Our department is providing advanced medical service for infants, children, adolescents and young adults. The specialties cover most pediatric diseases, including hematology-oncology, immunology, cardiology, neurology, endocrinology, metabolism, nephrology, rheumatology, neonatology, and allergy. On the other hand, our scientific and academic activities encompass a wide spectrum, from basic to clinical research. By focusing on innovative strategies for clarifying pathogenesis, diagnostic tests, and therapeutic interventions, we are looking at comprehensive resolution of the child’s health problems, improving their future.

Our research covers many specialties of pediatric diseases, and the research spans from bench to bedside. Our current main projects are

1. Identification of responsible genes for inborn errors of immunity (IEI).
2. Development of therapeutic approach for IEI
3. Development of innovative techniques for ex vivo cell therapy after hematopoietic stem cell transplantation.
4. Multicenter Registry for pediatric Pulmonary arterial hypertension (PAH) (Congenital Heart Disease related
PAH (JACPHR) and Idiopathic/heritable PAH (JAPHR))
5. Multicenter Registry study on Kawasaki Disease with coronary artery aneurysm
6. Basic study on the profile changes of umbilical cord blood and umbilical cord-derived mesenchymal stem cells in various intrauterine environments
7. Investigation of profile changes in stem cells from human exfoliated deciduous teeth (SHED) in children with

cerebral palsy due to periventricular leukomalacia
8. Elucidating the molecular mechanisms of gonadal development
9. Molecular pathology of congenital adrenal diseases and disorder of sex development
10. Establishment of a patient registry, treatment markers, and a simple genetic test method for 21-hydroxylase deficiency
11. Establishing novel therapeutic approach to congenital hyperinsulinemia
12. Molecular pathology of diabetes mellitus caused by mutations of the insulin receptor
13. Study of autoimmunity in Opsoclonus Myoclonus Syndrom
14. Development of gene therapy for Ataxia Telangiectasia
15. Study of molecular biology in systemic vascular stenosis
16. Genetic background of leukemia development
17. Study using single cell sequencing analysis in pediatric leukemia
18. Development of novel CAR-NK cell therapy for child cancer
19. Identifying the molecular pathology of metabolic syndrome in 21 hydroxylase deficiency
20. 3D genome structure and molecular mechanism in leukemia
21. Mechanistic insight into activation of super-enhancer in T cell commitment
22. Genetic analysis and development of therapeutic approach for epilepsy syndrome
23. Clarifying immunological profiles of the patients with autoimmune diseases
24. Developing a methodology for the diagnosis of cytokine storm syndrome by exploiting a novel biomarker
25. Development of newborn screening for treatable childhood diseases including spinal muscular atrophy
26. Kinetic and functional analysis of novel T and B cell subsets in patients with autoimmune disease
27. Research in pathophysiology and prognostic predictor of nephritis /nephrotic syndrome
28. Molecular mechanisms and pathology of kidney disease with IEI or hereditary kidney disease
We are collaborating with Medical Research Institute at TMDU, Tokyo University, Institute of Medical Sci- ence, Hiroshima University, University of Queensland (Prof. Peter Koopman), Erasmus University (Prof. Jacques van Dongen), Yonsei University (Profs. H. Kim, and SK Lee), Sony Life Science Laboratories, National Institute for Longevity Sciences, National Research Institute for Child Health and Development, RIKEN Center for Integrative Medical Science, Kazusa DNA Research Institute, Tokyo Metropolitan Institute for Medical Science, Juntendo University, Kyoto University, Tokyo University and many other laboratories.

● Hematology/Oncology/Immunology Group (Basic Research) Immunology
We have explored inborn error of immunity (IEI) candidate genes using the whole-exome analysis (WES) method using next-generation sequencers and have identified several candidate mutations. Molecular characterization of these candidates has also been conducted parallelly. We reported that compound heterozygosity for two variants in the RAD50 gene is associated with bone marrow failure and B-cell immunodeficiency (Takagi, Hoshino, Kanakane). Also, we are working with domestic and overseas researchers to analyze the pathogenesis of IEI and to develop therapeutic methods. An international investigation reported that hematopoietic stem cell transplantation could serve as an alternative curative treatment for X-linked agammaglobulinemia (XLA), for which immunoglobulin replacement therapy has been the conventional treatment (Nishimura, Kanegane). A phase II clinical trial is underway to evaluate the efficacy and safety of sirolimus in the treatment of lymphoid enlargement, enteritis, and cytopenia associated with patients with IEI (Isoda). As adoptive immunotherapy to promote immunological reconstitution after transplantation, we have developed virus-specific T cell therapy for refractory viral infections and are pursuing the clinical trial (Kamiya and Morio).
Oncology
A study conducted multi-omics analysis using single-cell technologies to elucidate the origin of Myeloid/NK precursor acute leukemia, revealing it as a distinct independent disease concept. (Nishimura, Takagi).

●Cardiology Group
＜ Basic Research ＞
We are struggling to elucidate the mechanism of pulmonary arterial hypertension. Our current project is to examine a role of BMP9 in PAH. (Sakurai and Hosokawa)

＜ Clinical Research ＞
“Multicenter Registry for pediatric pulmonary arterial hypertension (PAH) (Congenital Heart Disease related PAH (JACPHR) and Idiopathic/heritable PAH (JAPHR))”

“Multicenter Registry study on Kawasaki Disease with coronary artery aneurysm”

●Neurology Group
＜ Basic research ＞
We are trying to establish the gene therapy using viral vectors for ataxia telangiectasia (AT), one of the major neurodegenerative diseases. Another project is to establish diagnostic tools for early detection and early treatment of spinal muscular atrophy (SMA). We are also investigating the pathological mechanism of Moyamoya syndrome.
To clarify the cytoprotective effects of astrocytes in oxygen-glucose deprivation condition, we are investigating the role of nuclear receptor 4A (NR4A) subfamily and another cytoprotective transcription factor related to hypoxia-induced factor-1 α (HIF-1 α) with murine astrocyte-enriched cultures (collaborative project with Hiroshi Sakuma, Tokyo Metropolitan Institute of Medical Science).
＜ Clnical research ＞
“Genetic analysis and development of therapeutic approach for epilepsy syndrome”(collaboration with Showa University)
“Research for rare epilepsy syndrome” (collaboration with Institute of Epilepsy and Neurological Disorders) “Systematic measurement and functional analysis of autoantibody in immunologic neurological diseases” (col- laboration with Tokyo Metropolitan Institute of Medical Science)
“Evaluation of adrenocortical function in the patients with West syndrome treated with ACTH therapy” “Development of newborn screening for treatable childhood diseases including spinal muscular atrophy” “Establishment of quantitative evaluation of pediatric cerebellum-dependent motor learning through prism adaptation and the application to central nervous system diseases”

●Endocrinology – Metabolism Group
Molecular mechanisms of gonadal development
Our current research focuses on elucidating the molecular mechanisms of sex determination and gonadal development, especially in the aspect of the transcriptional network of sex determination and gonadal development. The study will lead to the development of a novel approach to diagnosis and a therapeutic approach to differences in sex development. Another target is to identify the precise functions of transcription factors, such as NR5A1 (SF1), FOXL2, and SOX9, in gonadal development.
Molecular analysis of pathological mechanisms in congenital adrenal hyperplasia (CAH), including developing a novel methodology for analyzing the responsible gene, CYP21A2.
One of our major tasks is supervising the CAH neonatal mass screening in Tokyo. Currently, large number of CAH patients we treat, and clarifying the clinical details and we are focusing on clarifying the long term prognosis of the disease. In addition to adrenal insufficiency and androgen excess, metabolic syndrome during adulthood is reported to be another major concern of CAH. The precise pathophysiology is not known. We are establishing a registry system of 21-OHD patients to develop a novel approach for preventing comorbidities in adulthood.
Identifying novel molecules of congenital endocrinological and congenital metabolic diseases
We aim to identify novel molecules responsible for development of congenital endocrine disorders such as insulin resistance.
Current ongoing projects will be integrated systematically, and will be applicable to develop innovative approach for the treatment of congenital endocrine and metabolic disorder, including regenerative medicine.

●Rheumatology group
We are establishing an evidence based guideline of pediatric rheumatoid diseases including juvenile idiopathic arthritis: JIA. Developing a novel database system, CoNinJa（Children’s version of National Database of Rheumatic Diseases by iR-net in Japan）, clarifying immunological profiles of the patients with autoimmune diseases, developing a methodology for the diagnosis of cytokine storm syndrome by exploiting a novel biomarker, and Kinetic and functional analysis of novel T and B cell subsets in patients with autoimmune disease are other our current projects. In addition, in joint research with the department of rheumatology, we are analyzing the current status and effectiveness of treatment for childhood and adult onset of collagen disease.

●Neonatology group
We will compare and analyze the gene expression profiles of mesenchymal stem cells collected from umbilical cords and dental pulp to elucidate their relationship with disease establishment and to accumulate basic data for cell therapy.
We will collect umbilical cord-derived mesenchymal stem cells with various background factors, such as intrauterine infection and fetal growth restriction, and examine the relationship between profile changes and disease establishment.
As basic data for exploring the possibility of dental pulp stem cell therapy for periventricular leukomalacia, a complication of preterm infants, we are collecting stem cells from human exfoliated deciduous teeth of children with cerebral palsy due to periventricular leukomalacia and analyzing their profile.

●Allergy Group
One of our main project goals is to elucidate the immunological mechanisms of food allergy such as that against cow’s milk, hen eggs, wheat, tree nuts and so on. In addition, we carry out immunological and epidemiological studies on therapeutic effects of oral immunotherapy against food allergy.

●Nephrology Group
Research in pathophysiology and prognostic predictor of nephritis /nephrotic syndrome
A multicentre study with associated hospitals is underway to identify disease pathogenesis and pathogenic factors by analysing patient epidemiological data, peripheral blood cell fraction analysis and serum, urinary protein and miRNA profiling.
Searching for biomarkers associated with the severity, response to treatment and long-term prognosis of idiopathic nephritis and idiopathic nephrotic syndrome, aiming to construct disease models and elucidate the molecular basis of the disease using organoids.

Block Lecture
The systematic lecture was performed for M4 students. One third of the lectures “were performed using an active-learning” style. Nineteen asynchronous lectures for students to review, nine frames of the active-learning and two frames of team -based learning (TBL) were provided. Although one frame of active-learning alone cannot cover the whole area of pediatrics, we believe that the active learning is very useful because it can enhance students’ application skills.
Project semester
This provides the opportunities of basic research for the 4th grade students for half a year. Every year, a few students are committed to the research of our department and presented at a scientific meeting.
Pre-clinical clerkship (PCC).
We proposed 6 programs providing the opportunities to learn the logical skills of clinical practice. After the curriculum, The students undertake the examination of clinical practice, i.e., OSCE , CBT.
Clinical clerkship (CC)
Clinical clerkship (CC) for 5th-year medical students in pediatrics was shortened from 1 month (4 weeks) to 2 weeks due to the pandemic of COVID-19. Each student spent two weeks in one of the two groups (hematology, immunology, cardiology, neurology, Endocrinology-metabolism, nephrology, Rheumatology, neonatology).
Lectures were given to all students six times in two weeks selected from a lot of topics such as diagnostics, congenital heart disease, neonates, infusion, EEG, endocrinology, leukemia, immunodeficiency infections, and the role of the Child Life Specialist in pediatrics, and student conferences were held on Tuesday, Wednesday, and Thursday for further understanding of the clinical practice program.
We struggled to provide ward practice to the students even though the time to practice was limited due to the pandemic.
Two 6th-year medical students were accepted for clinical training in pediatrics, and they joined a practice for two weeks in a medical group of their choice as an advanced program.
In terms of post-graduate education, at least one month of basic clinical education was provided to the first and second year of clinical residents at on-campus. For the second semester clinical residents at the university, we provided a wide range of more specialized clinical education to prepare them to become pediatric specialists.

Primary care of pediatrics covers a wide spectrum of health care and clinical problems in children, and all pediatricians should be well trained in those subjects. Further, Tokyo Medical and Dental University is one of

the top raked national medical universities in Japan, and achieving cutting edge research is another social
responsibility. For students, we provide educational programs to learn primary pediatric care, management of the diseases in every organ during neonatal period childhood, and basic science. For residents, our educational program is mainly focused on producing physician scientists who possess the skills of pediatrics for primary care, of physician specialist and of basic researcher.

●Hematology/Oncology/Immunology Group
Treating children with inborn errors of immunity, hematological malignancies, hematological disorders, and malignant solid tumors.
Collaboration with other professional facilities including St. Luke’s International Hospital and Juntendo University Hospital. Joint clinical conference and trainee exchange program are regularly held in the collaborating system.
Medical care
By collaborating with national co-operative clinical research group, such as the Tokyo Children’s Cancer Study Group (TCCSG) and Japanese Children’s Cancer Study Group (JCCG), we offer our patients opportunities to participate in the latest clinical trials, contributing to establishment of both standard and novel therapies for childhood cancers and other non-malignant diseases.
In FY2023, we performed HCT for 8 cases (6 allo-HCT, 2 auto-HCT). In addition, Two HCTs were performed in collaboration with the hematology department.
For a relapsed ALL case, CAR-T cas performed.
Our experience of HCT exceeds 230 cases including more than 100 cases with primary immunodeficiency diseases, so far.
Clinical trial
Clinical trials led by the pediatric department of Tokyo Medical and Dental University are ongoing.
“Phase 2 study of the efficacy and safety of sirolumus in patients with primary immunodeficiency”
“Cell therapy for treatment-resistant viral infections after hematopoietic cell transplantation using antigen-specific T cells against multiple viruses generated from blood donors with at least half-matched HLA” Clinical trial (Phase I/II) as a GCTP-compliant regenerative medicine technology based on the Law for Ensuring the Safety of Regenerative Medicine.
“Clinical Phase II Study of hematopoietic stem cell transplantation for ataxia telangiectasia and related dis- eases ” is carried out”

●Cardiology Group
We provide medical care in a wide range of pediatric cardiovascular diseases. Especially, our department is one of the major center hospitals providing medical care of pediatric pulmonary hypertension.
In 2023, the number of inpatients was 103, which consisted of 42 congenital heart disease, 17 pulmonary hypertension, 8 Kawasaki Disease (acute treatment), 11 coronary aneurysm with Kawasaki disease (follow up) 7 arrhythmia, and so on. Cardiac catheterizations were performed in 56 patients and cardiac surgery was performed in 16 patients (open-heart surgery).

●Neurology Group
We provide medical care in a wide range of pediatric nerologic diseases.
In particular, collaborating with the department of neurosurgery, we run an epilepsy center, providing advanced
medical care for pediatric patients with intractable epilepsy.
The medical services in our department are long-term video EEG monitoring, high magnetic field MRI/PET, ACTH therapy, ketogenic diet, vagus nerve stimulation and surgical operation, such as focal brain resection and callosotomy. We also provide nucleic acid drug and gene therapy for patients with spinal muscular atrophy. We focus on diagnosis, genetic analysis and treatment for rare neurologic diseases.

●Endocrinology- Metabolism Group
We provide comprehensive diagnostic and treatment services for children with disorders of endocrinology and metabolism, including diabetes, such as disorders of growth, pubertal development, Ca/P metabolism.
(including skeletal dysplasia), gonadal development and adrenal cortex function. We are especially focusing on providing advanced medical services for congenital adrenal hyperplasia (CAH) and disorders of sex development (DSD). Our institute is one of the DSD central facilities approved by the Japanese Society for Pediatric Endocrinology (JSPE). For social contribution, we supervise the neonatal screening system for CAH in Tokyo metropolitan city and peer support group of type 1 diabetes, “Tokyo Wakamatsu-kai”

●Nephrology Group
Nephrology Group provides diagnosis and treatment for patients with various kidney diseases. We perform kidney biopsy (30/year) and imaging examination. Percutaneous needle renal biopsy under general anaesthesia is performed in patients with nephritis and nephrotic syndrome in infancy, in collaboration with anaesthetists. Last year, seven percutaneous needle renal biopsies under general anaesthesia were performed. No major complications occurred and the procedure was performed safely.
We performed peritoneal dialysis for infants and provided acute hemodialysis for children who developed acute kidney injury. Also patients with tubulointerstitial nephritis and renal disease complicated by uveitis are treated.

●Rheumatology group
We treat children with rheumatic diseases, undiagnosed cases such as fever of unknown origin, and autoinflammatory syndrome represented by periodic fever. The emphasis is on the issues and challenges of transitional care in adulthood for pediatric rheumatic diseases.

●Neonatology group
Collaborating with other medical departments or special care groups in pediatrics, we are treating preterm in- fants (≧ 27 weeks gestation, birth weight ≧ 800 g), neonates with complications and babys born from mothers with complication.

●Allergy Group
The qualified allergists of the group attend both inpatient and outpatient care units for allergic diseases in the allergy medical center of our university and extramural, affiliated hospitals, where not only the standard medical services following clinical guidelines for allergic diseases are provided, but also highly advanced treatment such as oral immunotherapy for food allergy as well.

●Hematology-Oncology/ Immunology Group
Hematology-Oncology/ Immunology Group provides diagnosis, treatment and pathological analysis of hemato- logical malignancies and inborn errors of immunity. We perform hematopoietic stem cell transplan- tation for refractory diseases. Specifically, we treat the largest number of primary immunodeficiency disease patients in Japan. We participate in multi-center cooperative clinical research to establish both standard and novel therapies for childhood cancers, and also participate in the approval of industry-based clinical trials for drugs (such as anticancer drugs).

●Cardiology Group
Cardiology group performs diagnosis, evaluation of treatment and decision of treatment strategy for pediatric pulmonary hypertension patients. We actively treat severe idiopathic/hereditary pulmonary arterial hypertension (IPAH/HPAH) patients by upfront combination therapy (uCT) with two or three kinds of disease targeted drugs including continuous venous infusion of epoprostenol. We made considerable achievements of treatment in severe IPAH/HPAH patients with epoprostenol/treprostinil.

●Neurology Group
Neurology group provide highly specialized diagnostic approach and medical care for neurological disorders such as incractable epilepsy, cerebellar ataxia, immune-mediated neurological disease, spinal muscular atrophy, involuntary movement, perinatal brain damage, infection of nervous system, acute encephalopathy/encephalitis, neurodegenerative disease.

●Endocrinology- Metabolism Group
The leader of our endocrinology group is a supervisor of congenital adrenal hyperplasia (CAH) newborn screen- ing in Tokyo. We treat substantial number of CAH (21-OHD) patients and performed couples of clinical studies. We also focus on differences in sex development (DSD) and long-term follow-up for childhood cancer survivors (CSS). We are organizing a Type 1 DM patients’ association (Wakamatsu-kai) and have a summer camp for diabetic children every year.

●Nephrology Group
We treat various pediatric kidney diseases, such as congenital nephrotic syndrome, refractory nephrotic syn- drome, IgA nephropathy, Henoch-Scho ¨ nlein purpura nephritis and tubulointerstitial nephritis with or without uveitis, etc. Chronic kidney disease management and dialysis treatment for children with acute renal failure. Acute hemodialysis and plasma exchange therapy for acute renal failure associated with hematological disease and collagen diseases, as well as autoimmune encephalitis, are also provided. Needle kidney biopsy performed to more than 30 patients for infants and over children. We cpoperate in school urinalysis to prevent exacerbations of renal disease, we

●Rheumatology group
Clinically, our target is not only pediatric rheumatic disease, but also inflammatory diseases such as periodic fever, fever of unknown origin, and repeated arthritis affecting multiple joints. We are also actively involved in the expansion and standardization of treatment indications through participation in clinical trials and formulation of guidelines.

●Neonatology Group
Our NICU provides intensive care for preterm infants and critically ill newborns. As a designated perinatal medical center in Tokyo, we accept maternal and neonatal transfer from various areas in Tokyo and contribute to perinatal medicine in Tokyo.

●Allergy Group
We focus on clinical care of severe and complicated allergic diseases such as food allergy-induced anaphylaxis, food-dependent exercise-induced anaphylaxis, food protein-induced enterocolitis syndrome and oral allergy syn- drome induced by cross-reactivity between food, inhalant and contact allergens. We extensively perform food challenge tests not only for correct diagnosis of food allergy but for preparation of oral immunotherapy in cooperation with the affiliated hospitals. We introduce new biological medicines to the long-term management for sever persistent asthma patients.