I am Head of the Skeletal Dysplasia Laboratory at Nemours Children’s Health, DE (NCH-D), Professor of
Pediatrics at Thomas Jefferson University, Professor at the University of Delaware, and Adjunct Professor at Medical School, Shimane University and Gifu University, Japan. I have authored and co-authored over 280 peer-reviewed publications since 1997 (h-index; 58 in Scopus; 70 in Google Scholar) with over 10 articles annually, and over 80% of them originated from our lab. Twelve patents were issued, and four were filed. My research field and expertise have been in inherited metabolic disorders and genetic diseases, especially mucopolysaccharidoses (MPS), a group of lysosomal storage disorders, for over 40 years. I have contributed to gene cloning, identification of gene mutations, phenotype/genotype correlation, protein structure biology, clinical diagnosis, diagnosis and therapy development, patient registry, natural history program, newborn screening, proteomics, identification of biomarkers, and clinical trials in the MPS field; hematopoietic stem cell transplantation (HSCT), enzyme replacement therapy (ERT), gene therapy, and substrate reduction therapy (SRT). I contributed to developing and publishing various therapeutic approaches by targeting ERT, HSCT, SRT, and gene therapies (AAV, CRISPR Cas9, and lentiviral vectors) on MPS mouse models and established glycosaminoglycans assay system by ELISA and LC-MS/MS. As a PI or co-investigator, I have been awarded many NIH grants. Currently, I am conducting 1R01HD102545-01A1; Non-invasive functional assessment and pathogenesis of Morquio A (PI), 1R01HD104814-01A1; Enhancement of Newborn Screening Diagnostic
Paradigms to Improve the Efficacy of Treatment for Krabbe Disease, Pompe Disease, and
Mucopolysaccharidosis Type 1 (site PI), FNIH RFP NUMBER: 2022-BGTC-005; AAV Gene Therapy for Mucopolysaccharidosis IVA Protocol NEM101 (Co-PI), 1R43HD114328-01; Safety, pharmacokinetics, and efficacy studies of RTB:GALNS product in Morquio A mouse model (site-PI), 1R43AR084638-01; Cell-based Gene Therapy for MPS IVA (site-PI). Furthermore, we have published around 190 manuscripts related to Morquio A since 1991. Major studies on Morquio A have been performed by our group and collaborators for the past 35 years involving both basic and clinical research: 1) cloning of human GALNS gene, 2) identification of over 170 mutations, 3) tertiary structure of GALNS and purification of recombinant human GALNS, 4) establishment of five different murine models, 5) KS assay by ELISA and tandem mass spectrometry, 6) educational CD, 7) International Morquio Registry, 8) ERT on a mouse model, 9) development of growth chart, 10) assessment of
therapeutic efficacy by targeting ERT, gene therapies including AAV, HSCT, SRT on Morquio A mouse models, 11) Biannual Morquio Conference since 2011, and 12) establishment of GAG assay system by ELISA and LC-MS/MS.
According to these activities, at Nemours Children’s Hospital, Delaware, we have over 120 patients with Morquio A under our multidisciplinary team despite a rare disorder and have over 100 related publications in the past 10 years as a leading institute worldwide. The “holistic” natural history study to elucidate the disease was conducted, including those that evaluated blood KS values, height (bone growth) and establishment of growth chart, pulmonary function, gait analysis, bone mineral density, skeletal images (X-rays, CT, MRI for trachea and skeletal), activity of daily living questionnaire, and finger laxity. Thus, we already have a broad international network among patients, their families, Morquio A society, physicians, and local communities to conduct Morquio A natural history program and successive clinical trials.
Our current research laboratory, consisting of 18 members, is a testament to my dedication to mentorship. I have trained 20 postdoctoral fellows and 48 students (20 Ph.D. students, 6 master students, 11 undergraduates, 11 medical students) in Japan and the USA. Their current positions, including 7 full professors, 3 associate professors, 2 assistant professors, and 4 Presidents of the clinics/hospitals, demonstrate the impact of my mentoring skills and experience.
I have assembled a group of outstanding co-investigators and collaborators with strong expertise and track records to accomplish the proposed research. Brian Bigger, PhD at the University of Edinburgh, a cell biologist with expertise in LV-HSC GT with more than 110 publications; Khan, PhD is a molecular biologist with expertise in liquid chromatography-tandem mass spectrometry (LC-MS/MS) and biomarkers; and Hossain, PhD, a statistician with experience in methodological innovation and exploring etiologic pathways and health trends in diverse pediatric populations that include tracking changes in health trajectories over time. We will get strong support from the HSCT and MSC expert (Taketani MD, PhD). PuREC Co. Ltd. (Takahashi, CEO) kindly provides highly purified human MSCs (REC) and its knowledge, and Morquio communities strongly support this project (see letters of support). This team has worked together efficiently to generate compelling preliminary data and will continue to ensure the progress of the proposed research.
In summary, I have a demonstrated record of successful and productive research projects in my career, and my expertise and experience have prepared me to lead the proposed project of NIH grant as a PI.