Jean-Bosco Tagne, Ph.D.
Faculty and Fellows
Assistant Professor of Medicine
Assistant Professor of Molecular Medicine
Adjunct Professor of Biomedical Engineering
-Associate in Biology: University of Yaoundé, Cameroon,
-BSc Biochemistry & General Microbiology : University of Ouagadougou (BF),
Graduate School Master’s Program:
-MSc Biochemistry and Applied Microbiology: University of Ouagadougou (BF)
-MSc Biotechnology and Biomedical Science: University of Massachusetts, MA
Graduate School PhD Program:
-PhD Biomedical Engineering and Biotechnology: University of Massachusetts, MA with Thesis work done at the Whitehead Institute for Biomedical Research (WIBR)/ MIT Cambridge MA
– Post-Doctoral fellowship in lung development and diseases: Department of Medicine at the Pulmonary Center; Boston University School of Medicine, Boston
. Mechanisms of Lung Development and Cancer
. Sickle Cell Diseases (SCD)
. Endothelial dysfunction and vascular complications in SCD
. Drug Formulations
Targets of the thyroid transcription factor 1 (Ttf1, NKX2-1) a homeodomain necessary for normal lung, thyroid and brain development and other lung regulators in lung development and diseases
One of the main goals of the research in our lab is to identify, characterize and understand the mechanisms of target gene regulation during lung development and related diseases (Cao et al, J. Biol. Chem. 2010). We have used genome-wide approaches (Lee et al, Science. 2002 298 (5594), Harbison CT et al, Nature. 2004 431(7004), Workman C et al, Science 2006 312: 1054) to identify and map targets of the key lung epithelial transcription factor Nkx2.1 in the developing lung. This factor and some of their major targets are being altered in lung diseases such as cancer (Tagne et al, PLoS ONE, 2012, Varma et al, J. Biol. Chem. 2012). Potential links (Tagne et al Respir. Res. 2015 (Highly accessed)) between development and cancer (Millien et all Clin. Exp. Metastasis. 2018, Kathuria Scientific Reports 2018) are now being evaluated as related genes may also uncover novel regulatory mechanisms for therapeutic targeting not only during development but also in other diseases associated with altered levels of Nkx2-1 such as neonatal respiratory distress, Brain-Lung-Thyroid syndrome, and acute respiratory distress syndrome.
Role of Nkx2.1-regulated miRNAs in mouse lung development and diseases
Many miRNAs, small regulatory RNAs that modulate gene expression by translational suppression and degradation of their target mRNAs are important in modulating lung gene expression and differentiation of progenitor cell populations. We characterized potential Nkx2.1-regulated miRNAs identified in microRNA arrays and determined their patterns of expression and their effect in both cell proliferation and differentiation in lung development (Tagne et al Respir. Res. 2015 (Highly accessed)). We are also manipulating their expression in vitro and in vivo to validate their role in regulating lung genes and correlating their expression patterns and downstream targets in development and diseases as these genes may contribute to the abnormal lung phenotypes in Nkx2-1 mutant mouse models we are using a cancer Kras model with the expectation to reveal the underlying mechanisms driving cell proliferation, survival and differentiation in lung development and in lung diseases in which Nkx2-1 levels are altered. As the regulatory mechanisms to be studied in this project are also linked to tumor suppression our findings have the potential to contribute to the understanding, the control, and possible reduction of lung tumor formation as several evidences show that miRNAs play a major role in the regulation of developmental and disease processes.
Use of novel Nano-emulsion technology for drug and miRNAs deliveries
Major challenges for development of a delivery system for miRNAs are the instability and their short biological half-life. To overcome this, one needs to optimize the formulation with smart drug delivery systems made up of complexes particles size of molecules in the sub-micron range referred to as nanoparticles suitable for the treatment of patients.
Using this technology, we have developed a novel Nano base technology drug delivery platform that can deliver a medication contained within these compositions. Our composition is either a liposomal or non-liposomal, stable Nano formulations selectively taken up by cells by exploiting the aspect that the Nano-delivery system is made of natural substances such as oil, surfactants and water, natural non viral gene vector such as chitosan a promising delivery tools for polymer-based nanoparticles or the highly efficient catalyst gold nanoparticles because of their potential applications in biology and medicine. We have successfully used this system to introduce Tamoxifen and Dacarbazine into human cancer cells (Tagne et al, Mol. Pharm. 2008 5(2): 280-6), (Tagne et al, Mol. Pharm. 2008 5(6): 1055-63)) and currently expanding these technologies to facilitate introduction of genes and microRNAs into lung cells (D’Almeida et al BMC Cancer. 2019).
Our lab is also using this technology to deliver Hydroxyurea (HU) for Sickle cell disease (SCD) a complex disorder characterized by clinical heterogeneity and pathologic evidence of intimal hyperplasia, proliferative changes and internal elastic lamina disruption across vascular beds so do Pulmonary hypertension (PH), an independent risk factor for mortality in the suffering patients and other growth factors. We utilize this technology for vascular disorder using endothelial cell in cultures. This represents the first attempt at direct gene manipulation of the endothelium using Nano-technology and promises to advance the therapeutic options for patients. Our design Nano based technology is capable of selectively targeting the cells/organ and delivering a combination of active miRs molecules with some tagged with fluorescent reporter or imaging agent(s) for live imaging.
Our laboratory studies the transcriptional control of gene expression in lung and vascular cells. These studies form the foundation for improved understanding of cellular regulation in lung development and related diseases for an effort to develop new therapies.
NB: Our lab is part of the NANOTHERANOSTIC PLATFORMS FOR CANCER AND VASCULAR DISEASE Boston University ARC with multiple projects.
Course teaching: https://www.bu.edu/academics/eng/courses/eng-be-745/
-Principal Investigator Sickle Cell Lung Disease-Translational-Clinical Research-Vascular-Biology https://www.bumc.bu.edu/pulmonary/research/translational/sicklecelllungdisease/)https://www.bumc.bu.edu/pulmonary/research/basicscienceresearch/vascularbiology/
-Faculty member at the Boston University Nanotechnology Innovation Center (http://www.bu.edu/nano-bu/profile/jean-bosco-tagne/)
Selected peer-reviewed publications:
Please see BU Profile for complete Publications list
Nicolosi, R, Tagne, JB, University of Massachusetts Lowell (WO/2008/016664) Compositions and methods for treating cancer with dacarbazine nanoemulsions.