Professor, Pharmacology and Internal Medicine
Phone: 501-526-5397
Email: hchang@uams.edu
Education
M.D.: National Taiwan University
MPH: Harvard Chan School of Public Health
M.S.: Harvard Chan School of Public Health
Clinical Internship: George Washington University Medical Center
Residency: Boston University Medical Center
Clinical Fellowship: Harvard Medical School, Boston Children’s Hospital
Research Fellowship: Harvard Medical School, Boston Children’s Hospital
Research Interests
As a cross-discipline physician scientist, my current research interest is clinical trials on onco-cardiology (cardio-oncology). Doxorubicin, an inhibitor of DNA topoisomerase 2a (Top2a), is routinely used in the treatment of breast cancer, sarcoma, and pediatric leukemia. Of the two topoisomerase 2 isozymes, Top2a is highly expressed in cancer cells and is required for cell division. However, adult cardiomyocytes express only topoisomerase 2b (Top2b), which is involved in DNA transcription, but not DNA replication. Long-term cancer survivors who were treated with doxorubicin and other anthracyclines often suffer from dose-dependent cardiotoxicity. Our laboratory data showed that Top2a mediates doxorubicin’s tumoricidal activity, whereas Top2b mediates doxorubicin’s cardiotoxic effect. Early administration of dexrazoxane provides the window of opportunity to prevent doxorubicin induced heart failure. I translated these bench results from our animal studies to clinical trials. This NIH-funded project titled “Prevention of Heart Failure induced by Doxorubicin with Early Administration of Dexrazoxane” will test a novel hypothesis to prevent cardiotoxicity of doxorubicin.
Recent Research Support
- RO1 HL151993, Chang (PI), 6/15/2020-5/31/2025
NIH/NHLBI & NCI
Title: “Prevention of Heart Failure induced by Doxorubicin with early administration of Dexrazoxane”
The goal of this project is to conduct clinical trials testing the hypothesis that early administration of dexrazoxane will prevent doxorubicin-induced cardiotoxicity.
Clinical trial name: Phoenix - RO1 HL126916 NIH, Chang (Co-PI), 4/1/2015-8/31/2021
NIH/NHLBI
Title: “Doxorubicin-induced Cardiotoxicity: Role of Topoisomerase 2b”
The goal of this project is to determine whether degrading Topoisomerase 2b with dexrazoxane can prevent doxorubicin-induced cardiotoxicity in mice.
Recent and Selected Publications
- Yang FM, Chang HM, Yeh ETH: Regulation of TLR4 signaling through theTRAF6/sNASP axis by reversible phosphorylation mediated by CK2 and PP4 Proc Natl Acad Sci USA 2021 Nov. 23;118 (47): e2107044118;doi:10,1073/pnas.2107044118 PMID: 34789577
- Sheng ZF, Zhang H, Zheng P, Chen S, Gu Z, Zhou JJ, Phaup JG, Chang HM, Yeh ETH, Pan HL, Li DP: Impaired Kv7 channel activity in the central amygdala contributes to elevated sympathetic outflow in hypertension. Cardiovasc Res. 2021 Jan 29:cvab031. doi: 10.1093/cvr/cvab031. Online ahead of print. PMID: 33512443
- Chang HM, Yeh ET, SUMO: From Bench to Bedside. Physiological Reviews. 2020, Oct.1;100(4):1599-1619. Doi:10,1152/physrev.0002.2019 PMID:32666886
- Li J, Chang HM, Banchs J, Araujo D, Hassan SA, Wagar EA, Yeh ET, Meng Q. Detection of subclinical cardiotoxicity in sarcoma patients receiving continuous doxorubicin infusion or pre-treatment with dexrazoxane before bolus doxorubicin. Cardio-Oncology, 2020 Jan 2;6:1 doi:10.1186/s40959-019-0056-3 ecollection 2020 PMID:32154027
- Yeh ETH, Ewer MS, Moslehi J, Dlugosz-Danecka M, Banchs J, Chang HM, Minotti G Mechanisms and Clinical Course of Cardiovascular Toxicity of Cancer Treatment I. Oncology. Semin Oncol 2019 Dec 46(6):397-402 doi:10.1053/j.seminoncol 2019.10.006 Epub 2019 Nov 11 PMID: 31753424
- Yang FM, Zuo Y, Zhou W, Xia C, Hahm B, Sullivan M, Cheng J, Chang HM, Yeh ET sNASP Inhibits TLR Signaling to Regulate Immune Response in Sepsis. J Clin Invest. 2018 Jun 1;128(6):2459-2472. doi: 10.1172/JCI95720. Epub 2018 May 7. PMID: 29733298
- Chang HM, Okwuosa T, Scarabelli T, Moudgil R, Yeh ET Cardiovascular Complications of Cancer Therapy: Best Practices in Diagnosis, Prevention, and Management: Part 2, J Am Coll Cardiol 2017 November 14;70 (20):2552-2565, PMID: 29145955
- Chang HM, Moudgil R, Scarabelli T, Okwuosa T, Yeh ET Cardiovascular Complications of Cancer Therapy: Best Practices in Diagnosis, Prevention, and Management: Part 1, J Am Coll Cardiol 2017 November 14;70(20):2536-2551, PMID: 29145954
- Yeh ET, Chang HM Cancer and Clot: Between a Rock and a Hard Place, J Am Coll Cardiol 2017 August 22; 70 (8): 939-941 PMID: 28818203
- Yeh ET, Chang HM Oncocardiology-Past, Present, and Future: A Review, JAMA Cardiol. 2016 Dec 1;1(9):1066-1072 PMID: 27541948
- Chang HM. Cancer Pain Management. Medical Clinics of North America,1999 May Vol. 83, No 3:711-736 PMID: 10386122
- Okura T, Gong L, Kamitani T, Wada T, Okura I, Wei CF, Chang HM, Yeh ETH. Protection against Fas/APO-1 and tumor necrosis factor-mediated cell death by a novel protein, Sentrin. Journal of Immunology. 1996 Cutting Edge, 157:4277-4281, PMID: 8906799
- Ferrante FM, Bedder M, Caplan RA, Chang HM, Connis RT, Harrison P, Jamison RN, Krane EJ, Nedelikovic S, Patt R., Portenoy RK. Practice Guidelines for Cancer Pain Management. Developed by Task Force on Pain Management, Cancer Pain Section. American Society of Anesthesiologists Anesthesiology, 1996; 84: 1243-57
- Yeh ET, Kamitani T, Chang HM. Biosynthesis and processing of the glycosylphosphatidylionsitol anchor in mammalian cells. Seminars in Immunology, 1994 6:73-80, PMID:8054538
- Kamitani T, Chang HM, Rollins C, Waneck GL, Yeh ETH. Correction of the class H defect in glycosylphosphatidylinositol anchor biosynthesis in Ltk- cells by a human cDNA clone. Journal of Biological Chemistry, 1993 268: 20733-20736, PMID: 8407896
- DeGasperi R, Thomas LJ, Sugiyama E, Chang HM, Beck PJ, Orlean P, Albright C, Waneck G, Sambrook J, Warren CD, and Yeh ETH. Correction of a defect in mammalian GPI anchor biosynthesis by a transfected yeast gene. Science, 1990 250:988-991, PMID: 1978413
- Chang HM, Berde CB, Holz GG, Steward GF, Kream RM. Sufentanil, morphine, met-enkephalin and k-agonist (U50,488H) inhibit substance P release from primary sensory neurons: a model for presynaptic spinal opioid actions. Anesthesiology. 1989; 70:672-677 PMID: 2467589