Research
CYP1 inhibition protects against anthracycline-induced cardiac toxicity
We identified a potent small molecule that protects against doxorubicin-induced heart dysfunction in zebrafish and mice. Using chemical and genetic approaches, we found that inhibition of cytochrome P450 family 1 enzymes is critical to the protective activity of these compounds.
- Inhibition of Cyp1a Protects Mice against Anthracycline Cardiomyopathy
- Liu J, Curtin C, Lall R, Lane S, Wieke J, Ariza A, Sejour L, Vlachos I, Zordoky BN, Peterson RT, Asnani A.
- bioRxiv (preprint).
- Cyp1 Inhibition Prevents Doxorubicin-Induced Cardiomyopathy in a Zebrafish Heart-Failure Model
- Lam PY, Kutchukian P, Anand R, Imbriglio J, Andrews C, Padilla H, Vohra A, Lane S, Parker DL Jr, Cornella Taracido I, Johns DG, Beerens M, MacRae C, Caldwell JP, Sorota S, Asnani A, Peterson RT.
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ChemBioChem 2020 Jul 1;21(13):1905-1910.
- Highly Potent Visnagin Derivatives Inhibit Cyp1 and Prevent Doxorubicin Cardiotoxicity
- Asnani A, Zheng B, Liu Y, Wang Y, Chen HH, Vohra A, Chi A, Cornella Taracido I, Wang H, Johns DG, Sosnovik DE, Peterson RT.
- JCI Insight 2018 Jan 11;3(1):e96753.
- Visnagin Protects Against Doxorubicin-Induced Cardiomyopathy Through Modulation of Mitochondrial Malate Dehydrogenase
- Liu Y, Asnani A, Zou L, Bentley VL, Yu M, Wang Y, Dellaire G, Sarkar KS, Dai M, Chen HH, Sosnovik DE, Shin JT, Haber DA, Berman JN, Chao W, Peterson RT.
- Science Translational Medicine 2014 Dec 10;6(266):266ra170.
Heme signaling and immune mechanisms in cardiomyopathy
We found that changes in the heme-binding protein hemopexin were associated with early cardiac toxicity in patients and in mice treated with anthracyclines. In mice, hemopexin protects against cardiac toxicity by modulating the monocyte/macrophage response and cardiac ferroptosis. In collaboration with the Kim lab, we defined the role of hemopexin and associated pathways in sickle cell cardiomyopathy. In collaboration with the Alcaide lab, we identified a role for cytotoxic T cells in doxorubicin-induced cardiac dysfunction.
- Cytotoxic T cells drive doxorubicin-induced cardiac fibrosis and systolic dysfunction
- Bayer AL, Zambrano MA, Smolgovsky S, Robbe ZL, Ariza A, Kaur K, Sawden M, Avery A, London C, Asnani A, Alcaide P.
- Nature Cardiovascular Research 2024;3:970-986.
- Excess heme upregulates heme oxygenase 1 and promotes cardiac ferroptosis in mice with sickle cell disease
- Menon AV, Liu J, Tsai HP, Zeng L, Yang S, Asnani A, Kim J.
- Blood 2022 Feb 10; 139(6):936-941.
- Circulating hemopexin modulates anthracycline cardiac toxicity in patients and in mice
- Liu J, Lane S, Lall R, Russo R, Farrell L, Coskun MD, Curtin C, Araujo-Gutierrez R, Scherrer-Crosbie M, Trachtenberg BH, Kim J, Tolosano E, Ghigo A, Gerszten RE, Asnani A.
- Science Advances 2022 Dec 23;8(51):eadc9245.
Improving cardiac risk stratification in patients receiving anthracyclines
Our work has identified new clinical, blood, and ECG biomarkers associated with the development of early cardiac dysfunction and heart failure in patients treated with anthracyclines.
- Cardiotoxicity of combined pegylated liposomal doxorubicin and bevacizumab therapy: a propensity-matched cohort study and disproportionality analysis
- Hoeger CW, Choudhary A, Diaz ANR, Pinto T, Smalec S, Doladille C, Wadhera R, Shea M, Khadke S, Salem JE, Ganatra S, Asnani A.
- Cardiooncology. 2025 Jul 2;11(1):59.
- Cancer therapy-associated cardiotoxicity: A look at frailty
- Hanlon E, Rosas Diaz AN, Sedrak M, Strom JB, Asnani A.
- Journal of Geriatric Oncology 2024 Jul 23:101835.
- Sex Differences in the Development of Anthracycline-Associated Heart Failure
- Rosas Diaz AN, Pajares Hurtado G, Ariza Manzano AA, Keyes MJ, Turissini C, Choudhary A, Curtin C, Dommaraju S, Warack S, Strom JB, Asnani A.
- Journal of Cardiac Failure 2023.
- The Spatial Ventricular Gradient is an Independent Predictor of Anthracycline-Associated Cardiotoxicity.
- Rosas Diaz AN, Stabenau HF, Hurtado GP, Warack S, Waks JW, Asnani A.
- JACC: Advances 2023 March 1; 2(2):100269
- Changes in Citric Acid Cycle and Nucleoside Metabolism Are Associated with Anthracycline Cardiotoxicity in Patients with Breast Cancer
- Asnani A, Shi X, Farrell L, Lall R, Sebag IA, Plana JC, Gerszten RE, Scherrer-Crosbie M.
- J Card Trans Res 2020;13:349-356.