Tyler Allen

Positions:

Postdoctoral Associate

Duke Cancer Institute
School of Medicine

Grants:

Publications:

A Regenerative Cardiac Patch Formed by Spray Painting of Biomaterials onto the Heart.

Layering a regenerative polymer scaffold on the surface of the heart, termed as a cardiac patch, has been proven to be effective in preserving cardiac function after myocardial infarction (MI). However, the placement of such a patch on the heart usually needs open-chest surgery, which is traumatic, therefore prevents the translation of this strategy into the clinic. We sought to device a way to apply a cardiac patch by spray painting in situ polymerizable biomaterials onto the heart with a minimally invasive procedure. To prove the concept, we used platelet fibrin gel as the "paint" material in a mouse model of MI. The use of the spraying system allowed for placement of a uniform cardiac patch on the heart in a mini-invasive manner without the need for sutures or glue. The spray treatment promoted cardiac repair and attenuated cardiac dysfunction after MI.
Authors
Tang, J; Vandergriff, A; Wang, Z; Hensley, MT; Cores, J; Allen, TA; Dinh, P-U; Zhang, J; Caranasos, TG; Cheng, K
MLA Citation
Tang, Junnan, et al. “A Regenerative Cardiac Patch Formed by Spray Painting of Biomaterials onto the Heart.Tissue Engineering. Part C, Methods, vol. 23, no. 3, Mar. 2017, pp. 146–55. Epmc, doi:10.1089/ten.tec.2016.0492.
URI
https://scholars.duke.edu/individual/pub1471594
PMID
28068869
Source
epmc
Published In
Tissue Engineering. Part C, Methods
Volume
23
Published Date
Start Page
146
End Page
155
DOI
10.1089/ten.tec.2016.0492

Therapeutic microparticles functionalized with biomimetic cardiac stem cell membranes and secretome.

Stem cell therapy represents a promising strategy in regenerative medicine. However, cells need to be carefully preserved and processed before usage. In addition, cell transplantation carries immunogenicity and/or tumourigenicity risks. Mounting lines of evidence indicate that stem cells exert their beneficial effects mainly through secretion (of regenerative factors) and membrane-based cell-cell interaction with the injured cells. Here, we fabricate a synthetic cell-mimicking microparticle (CMMP) that recapitulates stem cell functions in tissue repair. CMMPs carry similar secreted proteins and membranes as genuine cardiac stem cells do. In a mouse model of myocardial infarction, injection of CMMPs leads to the preservation of viable myocardium and augmentation of cardiac functions similar to cardiac stem cell therapy. CMMPs (derived from human cells) do not stimulate T-cell infiltration in immuno-competent mice. In conclusion, CMMPs act as 'synthetic stem cells' which mimic the paracrine and biointerfacing activities of natural stem cells in therapeutic cardiac regeneration.
Authors
Tang, J; Shen, D; Caranasos, TG; Wang, Z; Vandergriff, AC; Allen, TA; Hensley, MT; Dinh, P-U; Cores, J; Li, T-S; Zhang, J; Kan, Q; Cheng, K
MLA Citation
Tang, Junnan, et al. “Therapeutic microparticles functionalized with biomimetic cardiac stem cell membranes and secretome.Nature Communications, vol. 8, Jan. 2017, p. 13724. Epmc, doi:10.1038/ncomms13724.
URI
https://scholars.duke.edu/individual/pub1471599
PMID
28045024
Source
epmc
Published In
Nature Communications
Volume
8
Published Date
Start Page
13724
DOI
10.1038/ncomms13724

Adult Lung Spheroid Cells Contain Progenitor Cells and Mediate Regeneration in Rodents With Bleomycin-Induced Pulmonary Fibrosis.

<h4>Unlabelled</h4>Lung diseases are devastating conditions and ranked as one of the top five causes of mortality worldwide according to the World Health Organization. Stem cell therapy is a promising strategy for lung regeneration. Previous animal and clinical studies have focused on the use of mesenchymal stem cells (from other parts of the body) for lung regenerative therapies. We report a rapid and robust method to generate therapeutic resident lung progenitors from adult lung tissues. Outgrowth cells from healthy lung tissue explants are self-aggregated into three-dimensional lung spheroids in a suspension culture. Without antigenic sorting, the lung spheroids recapitulate the stem cell niche and contain a natural mixture of lung stem cells and supporting cells. In vitro, lung spheroid cells can be expanded to a large quantity and can form alveoli-like structures and acquire mature lung epithelial phenotypes. In severe combined immunodeficiency mice with bleomycin-induced pulmonary fibrosis, intravenous injection of human lung spheroid cells inhibited apoptosis, fibrosis, and infiltration but promoted angiogenesis. In a syngeneic rat model of pulmonary fibrosis, lung spheroid cells outperformed adipose-derived mesenchymal stem cells in reducing fibrotic thickening and infiltration. Previously, lung spheroid cells (the spheroid model) had only been used to study lung cancer cells. Our data suggest that lung spheroids and lung spheroid cells from healthy lung tissues are excellent sources of regenerative lung cells for therapeutic lung regeneration.<h4>Significance</h4>The results from the present study will lead to future human clinical trials using lung stem cell therapies to treat various incurable lung diseases, including pulmonary fibrosis. The data presented here also provide fundamental knowledge regarding how injected stem cells mediate lung repair in pulmonary fibrosis.
Authors
Henry, E; Cores, J; Hensley, MT; Anthony, S; Vandergriff, A; de Andrade, JBM; Allen, T; Caranasos, TG; Lobo, LJ; Cheng, K
MLA Citation
Henry, Eric, et al. “Adult Lung Spheroid Cells Contain Progenitor Cells and Mediate Regeneration in Rodents With Bleomycin-Induced Pulmonary Fibrosis.Stem Cells Translational Medicine, vol. 4, no. 11, Nov. 2015, pp. 1265–74. Epmc, doi:10.5966/sctm.2015-0062.
URI
https://scholars.duke.edu/individual/pub1471596
PMID
26359426
Source
epmc
Published In
Stem Cells Translational Medicine
Volume
4
Published Date
Start Page
1265
End Page
1274
DOI
10.5966/sctm.2015-0062

Rapid and Efficient Production of Coronary Artery Ligation and Myocardial Infarction in Mice Using Surgical Clips.

<h4>Aims</h4>The coronary artery ligation model in rodents mimics human myocardial infarction (MI). Normally mechanical ventilation and prolonged anesthesia period are needed. Recently, a method has been developed to create MI by popping-out the heart (without ventilation) followed by immediate suture ligation. Mortality is high due to the time-consuming suture ligation process while the heart is exposed. We sought to improve this method and reduce mortality by rapid coronary ligation using a surgical clip instead of a suture.<h4>Methods and results</h4>Mice were randomized into 3 groups: clip MI (CMI), suture MI (SMI), or sham (SHAM). In all groups, heart was manually exposed without intubation through a small incision on the chest wall. Unlike the conventional SMI method, mice in the CMI group received a metal clip on left anterior descending artery (LAD), quickly dispensed by an AutoSuture Surgiclip™. The CMI method took only 1/3 of ligation time of the standard SMI method and improved post-MI survival rate. TTC staining and Masson's trichrome staining revealed a similar degree of infarct size in the SMI and CMI groups. Echocardiograph confirmed that both SMI and CMI groups had a similar reduction of ejection fraction and fraction shortening over the time. Histological analysis showed that the numbers of CD68+ macrophages and apoptotic cells (TUNEL-positive) are indistinguishable between the two groups.<h4>Conclusion</h4>This new method, taking only less than 3 minutes to complete, represents an efficient myocardial infarction model in rodents.
Authors
Andrade, JNBMD; Tang, J; Hensley, MT; Vandergriff, A; Cores, J; Henry, E; Allen, TA; Caranasos, TG; Wang, Z; Zhang, T; Zhang, J; Cheng, K
MLA Citation
Andrade, James NBM de, et al. “Rapid and Efficient Production of Coronary Artery Ligation and Myocardial Infarction in Mice Using Surgical Clips.Plos One, vol. 10, no. 11, Jan. 2015, p. e0143221. Epmc, doi:10.1371/journal.pone.0143221.
URI
https://scholars.duke.edu/individual/pub1471597
PMID
26599500
Source
epmc
Published In
Plos One
Volume
10
Published Date
Start Page
e0143221
DOI
10.1371/journal.pone.0143221

RNA splicing and aggregate gene expression differences in lung squamous cell carcinoma between patients of West African and European ancestry.

OBJECTIVES: Despite disparities in lung cancer incidence and mortality, the molecular landscape of lung cancer in patients of African ancestry remains underexplored, and race-related differences in RNA splicing remain unexplored. MATERIALS AND METHODS: We identified differentially spliced genes (DSGs) and differentially expressed genes (DEGs) in biobanked lung squamous cell carcinoma (LUSC) between patients of West African and European ancestry, using ancestral genotyping and Affymetrix Clariom D array. DSGs and DEGs were validated independently using the National Cancer Institute Genomic Data Commons. Associated biological processes, overlapping canonical pathways, enriched gene sets, and cancer relevance were identified using Gene Ontology Consortium, Ingenuity Pathway Analysis, Gene Set Enrichment Analysis, and CancerMine, respectively. Association with LUSC survival was conducted using The Cancer Genome Atlas. RESULTS: 4,829 DSGs and 267 DEGs were identified, including novel targets in NSCLC as well as genes identified previously to have relevance to NSCLC. RNA splicing events within 3 DSGs as well as 1 DEG were validated in the independent cohort. 853 DSGs and 29 DEGs have been implicated as potential drivers, oncogenes and/or tumor suppressor genes. Biological processes enriched among DSGs and DEGs included metabolic process, biological regulation, and multicellular organismal process and, among DSGs, ion transport. Overlapping canonical pathways among DSGs included neuronal signaling pathways and, among DEGs, cell metabolism involving biosynthesis. Gene sets enriched among DSGs included KRAS Signaling, UV Response, E2 F Targets, Glycolysis, and Coagulation. 355 RNA splicing events within DSGs and 18 DEGs show potential association with LUSC patient survival. CONCLUSION: These DSGs and DEGs, which show potential biological and clinical relevance, could have the ability to drive novel biomarker and therapeutic development to mitigate LUSC disparities.
Authors
Deveaux, AE; Allen, TA; Al Abo, M; Qin, X; Zhang, D; Patierno, BM; Gu, L; Gray, JE; Pecot, CV; Dressman, HK; McCall, SJ; Kittles, RA; Hyslop, T; Owzar, K; Crawford, J; Patierno, SR; Clarke, JM; Freedman, JA
MLA Citation
Deveaux, April E., et al. “RNA splicing and aggregate gene expression differences in lung squamous cell carcinoma between patients of West African and European ancestry.Lung Cancer, vol. 153, Mar. 2021, pp. 90–98. Pubmed, doi:10.1016/j.lungcan.2021.01.015.
URI
https://scholars.duke.edu/individual/pub1472476
PMID
33465699
Source
pubmed
Published In
Lung Cancer
Volume
153
Published Date
Start Page
90
End Page
98
DOI
10.1016/j.lungcan.2021.01.015

Research Areas:

Adult Stem Cells
Cancer
Cancer Disparities
Cell Biology
Mesenchymal stem cells
Metastasis
Stem Cells