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Research Overview

Design and development of three-dimensional bioactive tissue constructs reproducing in vivo immune-physiology to provide fundamental insights into how vaccines, adjuvants, chemicals and biologicals, work in humans.

Research Background

Dr. Sanchez-Schmitz has a dual-major in Chemistry and Biology, with a Masters Degree in Molecular Biology focused on Genetics and a Ph.D. in Immunology focused on Human Bioengineering. During his Ph.D. research work at Mount Sinai School of Medicine in New York City, he tested the effect of microphysiologic hypoxia on the autonomous development of dendritic cells from a human Tissue Construct. Thanks to his experience, he was invited to participate in a small biotech company funded by DARPA to develop a human model for Rapid Vaccine Assessment program. His successful work there produced many patents. After 5 years in industry, Dr. Sanchez-Schmitz was invited to join Dr. Levy at Boston Children’s Hospital and Harvard School of Medicine in 2010 where he was able to focus on his scientific passion: the design and development of human three-dimensional bioactive tissue constructs reproducing in vivo physiology. His new microphysiologic age-specific human Tissue Construct reproduces in vivo primary responses of neonates after in vitro immunization with licensed pediatric vaccines such as HBV, BCG, DTaP, PCV-13, and PCP. His work had helped to secure millions of dollars in grant money from sources such as DARPA, the NIH and Bill & Melinda Gates Foundation. Dr. Sanchez-Schmitz is convinced that better, safer and more efficacious therapeutics for humans can be achieved by focusing pre-clinical selection of candidates on human cells under microphysiological conditions. His breakthrough work could provide fundamental insights into how vaccines, adjuvants, chemicals and biologicals, work in humans. His more than 15 years of relevant experience in cutting-edge scientific research developing predictable in vitro human models that fatefully and reproducibly recapitulate the in vivo physiology of targeted organs, have lead to several peer-review publications, patents, Standard Operating Procedures, grants and sponsored research agreements. “I am extremely honored with the opportunity of been part of Dr. Levy’s Precision Vaccines Program here at Boston Children’s Hospital and Harvard School of Medicine ---Dr. Sanchez-Schmitz”.

Publications

  1. The BNT162b2 mRNA vaccine demonstrates reduced age-associated TH1 support in vitro and in vivo. iScience. 2024 Nov 15; 27(11):111055. View Abstract
  2. Human in vitro modeling of adjuvant formulations demonstrates enhancement of immune responses to SARS-CoV-2 antigen. NPJ Vaccines. 2023 Oct 26; 8(1):163. View Abstract
  3. SOX9 knockout decreases stemness properties in colorectal cancer cells. J Gastrointest Oncol. 2023 Aug 31; 14(4):1735-1745. View Abstract
  4. An extracellular matrix hydrogel from porcine urinary bladder for tissue engineering: In vitro and in vivo analyses. Biomed Mater Eng. 2023; 34(4):331-344. View Abstract
  5. The mRNA vaccine BNT162b2 demonstrates impaired TH1 immunogenicity in human elders in vitro and aged mice in vivo. Res Sq. 2022 Dec 21. View Abstract
  6. Human Newborn Monocytes Demonstrate Distinct BCG-Induced Primary and Trained Innate Cytokine Production and Metabolic Activation In Vitro. Front Immunol. 2021; 12:674334. View Abstract
  7. Neonatal monocytes demonstrate impaired homeostatic extravasation into a microphysiological human vascular model. Sci Rep. 2020 10 20; 10(1):17836. View Abstract
  8. Homozygous deletions implicate non-coding epigenetic marks in Autism spectrum disorder. Sci Rep. 2020 08 20; 10(1):14045. View Abstract
  9. Licensed Bacille Calmette-Guérin (BCG) formulations differ markedly in bacterial viability, RNA content and innate immune activation. Vaccine. 2020 02 24; 38(9):2229-2240. View Abstract
  10. Vascular Endothelium in Neonatal Sepsis: Basic Mechanisms and Translational Opportunities. Front Pediatr. 2019; 7:340. View Abstract
  11. Dynamic molecular changes during the first week of human life follow a robust developmental trajectory. Nat Commun. 2019 03 12; 10(1):1092. View Abstract
  12. Microphysiologic Human Tissue Constructs Reproduce Autologous Age-Specific BCG and HBV Primary Immunization in vitro. Front Immunol. 2018; 9:2634. View Abstract
  13. Microphysiologic Human Tissue Constructs Reproduce Autologous Age-Specific BCG and HBV Primary Immunization in vitro. Frontiers in Immunology. 2018; 2634(9). View Abstract
  14. Toll-like receptor 8 agonist nanoparticles mimic immunomodulating effects of the live BCG vaccine and enhance neonatal innate and adaptive immune responses. J Allergy Clin Immunol. 2017 Nov; 140(5):1339-1350. View Abstract
  15. HLA Alleles are Genetic Markers for Susceptibility and Resistance towards Leprosy in a Mexican Mestizo Population. Ann Hum Genet. 2017 Jan; 81(1):35-40. View Abstract
  16. Genetic polymorphisms of interleukin-1 alpha and the vitamin d receptor in mexican mestizo patients with intervertebral disc degeneration. Int J Genomics. 2014; 2014:302568. View Abstract
  17. Development of newborn and infant vaccines. Sci Transl Med. 2011 Jul 06; 3(90):90ps27. View Abstract
  18. Assessing the immunopotency of Toll-like receptor agonists in an in vitro tissue-engineered immunological model. Immunology. 2010 Jul; 130(3):374-87. View Abstract
  19. An immunologic model for rapid vaccine assessment -- a clinical trial in a test tube. Altern Lab Anim. 2009 Sep; 37 Suppl 1:19-27. View Abstract
  20. Factors and signals that govern the migration of dendritic cells via lymphatics: recent advances. Springer Semin Immunopathol. 2005 Jan; 26(3):273-87. View Abstract
  21. Role of CCR8 and other chemokine pathways in the migration of monocyte-derived dendritic cells to lymph nodes. J Exp Med. 2004 Nov 15; 200(10):1231-41. View Abstract
  22. The CD16(+) (FcgammaRIII(+)) subset of human monocytes preferentially becomes migratory dendritic cells in a model tissue setting. J Exp Med. 2002 Aug 19; 196(4):517-27. View Abstract
  23. CD16+ and CD16- human blood monocyte subsets differentiate in vitro to dendritic cells with different abilities to stimulate CD4+ T cells. Int Immunol. 2001 Dec; 13(12):1571-81. View Abstract
  24. Cis-elements upregulate the activity of the Entamoeba histolytica EhPgp1 gene promoter. Arch Med Res. 2000 Jul-Aug; 31(4 Suppl):S275-6. View Abstract

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