In a recent study in the Proceedings of the National Academy of Sciences, TIME Lab researchers collaborated with cancer experts from Harvard Medical School and tuberculosis (TB) experts from the National Institues of Health to explore and exploit the similarities between malignant tumors and TB granulomas. We have found that both diseases share a propensity of matrix molecule deposition (e.g., collagen and hyaluronic acid) and abnormal and compressed (i.e., non-perfused) blood vessels. We used the rabbit model of TB, which recapitulates human disease, to test host-directed therapies (HDTs) that reprogram these abnormal blood vessels and matrix in granulomas. These HDTs are repurposed FDA-approved agents originally studied in cancer for their vascular normalizing (bevacizumab) and matrix-targeting (losartan) effects. We found that these HDTs were able to normalize blood vessels and extracellular matrix, improve delivery of anti-bacterial agents, and reduce bacteria numbers in TB granulomas. Strikingly, the HDTs alone (without anti-bacterial agents) were able to reduce bacterial loads. Finally, to identify the mechanisms underlying this surprising benefit, we collected granuloma and lung tissues and performed RNA-sequencing combined with bioinformatics approaches. We found that the HDTs promoted inflammatory responses against the TB bacteria, both in immune and non-immune cells in the lung. Because bevacizumab and losartan are approved, safe, and affordable (either in original or biosimilar formulations), our preclinical study lays the groundwork for direct clinical translation to test these HDTs in TB patients for their ability to improve outcomes of anti-bacterial therapy. Read more about this study in a press release by Notre Dame News.