Selected Grantee Publications
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- 64 results found
- nci
- Vaccines/Therapeutics
Acoustofluidic Rotational Tweezing Enables High-Speed Contactless Morphological Phenotyping of Zebrafish Larvae
Chen et al., Nature Communications. 2021.
https://pubmed.ncbi.nlm.nih.gov/33602914/
These authors demonstrate an acoustofluidic rotational tweezing platform that enables contactless, high-speed, 3D multispectral imaging and digital reconstruction of zebrafish larvae for quantitative phenotypic analysis. The acoustic-induced polarized vortex streaming achieves contactless and rapid (~1 s/rotation) rotation of zebrafish larvae enabling multispectral imaging of the zebrafish body and internal organs. They developed a 3D reconstruction pipeline that yields accurate 3D models based on the multi-view images for quantitative evaluation. With its contactless nature and advantages in speed and automation, the acoustofluidic rotational tweezing system has the potential to be a valuable asset for developmental biology and pre-clinical drug development in pharmacology. Supported by ORIP (R43OD024963), NCI, and NIGMS.
Evaluating a New Class of AKT/mTOR Activators for HIV Latency-Reversing Activity Ex Vivo and In Vivo
Gramatica et al., Journal of Virology. 2021.
https://doi.org/10.1128/JVI.02393-20
Activation of latent HIV-1 expression could benefit many HIV cure strategies. Researchers evaluated two AKT/mTOR activators, SB-216763 and tideglusib, as a potential new class of LRAs. The drugs reactivated latent HIV-1 present in blood samples from aviremic individuals on antiretroviral therapy without causing T cell activation or impaired effector function of cytotoxic T lymphocytes or NK cells. When tested in vivo in monkeys, tideglusib showed unfavorable pharmacodynamic properties and did not reverse SIV latency. The discordance between the ex vivo and in vivo results underscores the importance of developing novel LRAs that allow systemic drug delivery to relevant anatomical compartments. Supported by ORIP (P51OD011092), NIAID, NIGMS, NIMH, and NCI.
Antibody-Mediated Depletion of Viral Reservoirs is Limited in SIV-Infected Macaques Treated Early With Antiretroviral Therapy
Swanstrom et al., Journal of Clinical Investigation. 2021.
https://doi.org/10.1172/JCI142421
Virus-specific strategies to target the latent HIV reservoir in individuals on combination antiretroviral therapy (cART) have been limited by inefficient induction of viral protein expression. Researchers used rhesus macaques to investigate an antibody-mediated reservoir targeting strategy, targeting the CD4 molecule rather than a viral protein, to deplete potential viral target cells irrespective of infection status. Despite profound CD4+ T cell depletion in blood and lymph nodes, time to viral rebound following cART cessation was not delayed in anti-CD4 treated animals compared with controls, likely due to the limited antibody-mediated cell depletion that occurred in rectal tissue and lymphoid follicles. Supported by ORIP (R24OD010976), NCI, and NIAID.
Induction and Characterization of Pancreatic Cancer in a Transgenic Pig Model
Boas et al., PLOS One. 2020.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239391
Preclinical testing of new therapies for pancreatic cancer has been challenging due to lack of a suitable large animal model. Pigs, however, have similar physiology and immune response to humans. Boas et al report the development of a porcine model for pancreatic cancer. H&E and immunohistochemical stains revealed undifferentiated carcinomas, like those of human pancreatobiliary systems. In several pigs, angiographies revealed that the artery supplying the pancreatic tumor could be catheterized using a 2.4 F microcatheter. In summary, pancreatic cancer can be induced in a transgenic pig, and intra-arterial procedures using catheters designed for human interventions were feasible in this model. Supported by ORIP (U42OD011140) and NCI.