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2024-2025 Grant2024-2025 Grant period is now OPEN!
Pre-Proposals are due on May 31st, by 11:59 pm (EST) Click here for the pre-proposal form When invited, full proposals are due August 15th, 2023 by 11:59 pm (EST)
Applicants with pre-proposals that have been selected for the full proposal round will have received an email with instructions.
For funding period 2023-24, CAAT granted two grants.
- Laura Calvillo PhD, Istituto Auxologico Italiano IRCCS, Italy
Title: The use of an advanced model of in-vitro hypertension to test therapeutic properties of imidazo-pyrazolil Ureas in human endothelial cells under flow condition, without the use of animals.
- Mathieu Vinken, University of Brussel
Title: An animal-free approach for human safety testing of food additives
Laura Calvillo, PhD, Hypertension is an important risk factor for cardiovascular morbidity/mortality. The main contributors to this condition are blood pressure mechanical increase (i.e. shear-stress) and biochemical up-regulation by the hormone angiotensin II (ANG II). The possibility to discriminate among their mechanisms of action may allow to test new therapies and improve the evaluation of their efficacy. To this aim, animal models are too complex and classic in vitro cell cultures too simple. Therefore, advanced in vitro tools able to better reproduce physiopathological conditions are needed. In this project, IVTech® Bioreactors-LivePa System simulating both the blood flow and the mechanical increase of blood pressure, will be used to provide an advanced model of hypertension, which might fill the gap between in vivo and in vitro studies. Alan and Helen Goldberg In-Vitro Toxicology Grant will be employed to stimulate endothelial cells with LivePa and/or ANG II to mimic the two components of hypertensive stimuli, in the absence or presence of an anti-hypertensive/inflammatory molecule specifically purified for this study. Cell activation pathways and hypertension-/inflammation-associated factors released by the cells in the different experimental conditions will be evaluated by suitable techniques. These findings will shed light on still unknown aspects of the interaction between hypertension and immunity, offering a better chance to transfer the laboratory results to the clinic. Moreover, the possibility to test new molecules (e.g. the proposed one) represents a new tool for future therapeutic approaches. Mathieu Vinken, Several concerns have been raised in recent years regarding the safety of food additives. Among those are a number of colorants, sweeteners, anti-caking or glazing agents that have been shown to cause adverse effects in the liver of laboratory animals. The present project elucidates the mechanisms underlying these presumed hepatotoxic effects by incubating these food additives in tridimensional spheroid cultures of primary human hepatocytes and non-parenchymal liver cells. Through whole transcriptome templated oligo assay with sequencing read-out analysis and pathway analysis, a mechanistic scenario of the hepatotoxic effects induced by the food additives is established. This is substantiated by a series of translational and functional analyses of known triggers and key events in liver toxicity, in particular steatotic and cholestatic insults. Furthermore, the use of effects at the transcriptional level for setting limits for safe daily intake of food additives is explored. Overall, the outcome of the present project sheds more light onto the hepatotoxic potential of food additives and demonstrates the power of human-based in vitro experimentation for chemical risk assessment purposes.
General Award Information:The grants program (http://caat.jhsph.edu/programs/grants) is a centerpiece of our work, providing initial funding for scientists to develop alternatives to the use of animals in biomedical research and product safety testing. To date, the center has funded over 300 grants (including renewals) for a total of more than $6 million. The Johns Hopkins Center for Alternatives to Animal Testing (CAAT) is soliciting projects that focus on the implementation of the NAS Report: Toxicity Testing in the 21st Century: A Vision and a Strategy in the following areas: - Proposals Relating to Toxicology: Maximum grant amount is $40,000. The objective should be to significantly reduce or replace laboratory animals. Examples of acceptable projects could include: providing mechanistic understanding of in vitro responses to toxicants in human cells, development of AOPs, or conducting systematic reviews. Consideration should be given to the translation of this new method to evaluate/predict health outcomes.
- Proposals relating to Refinement are awarded through a different funding mechanism: See Science-Based Refinement Awards – funded separately.
Although relatively small individually, these grants offer critical seed money that allows researchers to demonstrate the value of a particular area of study so they can gain support from the NIH and other sources. We have a stringent, peer-reviewed process for selecting the recipients of these grants. This process consists of sending each application to at least two to three experts in the field from academic, industrial, and government institutions. These reviewers evaluate the applications with regard to scientific merit, budget appropriateness, suitability to CAAT's mission, and expertise of the investigators. They also assign a priority score based on the scoring system used by the NIH. At the CAAT annual advisory board meeting, these applications are reviewed by board members. Board members constitute the voting contingent for the grant applications and assign priority scores in a secret ballot format based upon a synopsis of the outside reviews and the board reviewers. The applications are then ranked in order of priority score and those that receive fundable scores are awarded funds based upon availability of money for the fiscal year. We continue to monitor the long-term progress of the Research Grant Program by requiring our grant recipients to submit copies of publications resulting from the work supported by CAAT grant funds. We maintain a list of publications and an archive of journal reprints. Grants Program Coordinator: Fenna Sillé (fsille1@jhu.edu) | 
