science stories

chemical•bio•immunoengineering

My scientific research interests reside at biological boundaries approached with an engineering perspective. Both infectious agents and therapeutic constructs have interactions on the animal, organ, cell, and then the organelle levels for subsequent stories to unfold. This process is not only a story of molecular encounters and interactions, but also a structural and topological one. The narratives of what is foreign and what is innate is questioned, and identities are manipulated to cross these boundaries by passing as self.

 

Research Activities
Defining Immunoengineering Principles for Effective Vaccine Development
Laboratory of Lymphatic and Cancer Bioengineering, Melody A. Swartz

Laboratory for Regenerative Medicine & Pharmacology, Jeffrey A. Hubbell
Senior Scientist
École Polytechnique Fédérale Lausanne (EPFL), Lausanne, Switzerland
2008-2016

  • Establishment of design principles for intradermal vaccine development on the levels of physico-chemical properties, and intracellular, cellular & organ distribution
  • Detailed characterization of resultant neutralizing antibody, B and T cell responses
  • Role of stroma in immunomodulation and vaccine outcomes
  • Hands-on methods development
  • Management of vaccination project for the Bill and Melinda Gates Foundation
  • Management of immunoengineering inter-laboratory group of up to 40 people

Intracellular Trafficking of Non-viral and Viral Vectors
Post-doctoral Fellow
Laboratory of Thomas Weber
Mount Sinai School of Medicine, New York, NY, USA
2000-2007

  • Discovery and Characterization: pH sensitive membrane-active peptides
  • Application of above peptides in non-viral gene delivery
  • Characterisation of particle uptake and traffick in vitro, including aden-associated viruses AAV

Development of Biodegradable Polymer Nanoparticles for Gene Delivery
Doctoral Thesis Research
Laboratories of Robert S. Langer, Richard C. Mulligan
Massachusetts Institute of Technology, The Whitehead Institute, Cambridge, MA, USA
1994-2000

Other short-term projects
Peter’s Bubble
Tribeca Hacks <Story Matter>
CERN, 2014

“Enter the skin of a little boy and show him why diversity is essential.

Peter’s Bubble is one of the shape-shifting stories you can experience on our peer-to-peer storytelling platform. Inspired by the true story of the “Bubble Boy”, a child born without an immune system, it ties deeply into recent developments in immunology that show how our bodies thrive in co-existence with a diversity of microorganisms. The same could also be said of diversity on other scales. Users exchange peer produced video fragments that make up the narrative in Peter’s Bubble.”

Embryonic stem cell lines with tetracycline inducible human growth hormone receptor (Robert D. Rosenberg laboratory, MIT, 1993)

Complex coacervation of chondroitin-4-sulfate, gelatin & streptomycin into microspheres (Kam W. Leong laboratory, The Johns Hopkins University, 1990-1992)

Metabolic product FPLC analysis for coal sulfur removal by thermophilic archaebacteriae (Robert M. Kelley laboratory, The Johns Hopkins University 1989-1990)

Education
Sc.D. MIT 2000
Medical Engineering & Medical Physics
Harvard Medical School/MIT Division of Health Sciences and Technology

B.S. JHU 1992
Biomedical Engineering
Chemical Engineering
The Johns Hopkins University

Select Recent Publications

For a full list, please see the Writings page.

 

Rincon-Restrepo M, Mayer A, Hauert S, Bonner DK, Phelps EA, Hubbell JA, Swartz MA, Hirosue S. (2017) Vaccine nanocarriers: Coupling intracellular pathways and cellular biodistribution to control CD4 vs CD8 T cell responses. Biomaterials, 32:48-58. doi: 10.1016/j.biomaterials.2017.03.047

Cianciaruso, C., Phelps, E. A., Pasquier, M., Hamelin, R., Demurtas, D., Ahmed, M. A., Piemonti, L., Hirosue, S., Swartz, M.A., De Palma, M., Hubbell, J.A., Baekkeskov, S. (2016). Primary Human and Rat Beta Cells Release the Intracellular Autoantigens GAD65, IA-2 and Proinsulin in Exosomes Together with Cytokine-Induced Enhancers of Immunity. Diabetes, db160671. doi: 10.2337/db16-0671
Hirosue, S., J. Dubrot. Modes of antigen presentation by lymph node stromal cells and their immunological implications. Frontiers in Immunology. 2015. doi: 10.3389/fimmu.2015.00446
Hirosue, S., E. Vokali, V. Raghavan, M. Rincon-Restrepo, A.W. Lund, F. Capotosti, P. Corthésy-Henrioud, C. Halin Winter, S. Hugues, M.A. Swartz. Steady-state antigen scavenging, cross-presentation and CD8+ T cell priming: a new role for lymphatic endothelial cells. J Immunol. 2014. doi: 10.4049/jimmunol.1302492
Kourtis, I.C., S. Hirosue, A. de Titta, S. Kontos, T. Stengmann, J.A. Hubbell, M.A.Swartz. Peripherally administered nanoparticles target monocytic myeloid cells in blood, secondary lymphoid organs and tumors. PLoS ONE 2013. doi:10.1371/journal.pone.0061646
Swartz, M.A., S. Hirosue, J.A. Hubbell. Engineering approaches to immunotherapy. Science Translational Medicine 2012. doi: 10.1126/scitranslmed.3003763
Lund, A.W., F.V. Duraes, S. Hirosue, V.R. Raghavan, C. Nembrini, S.N. Thomas, A. Issa, S. Hugues, M.A. Swartz. VEGF-C Promotes Immune Tolerance in B16 Melanomas and Cross-Presentation of Tumor Antigen by Lymph Node Lymphatics. Cell Reports 1(3): pp.191-9, 2012. doi: 10.1016/j.celrep.2012.01.005
Hirosue, S., I.C. Kourtis, J.A. van der Vliés, J.A. Hubbell, M.A. Swartz. Antigen delivery to dendritic cells by poly (propylene sulfide) nanoparticles with disulfide conjugated peptides: Cross-presentation and T cell activation. Vaccine 28(50): pp.7897-7906, 2010doi: 10.1016/j.vaccine.2010.09.077

Older Publications
Hirosue, S., K. Senn, N. Clément, M. Nonnenmacher, L. Gigout, R.M. Linden, T. Weber. Effect of inhibition of Dynein Function and Microtubule-Altering Drugs on AAV2 Transduction. Virology. 10;367(1):10-8, 2007. PMID: 17588632
Hirosue, S., T. Weber. pH-dependent lytic peptides discovered by phage display. Biochemistry, 45 (20): pp. 6476 -6487, 2006. PMID: 16700558
Hirosue, S., B.G. Müller, R.C. Mulligan, R.S. Langer. Plasmid DNA Encapsulation and Release from Solvent Diffusion Nanospheres.  J. Control. Rel. 70: pp. 231-242 , 2001. PMID: 11166423
Dahiyat, B.I., E.M. Posadas, S. Hirosue, E. Hostin, K.W. Leong. Degradable Biomaterials with Elastomeric Characteristics and Drug-carrier Function. React. Polym., 25:2/3, pp.101-109, 1995.
Peeples, T.L., S. Hirosue, G.J. Olson, R.M. Kelly. Coal Sulfur Transformations Monitored by Hyperthermophilic Archaebacteria. Fuel, 70:5, pp.599-604. doi: 10.1016/0016-2361(91)90173-8

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