Bio

Bio


Prior to a career in medicine, Dr. Chang was an English major and subsequent novelist at night. During the days, he taught literature part-time at Rutgers University, and for extra money, worked in a laboratory in NYC washing test tubes. Inspired by his laboratory mentor, he began volunteering at the hospital next door, and developed a love for interacting with patients. Through this experience, he saw how caring for others could form deep bonds between people - even strangers - and connect us in a way that brings grandeur to ordinary life.

In addition to seeing patients, Dr. Chang is a physician-scientist devoted to advancing the field of cardiovascular medicine. His research has been focused on identifying a new genetic organism that better models human heart disease than the mouse. For this purpose, he has been studying the mouse lemur, the smallest non-human primate, performing cardiovascular phenotyping (vital signs, ECG, echocardiogram) on lemurs both in-bred (in France) and in the wild (in Madagascar) to try to identify mutant cardiac traits that may be heritable - and in the process, characterize the first high-throughput primate model of human cardiac disease.

Clinical Focus


  • Cardiology
  • Preventive Cardiology
  • Internal Medicine

Academic Appointments


Honors & Awards


  • Advanced Residency Training at Stanford (ARTS) Program, Stanford University School of Medicine (6/2016 - current)
  • ASCI-AAP Travel Grant Award, American Society for Clinical Investigation, Association of American Physicians (2011)
  • Member, Gold Humanism Honor Society (2008 - current)
  • HHMI Medical Research Fellowship, Howard Hughes Medical Institute, National Institutes of Health (2006-2007)
  • NHLBI/NIH Summer Research Fellowship, National Institutes of Health (2005)

Professional Education


  • Board Certification: Internal Medicine, American Board of Internal Medicine (2018)
  • Residency:University of Minnesota Internal Medicine Residency (2014) MN
  • Fellowship:Stanford University Cardiovascular Medicine Fellowship (2017) CA
  • Medical Education:University of Cincinnati College of Medicine Registrar (2009) OH

Publications

All Publications


  • Molecular profiling of dilated cardiomyopathy that progresses to heart failure. JCI insight Burke, M. A., Chang, S., Wakimoto, H., Gorham, J. M., Conner, D. A., Christodoulou, D. C., Parfenov, M. G., Depalma, S. R., Eminaga, S., Konno, T., Seidman, J. G., Seidman, C. E. 2016; 1 (6)

    Abstract

    Dilated cardiomyopathy (DCM) is defined by progressive functional and structural changes. We performed RNA-seq at different stages of disease to define molecular signaling in the progression from pre-DCM hearts to DCM and overt heart failure (HF) using a genetic model of DCM (phospholamban missense mutation, PLN(R9C/+)). Pre-DCM hearts were phenotypically normal yet displayed proliferation of nonmyocytes (59% relative increase vs. WT, P = 8 × 10(-4)) and activation of proinflammatory signaling with notable cardiomyocyte-specific induction of a subset of profibrotic cytokines including TGFβ2 and TGFβ3. These changes progressed through DCM and HF, resulting in substantial fibrosis (17.6% of left ventricle [LV] vs. WT, P = 6 × 10(-33)). Cardiomyocytes displayed a marked shift in metabolic gene transcription: downregulation of aerobic respiration and subsequent upregulation of glucose utilization, changes coincident with attenuated expression of PPARα and PPARγ coactivators -1α (PGC1α) and -1β, and increased expression of the metabolic regulator T-box transcription factor 15 (Tbx15). Comparing DCM transcriptional profiles with those in hypertrophic cardiomyopathy (HCM) revealed similar and distinct molecular mechanisms. Our data suggest that cardiomyocyte-specific cytokine expression, early fibroblast activation, and the shift in metabolic gene expression are hallmarks of cardiomyopathy progression. Notably, key components of these profibrotic and metabolic networks were disease specific and distinguish DCM from HCM.

    View details for PubMedID 27239561

    View details for PubMedCentralID PMC4882118

  • 5 ' RNA-Seq identifies Fhl1 as a genetic modifier in cardiomyopathy JOURNAL OF CLINICAL INVESTIGATION Christodoulou, D. C., Wakimoto, H., Onoue, K., Eminaga, S., Gorham, J. M., Depalma, S. R., Herman, D. S., Teekakirikul, P., Conner, D. A., McKean, D. M., Domenighetti, A. A., Aboukhalil, A., Chang, S., Srivastava, G., McDonough, B., De Jager, P. L., Chen, J., Bulyk, M. L., Muehlschlege, J. D., Seidman, C. E., Seidman, J. G. 2014; 124 (3): 1364-1370

    Abstract

    The transcriptome is subject to multiple changes during pathogenesis, including the use of alternate 5' start-sites that can affect transcription levels and output. Current RNA sequencing techniques can assess mRNA levels, but do not robustly detect changes in 5' start-site use. Here, we developed a transcriptome sequencing strategy that detects genome-wide changes in start-site usage (5'RNA-Seq) and applied this methodology to identify regulatory events that occur in hypertrophic cardiomyopathy (HCM). Compared with transcripts from WT mice, 92 genes had altered start-site usage in a mouse model of HCM, including four-and-a-half LIM domains protein 1 (Fhl1). HCM-induced altered transcriptional regulation of Fhl1 resulted in robust myocyte expression of a distinct protein isoform, a response that was conserved in humans with genetic or acquired cardiomyopathies. Genetic ablation of Fhl1 in HCM mice was deleterious, which suggests that Fhl1 transcriptional changes provide salutary effects on stressed myocytes in this disease. Because Fhl1 is a chromosome X-encoded gene, stress-induced changes in its transcription may contribute to gender differences in the clinical severity of HCM. Our findings indicate that 5'RNA-Seq has the potential to identify genome-wide changes in 5' start-site usage that are associated with pathogenic phenotypes.

    View details for DOI 10.1172/JCI70108

    View details for Web of Science ID 000332347700050

    View details for PubMedID 24509080

    View details for PubMedCentralID PMC3934171

  • Connexin43 Modulates Cell Polarity and Directional Cell Migration by Regulating Microtubule Dynamics PLOS ONE Francis, R., Xu, X., Park, H., Wei, C., Chang, S., Chatterjee, B., Lo, C. 2011; 6 (10)

    Abstract

    Knockout mice deficient in the gap junction gene connexin43 exhibit developmental anomalies associated with abnormal neural crest, primordial germ cell, and proepicardial cell migration. These migration defects are due to a loss of directional cell movement, and are associated with abnormal actin stress fiber organization and a loss of polarized cell morphology. To elucidate the mechanism by which Cx43 regulates cell polarity, we used a wound closure assays with mouse embryonic fibroblasts (MEFs) to examine polarized cell morphology and directional cell movement. Studies using embryonic fibroblasts from Cx43 knockout (Cx43KO) mice showed Cx43 deficiency caused cell polarity defects as characterized by a failure of the Golgi apparatus and the microtubule organizing center to reorient with the direction of wound closure. Actin stress fibers at the wound edge also failed to appropriately align, and stabilized microtubule (Glu-tubulin) levels were markedly reduced. Forced expression of Cx43 with deletion of its tubulin-binding domain (Cx43dT) in both wildtype MEFs and neural crest cell explants recapitulated the cell migration defects seen in Cx43KO cells. However, forced expression of Cx43 with point mutation causing gap junction channel closure had no effect on cell motility. TIRF imaging revealed increased microtubule instability in Cx43KO cells, and microtubule targeting of membrane localized Cx43 was reduced with expression of Cx43dT construct in wildtype cells. Together, these findings suggest the essential role of Cx43 gap junctions in development is mediated by regulation of the tubulin cytoskeleton and cell polarity by Cx43 via a nonchannel function.

    View details for DOI 10.1371/journal.pone.0026379

    View details for Web of Science ID 000295981600056

    View details for PubMedID 22022608

    View details for PubMedCentralID PMC3194834

  • Genetics of hypertrophic cardiomyopathy CURRENT OPINION IN CARDIOLOGY Konno, T., Chang, S., Seidman, J. G., Seidman, C. E. 2010; 25 (3): 205-209

    Abstract

    Hypertrophic cardiomyopathy (HCM), the most common inherited cardiac disorder, exhibits remarkable genetic and clinical heterogeneity. This manuscript reviews recent discoveries of disease-causing genes and their clinical consequences, and provides an overview of research that aims to elucidate how HCM ensues from a single-nucleotide mutation.The spectrum of genes that are mutated in HCM has expanded. In combination with newly developed sequencing technologies, there are now robust strategies for gene-based diagnosis in HCM. Understanding the molecular pathophysiology of HCM has emerged from the study of genetically engineered animal models of disease, and new data indicate important roles for altered intracellular Ca²⁺ regulation and oxidative stress. Pharmacologic strategies to normalize these processes show promise in attenuating HCM in experimental models.The current repertoire of HCM genes allows effective gene-based diagnosis, information that enables accurate assessment of disease risk in family members, and provides some insight into clinical course. From mechanistic insights gleaned from fundamental investigations of experimental HCM models, novel therapeutic targets that may provide new benefits for HCM patients have surfaced.

    View details for DOI 10.1097/HCO.0b013e3283375698

    View details for Web of Science ID 000276879500006

    View details for PubMedID 20124998

    View details for PubMedCentralID PMC2932754