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.
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.
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).
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.
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. ChemBioChem 2020 Jul 1;21(13):1905-1910.
Heme signaling in anthracycline and sickle cell 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.
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.
Rosas Diaz AN, Stabenau HF, Hurtado GP, Warack S, Waks JW, Asnani A. JACC: Advances 2023 March 1; 2(2):100269
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.
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.