: PMC1785284  [Impact 9.8] {Cited 514}
    Research highlights include: “Nanoparticles: Against the flow”, Nature Nanotechnology (2007); “Nanoparticles and mucus”, Journal of American Medical Association (2007) 297(9):941; “Coated Nanoparticles Solve Sticky Drug-Delivery Problem”, National Cancer Institute, Alliance for Nanotechnology in Cancer Newsletter.
  1. Suk JS, Suh J, Lai SK, Hanes J. (2007) Quantifying the intracellular transport of viral and nonviral gene vectors in primary neurons. Exp Biol Med (Maywood). 232(3): 461-9. PMID: 17327481  [Impact 3.0] {Cited 62}
    Society of Experimental Biology & Medicine Best Paper Award for 2007, Basic Biology Section.
  1. Castellanos M, Kushiro K, Lai SK, Shuler ML. (2007) A genomically/chemically complete module for synthesis of lipid membrane in a minimal cell. Biotechnol Bioeng. 97(2):397-409.  PMID: 17149771   [Impact 3.7] {Cited 14}
  1. Suh J, Choy KL, Lai SK, Suk JS, Tang B, Prabhu S, Hanes J. (2007) PEGylation of nanoparticles improves their cytoplasmic transport. Int J Nanomedicine. 2(4):735-41. PMCID: PMC2676827. [Impact 5.0] {Cited 95}
  1. Suk JS, Suh J, Choy K, Lai SK, Fu J, and Hanes J. (2006) Gene delivery to differentiated neurotypic cells with RGD and HIV Tat peptide functionalized polymeric nanoparticles. Biomaterials. 27(29):5143-5150.  PMID: 16769110  [Impact 7.9] {Cited 120}
    Listed in 2006 by Science Direct as a “Top 25 Hottest Article” in the area of Biomaterials (based on times downloaded).
  1. Lai SK, Batra A, Cohen C. (2005) Characterization of polydimethylsiloxane elastomer degradation via cross-linker hydrolysis. Polymer. 46: 4204-4211. [Impact 3.8] {Cited 17}

 

  1. Yang Q, Lai SK. (2016) Engineering well-characterized PEG-coated nanoparticles for elucidating biological barriers to drug delivery. In Cancer Nanotechnology, Methods and Protocols, R Zeineldin (Ed.) Springer. (Methods Mol Biol.)  Invited contribution.
  1. Kim MS, Lai SK. (2011) Mucosal Barriers to Drug- and Gene- Loaded Nanoparticles. In Mass Transport and Biological Barriers to Nanotherapuetics (Chapter 8). R Serda (Ed.) Pan Stanford Publishing, Singapore.
  1. Lai SK, Hanes J. (2007) Real time multiple particle tracking of gene nanocarriers in complex biological environments. In Gene Therapy Protocol, J Ledoux (Ed.), 3rd Ed. The Humana Press, Totowa. (Methods Mol Biol. 2008;434:81-97.) {Cited 11}

 

What’s Snot to Like? – A middle school lesson plan that explores the respiratory and immune systems through mucus. Principal Developers: Nicholas Hoffmann, Amber Vogel. Additional Contributors: Crystal Harden Adams, Samuel K. Lai, Cathy P. Oakes.

What’s Snot to Like? was developed by Morehead Planetarium and Science Center’s DREAMS Initiative with support from the National Science Foundation CAREER Award to Dr. Samuel Lai (Fed. Grant DMR-1151477), and support from the State of North Carolina to Morehead Planetarium and Science Center.

Wang YY*, Kannan A*, Nunn KL, Murphy M, Subramani DB, Moench TM, Cone RA, Lai SK. (2014) IgG in cervicovaginal mucus traps HSV and prevents vaginal Herpes infections. Mucosal Immunology. DOI: 10.1038/mi.2013.120  

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Sam Lai, Ph.D.

(919) 966-3024

lai@unc.edu

Sam Lai, Ph.D., was born in Hong Kong and spent his childhood in both Hong Kong and Vancouver. After completing high school at Phillips Academy, Andover, he attended Cornell University and received his BS in chemical and biomolecular engineering in 2003. He then undertook doctoral studies at Johns Hopkins University, receiving his PhD in chemical and biomolecular engineering in 2007. Following a one-year postdoc, he became a research assistant professor at Johns Hopkins in fall 2008 before joining the UNC Eshelman School of Pharmacy in fall 2010.

Lucas Bouknight


Ashley Buige


Christine Henry


Phoebe Lee


Allison Marvin


Alison Schaefer


Samuel Strader

Graduate Students

Arthi Kannan, MS, 2011-2013


Postdoc

Mike Murphy, PhD, 2011

Multiple openings available immediately.

We are interested in recruiting highly motivated people to join our lab at all levels (postdoctoral fellows, graduate and undergraduate students).

For postdoctoral fellows, preference will be given to those who have a strong background in (1) molecular biology (in particular protein engineering), (2) immunology, or (3) virology. However, we welcome highly creative researchers from all disciplines who are interested in joining a highly dynamic and interdisciplinary group. Competitive candidates are expected to be fully fluent in English, have experience with microscopy, and have a strong record of publications in well-respected journals.

Candidates should send a cover letter and CV to Sam (lai@unc.edu).