Dwi Utami Kemaladewi, PhD

  • Assistant Professor of Pediatrics

Dwi Kemaladewi has extensive training in human genetics and development of genetic therapy, with a focus on neuromuscular disorders. She received her PhD in Human Genetics from Leiden University Medical Center, Netherlands (2007-2012), and completed a postdoctoral training at the Hospital for Sick Children, Toronto, Canada (2012-2019).

She is interested in understanding the molecular mechanisms underlying layers of pathophysiology involved in muscular dystrophies, including muscle atrophy, regeneration, fibrosis, and nerve damage. In parallel, the exposure to technology-driven field of human genetics has provided a strong basis on her translational research arm. She has a robust scientific portfolio on the development and evaluation of therapeutic genetics, such as antisense oligonucleotides and CRISPR/Cas to correct mutations and modulate disease modifier genes in mouse and patient-derived cell models. Her work has resulted in peer-reviewed publications, intellectual properties, early-career funding, as well as valuable supports from rare disease patient communities.

Kemaladewi joined the Department of Pediatrics, University of Pittsburgh School of Medicine in February 2019 as a tenure-track Assistant Professor and Mellon Scholar. Her research lab is embedded within the Division of Genetic and Genomic Medicine and Center for Rare Disease Therapy at UPMC Children’s Hospital of Pittsburgh. She aspires to translate the knowledge acquired throughout her training in neuromuscular disorders to many other rare diseases with unmet therapeutic needs.

Professional and Scientific Society Memberships

  • World Muscle Society, 2012-Present  
  • American Society of Human Genetics, 2015-Present  
  • TREAT-NMD, 2015-Present  
  • American Society for Gene and Cell Therapy, 2019-Present  

Education & Training

  • BSc, Life Sciences, Hogeschool van Arnhem en Nijmegen, 2007
  • PhD, Human Genetics, Leiden University Medical Center, 2012
  • Postdoctoral Fellowship, Hospital for Sick Children, 2012-2017
  • Research Associate, Hospital for Sick Children, 2017-2019

Selected Publications

Kemaladewi DU, Hoogaars WM, van Heiningen SH, Terlouw S, de Gorter DJ, den Dunnen JT, van Ommen GJ, Aartsma-Rus A, ten Dijke P, 't Hoen PA. Dual exon skipping in myostatin and dystrophin for Duchenne muscular dystrophy. BMC Med Genomics. 2011 Apr 20;4:36. doi: 10.1186/1755-8794-4-36. PubMed PMID: 21507246;PubMed Central PMCID: PMC3107769.

Kemaladewi DU, de Gorter DJ, Aartsma-Rus A, van Ommen GJ, ten Dijke P, 't Hoen PA, Hoogaars WM. Cell-type specific regulation of myostatin signaling. FASEB J. 2012 Apr;26(4):1462-72. doi: 10.1096/fj.11-191189. Epub 2011 Dec 27. PubMed PMID: 22202673.

Shi S, Cai J, de Gorter DJ, Sanchez-Duffhues G, Kemaladewi DU, Hoogaars WM, Aartsma-Rus A, 't Hoen PA, ten Dijke P. Antisense-oligonucleotide mediated exon skipping in activin-receptor-like kinase 2: inhibiting the receptor that is overactive in fibrodysplasia ossificans progressiva. PLoS One. 2013 Jul 4;8(7):e69096. doi: 10.1371/journal.pone.0069096. Print 2013. PubMed PMID: 23861958; PubMed Central PMCID: PMC3701692.

Karkampouna S, Kruithof BP, Kloen P, Obdeijn MC, van der Laan AM, Tanke HJ, Kemaladewi DU, Hoogaars WM, 't Hoen PA, Aartsma-Rus A, Clark IM, Ten Dijke P, Goumans MJ, Kruithof-de Julio M. Novel Ex Vivo Culture Method for the Study of Dupuytren's Disease: Effects of TGFβ Type 1 Receptor Modulation by Antisense Oligonucleotides. Mol Ther Nucleic Acids. 2014 Jan 21;3:e142. doi: 10.1038/mtna.2013.69. PubMed PMID: 24448195; PubMed Central PMCID: PMC3912325.

Kemaladewi DU, Pasteuning S, van der Meulen JW, van Heiningen SH, van Ommen GJ, Ten Dijke P, Aartsma-Rus A, 't Hoen PA, Hoogaars WM. Targeting TGF-β Signaling by Antisense Oligonucleotide-mediated Knockdown of TGF-β Type I Receptor. Mol Ther Nucleic Acids. 2014 Apr 1;3:e156. doi: 10.1038/mtna.2014.7. PubMed PMID: 24691207; PubMed Central PMCID: PMC4011125.

Wojtal D*, Kemaladewi DU*, Malam Z, Abdullah S, Wong TW, Hyatt E, Baghestani Z, Pereira S, Stavropoulos J, Mouly V, Mamchaoui K, Muntoni F, Voit T, Gonorazky HD, Dowling JJ, Wilson MD, Mendoza-Londono R, Ivakine EA, Cohn RD. Spell Checking Nature: Versatility of CRISPR/Cas9 for Developing Treatments for Inherited Disorders. Am J Hum Genet. 2016 Jan 7;98(1):90-101. doi: 10.1016/j.ajhg.2015.11.012. Epub 2015 Dec 10. PubMed PMID: 26686765; PubMed Central PMCID: PMC4716669.

Kemaladewi DU, Maino E, Hyatt E, Hou H, Ding M, Place KM, Zhu X, Bassi P, Baghestani Z, Deshwar AG, Merico D, Xiong HY, Frey BJ, Wilson MD, Ivakine EA, Cohn RD. Correction of a splicing defect in a mouse model of congenital muscular dystrophy type 1A using a homology-directed-repair-independent mechanism. Nat Med. 2017 Aug;23(8):984-989. doi: 10.1038/nm.4367. Epub 2017 Jul 17. PubMed PMID: 28714989.

Kemaladewi DU, Benjamin JS, Hyatt E, Ivakine EA, Cohn RD. Increased polyamines as protective disease modifiers in congenital muscular dystrophy. Hum Mol Genet. 2018 Jun 1;27(11):1905-1912. doi: 10.1093/hmg/ddy097. PubMed PMID: 29566247.

Gonorazky HD, Naumenko S, Ramani AK, Nelakuditi V, Mashouri P, Wang P, Kao D, Ohri K, Viththiyapaskaran S, Tarnopolsky MA, Mathews KD, Moore SA, Osorio AN, Villanova D, Kemaladewi DU, Cohn RD, Brudno M, Dowling JJ. Expanding the Boundaries of RNA Sequencing as a Diagnostic Tool for Rare Mendelian Disease. Am J Hum Genet. 2019 Mar 7;104(3):466-483. doi: 10.1016/j.ajhg.2019.01.012. Epub 2019 Feb 28. PubMed PMID: 30827497.

Kemaladewi, DU*, Bassi, PS.*, Erwood, S., Al-Basha, D., Gawlik, KI., Lindsay, K., Hyatt, E., Kember, R., Place, KM., Marks, RM., Durbeej-Hjalt, M., Prescott, S., Ivakine, EA., Cohn, RD. A mutation-independent approach for muscular dystrophy via upregulation of a modifier gene. Nature. 2019 Aug;572(7767):125-130. doi: 10.1038/s41586-019-1430-x. Epub 2019 Jul 24. PubMed PMID: 31341277

Academic and Research Interests

  • Muscular dystrophy
  • Rare diseases
  • Gene therapy
  • Neuromuscular

Research Grants

Therapeutic genetics and disease modeling in LAMA2-CMD, RAC Start-Up, UPMC Children’s Hospital of Pittsburgh, 2021-2023.

Therapeutic genetics and disease modeling in LAMA2-CMD, Cure-CMD, 2020-2022.

Therapeutic genetics and disease modeling in LAMA2-CMD, AFM-Telethon, 2020-2022.

Start-up Fund, Department of Pediatrics:  Interventional genomics in rare diseases, University of Pittsburgh, 2019.

Development Grant:  Interrogation of CRISPR/Cas9-mediated exon inclusion in MDC1A, United States Muscular Dystrophy Association, 2018-2021.

Pilot grant: Teaching an old dog new tricks: Upregulation of disease-modifying gene in DMD, Duchenne Parent Project Netherlands, 2020.

Children’s Trust Young Investigator Award:  Interventional genomics in rare diseases, Children’s Hospital of Pittsburgh Foundation, 2019-2020.

Investigating the role of lipid metabolism in congenital muscular dystrophy, BC Children’s Hospital Canada Rare Disease Foundation, 2019-2020.

Where genetics meet physiology: Disease modifiers in MDC1A skeletal muscle and the peripheral nervous system, The Hospital for Sick Children, 2017-2018.

McLaughlin Centre Accelerator Grant in Genomic Medicine:  Towards identification of comprehensive mutational landscape in Congenital Muscular Dystrophy, University of Toronto, 2017-2018.