Tyler Allen

Positions:

Postdoctoral Associate

Duke Cancer Institute
School of Medicine

Grants:

Publications:

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

Safety and Efficacy of Allogeneic Lung Spheroid Cells in a Mismatched Rat Model of Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis is a devastating interstitial lung disease characterized by the relentless deposition of extracellular matrix causing lung distortions and dysfunctions. The prognosis after detection is merely 3-5 years and the only two Food and Drug Administration-approved drugs treat the symptoms, not the disease, and have numerous side effects. Stem cell therapy is a promising treatment strategy for pulmonary fibrosis. Current animal and clinical studies focus on the use of adipose or bone marrow-derived mesenchymal stem cells. We, instead, have established adult lung spheroid cells (LSCs) as an intrinsic source of therapeutic lung stem cells. In the present study, we compared the efficacy and safety of syngeneic and allogeneic LSCs in immuno-competent rats with bleomycin-induced pulmonary inflammation in an effort to mitigate fibrosis development. We found that infusion of allogeneic LSCs reduces the progression of inflammation and fibrotic manifestation and preserves epithelial and endothelial health without eliciting significant immune rejection. Our study sheds light on potential future developments of LSCs as an allogeneic cell therapy for humans with pulmonary fibrosis. Stem Cells Translational Medicine 2017;9:1905-1916.
Authors
Cores, J; Hensley, MT; Kinlaw, K; Rikard, SM; Dinh, P-U; Paudel, D; Tang, J; Vandergriff, AC; Allen, TA; Li, Y; Liu, J; Niu, B; Chi, Y; Caranasos, T; Lobo, LJ; Cheng, K
MLA Citation
Cores, Jhon, et al. “Safety and Efficacy of Allogeneic Lung Spheroid Cells in a Mismatched Rat Model of Pulmonary Fibrosis.Stem Cells Translational Medicine, vol. 6, no. 10, Oct. 2017, pp. 1905–16. Epmc, doi:10.1002/sctm.16-0374.
URI
https://scholars.duke.edu/individual/pub1471598
PMID
28783251
Source
epmc
Published In
Stem Cells Translational Medicine
Volume
6
Published Date
Start Page
1905
End Page
1916
DOI
10.1002/sctm.16-0374

Derivation of therapeutic lung spheroid cells from minimally invasive transbronchial pulmonary biopsies.

<h4>Background</h4>Resident stem and progenitor cells have been identified in the lung over the last decade, but isolation and culture of these cells remains a challenge. Thus, although these lung stem and progenitor cells provide an ideal source for stem-cell based therapy, mesenchymal stem cells (MSCs) remain the most popular cell therapy product for the treatment of lung diseases. Surgical lung biopsies can be the tissue source but such procedures carry a high risk of mortality.<h4>Methods</h4>In this study we demonstrate that therapeutic lung cells, termed "lung spheroid cells" (LSCs) can be generated from minimally invasive transbronchial lung biopsies using a three-dimensional culture technique. The cells were then characterized by flow cytometry and immunohistochemistry. Angiogenic potential was tested by in-vitro HUVEC tube formation assay. In-vivo bio- distribution of LSCs was examined in athymic nude mice after intravenous delivery.<h4>Results</h4>From one lung biopsy, we are able to derive >50 million LSC cells at Passage 2. These cells were characterized by flow cytometry and immunohistochemistry and were shown to represent a mixture of lung stem cells and supporting cells. When introduced systemically into nude mice, LSCs were retained primarily in the lungs for up to 21 days.<h4>Conclusion</h4>Here, for the first time, we demonstrated that direct culture and expansion of human lung progenitor cells from pulmonary tissues, acquired through a minimally invasive biopsy, is possible and straightforward with a three-dimensional culture technique. These cells could be utilized in long-term expansion of lung progenitor cells and as part of the development of cell-based therapies for the treatment of lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).
Authors
Dinh, P-UC; Cores, J; Hensley, MT; Vandergriff, AC; Tang, J; Allen, TA; Caranasos, TG; Adler, KB; Lobo, LJ; Cheng, K
MLA Citation
Dinh, Phuong-Uyen C., et al. “Derivation of therapeutic lung spheroid cells from minimally invasive transbronchial pulmonary biopsies.Respiratory Research, vol. 18, no. 1, June 2017, p. 132. Epmc, doi:10.1186/s12931-017-0611-0.
URI
https://scholars.duke.edu/individual/pub1471595
PMID
28666430
Source
epmc
Published In
Respiratory Research
Volume
18
Published Date
Start Page
132
DOI
10.1186/s12931-017-0611-0

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

Research Areas:

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