An average of 150 publications per year are published by investigators who receive tissue from NDRI. Investigator publications cover a broad spectrum of research areas, including cancer, diabetes, cardiovascular, musculoskeletal, neuroscience, and respiratory research. Below is a sample of publications from NDRI investigators in 2021, alongside photos of the investigators themselves.
A full list of publications can be found on NDRI’s website: ndriresource.org/for-researchers/publications.
Diabetes Research
CRISPR-based genome editing in primary human pancreatic islet cells.
Bevacqua RJ, Dai X, Lam JY, Gu X, Friedlander MSH, Tellez K, Miguel-Escalada I, Bonàs-Guarch S, Atla G, Zhao W, Kim SH, Dominguez AA, Qi LS, Ferrer J, MacDonald PE, Kim SK. Nat Commun. 2021 Apr 23;12(1):2397. PMID: 33893274
This research demonstrated successful genome editing in primary human islets using clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9). CRISPR-based targeting efficiently mutated exons and non-coding DNA elements harboring type 2 diabetes (T2D) risk variants. Advances here expand the experimental repertoire for dissecting genetic mechanisms underlying human diabetes and reveal regulatory and genetic mechanisms linking non-coding variants to human diabetes risk.
Ocular Research
Regional Differences and Physiologic Behaviors in Peripapillary Scleral Fibroblasts.
Szeto J, Chow A, McCrea L, Mozzer A, Nguyen TD, Quigley HA, Pitha I. Invest Ophthalmol Vis Sci. 2021 Jan 4;62(1):27. PMID: 33502460
Dr. Pitha and his team investigated cells that are housed within the tough outer wall of the eye – the sclera. Pathologic scleral remodeling underlies potentially blinding diseases such as glaucoma and pathologic myopia. Scleral cells were found to be regionally specialized and closely approximated to the surrounding extracellular matrix. There was a small population of specialized cells called myofibroblasts that were not as closely approximated to their extracellular environment, and these cells could drive scleral remodeling.
Nerve influence on the metabolism of type I and type II diabetic corneal stroma: an in vitro study.
Whelchel AE, Nicholas SE, Ma JX, Karamichos D. Sci Rep. 2021 Jul 1;11(1):13627. PMID: 34211074
The investigators examined the impact of nerves on the metabolic pathways of the corneal stroma. This research is novel in that the impact of innervation in T1DM and T2DM has only previously been examined in epithelial cells and wound healing. The investigators compared the effects of the nerve exerts on cornea stromal metabolism in both Diabetic and non-Diabetic donors, and found a significant alteration in cultures containing both stromal and nerve cells in comparison to stromal only cultures in both Diabetic and non-Diabetic cells; however T1DM and T2DM cellular metabolic pathways were more significantly influenced than their healthy donor counterparts.
Respiratory
Distinct Exosomal mRNA Profiles from BALF and Lung Tissue of COPD and IPF Patients.
Kaur G, Maremanda KP, Campos M, Chand HS, Li F, Hirani N, Haseeb MA, Li D, Rahman I. Int J Mol Sci. 2021 Oct 31;22(21):11830. PMID: 34769265
Using the lung tissues supplied by the NDRI, researchers were able to identify large sets of differentially expressed exosomal mRNAs exosomes in patients with Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis, which can serve as potential biomarkers of therapeutic targets for these debilitating diseases.
Wang Q, Sundar IK, Lucas JH, Muthumalage T, Rahman I. Molecular clock REV-ERBalpha regulates cigarette smoke-induced pulmonary inflammation and epithelial-mesenchymal transition. JCI Insight. 2021 Jun 22;6(12):e145200. PMID: 34014841
In this study using lung tissues provided by the NDRI, researchers were able to identify the mechanism of abnormal epithelial-mesenchymal transition (EMT) regulation by the molecular clock REV-ERBα and its role in the pathogenesis of COPD and circadian rhythm. Activation of REV-ERBα can serve as a novel therapeutic approach for smoking-induced chronic inflammatory lung diseases.
Gonzalez-Gil A, Li TA, Porell RN, Fernandes SM, Tarbox HE, Lee HS, Aoki K, Tiemeyer M, Kim J, Schnaar RL. J Allergy Clin Immunol. 2021 Apr;147(4):1442-1452. PMID: 32791164
Allergic airway diseases, such as asthma and chronic rhinosinusitis, involve errors in the otherwise carefully balanced regulation of airway inflammatory cells. Dr. Gonzalez-Gil and colleagues discovered a species of distinct human molecule secreted from human airway tissues onto the surface of the airways that engages eosinophils and mast cells to regulate allergic processes. These studies provide insights that can lead to previously unanticipated ways to harness inflammatory cells and lessen disease severity.
Rare Disease
Abdelwahab EMM, Bovari-Biri J, Smuk G, Fillinger J, McPhail D, Krymskaya VP, Pongracz JE. Apoptosis. 2021 Jun;26(5-6):253-260. PMID: 33860865
This is a collaborative study between the Laboratory of Rare Lung Diseases at the University Of Pennsylvania School Of Medicine directed by Dr. Vera P. Krymskaya and the Laboratory of Dr. Judit E. Pongracz, Fulbright Scholar, Head of the Department of Pharmaceutical Biotechnology at the University of Pecs, Hungary. The goal of the study was to demonstrate that combined treatment of human LAM cells with low doses of rapamycin, an FDA-approved drug, and the drug candidate Proxison can result in cell death. These important findings suggest that combined inhibition of two cellular pathways can potentially lead to a more effective therapy for LAM.
