Professor, Pharmacology and Internal Medicine
Phone: 501-526-5397
Email: hchang@uams.edu
Education
MD: National Taiwan University
MPH: Harvard Chan School of Public Health
MS: 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
I am a cross-discipline physician scientist. My current research interest is to conduct 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” is testing a novel hypothesis to prevent cardiotoxicity of doxorubicin.
Previously, I contributed to the cloning of a ubiquitin-like protein called Sentrin, which was eventually renamed to SUMO (Small ubiquitin-like modifiers). This discovery led to the development of a new post-translational protein modification pathway that is involved in every aspect of cell biology and human physiology.
My early contribution to science was to demonstrate the effects of opioid mu and kappa agonists on Substance P release using primary sensory neuron culture from dorsal root ganglia. This work led to a grant from Searle Company to study the effects of Misoprostol and NSAIDs on Substance P release from primary sensory neurons. My work contributed to the understanding of pain mechanism at the neurochemical level.
In addition, I am a former member of the Task Force on Pain Management Clinical Practice Guidelines, Cancer Pain Section for American Society of Anesthesiologists. Applying principles of evidence-based medicine, ten task force members and I developed clinical practice guidelines on cancer pain management. This was the first set of national clinical practice guidelines on cancer pain management by the American Society of Anesthesiologists. I served on the scientific advisory committee of the university clinical research center at the University of Texas Health Science Center at Houston and M.D. Anderson Cancer Center for ten years. I also served as a director on the Board of The American Academy of Pain Medicine and advocated for education in pain medicine and evidence-based medicine. Currently I am serving on the Scientific Review and Guidelines Committee. I was a faculty member at the Massachusetts General Hospital, Harvard Medical School, the University of Texas at Houston, the University of Texas M.D. Anderson Cancer Center, and the University of Missouri prior to joining the University of Arkansas for Medical Sciences.
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
Recent and Selected Publications
Sheng ZF, Zhang H, Phaup JG, Zheng P, Kang XL, Liu Z, Chang HM, Yeh ET, Johnson AK, Pan HL, Li DP. Corticotropin=releasing hormone neurons in the central nucleus of amygdala are required for chronic stress-induced hypertension. Cardiovascular Research. 2023 Jul 06;119(8):1751-1762. PMID: 37041718
Wang C, Nistala R, Cao M, Pan Y, Behrens M, Doll D, Hammer RD, Nistala P, Chang HM, Yeh ETH, Kang X. Dipeptidylpepidase 4 promotes survival and stemness of acute myeloid leukemia stem cells. Cell Rep. 2023 Feb 17; 42(2):112105. PMID: 36807138
Zhang H, Sheng ZF, Wang J, Zheng PR, Kang XL, Chang HM, Yeh ET, Li DP. Signaling pathways involved in NMDA-induced suppression of M-channels in corticotropin-releasing hormone neurons in central amygdala. J Neurochem. 2022 June 161(6):478-491, doi: 10.1111/jnc.15647. PMID: 35583089.
Sheng ZF, Zhang H, Zheng P, Chen S, Gu Z, Zhou JJ, Phaup JG, Chang HM, Yeh ET, Pan HL, Li DP: Impaired Kv7 channel activity in the central amygdala contributes to elevated sympathetic outflow in hypertension. Cardiovasc Res. 2022 Jan 29;118(2):585-596. doi: 10.1093/cvr/cvab031. PMID: 33512443 5. Yang FM, Chang HM, Yeh ET. Regulation of TLR4 signaling through the TRAF6/sNASP axis by reversible phosphorylation mediated by CK2 and PP4. Proc Natl Acad Sci U S A. 2021 Nov 23;118(47). doi: 10.1073/pnas.2107044118. PMID: 34789577; PubMed Central PMCID: PMC8617457.
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 7. 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
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