Alliance Laboratory for Advanced Medical Research (Alliance Station)
－Collaboration Framework for Drug Discovery Research with Astellas ―

There are still many unmet medical needs in the world including those of intractable diseases and rare diseases. Due to their complexity and rarity, mechanisms of these diseases are more difficult to be clarified, and drug discovery for these diseases requires an understanding of disease pathologies in humans. Thus, researches using blood and other clinical samples to identify molecules and cells critically associated with patients’ diseases, and those determining patient stratification are being highly demanded. In order to exploit findings of these studies and deliver innovative drugs to patients as soon as possible, efficient and in-depth research collaborations between academia and pharmaceutical company are needed in situations close to the clinical setting and diseases.
To further accelerate drug discovery research through evolution of the open innovation system of the AK Project*, where, clinical and basic research of the university and drug discovery research of the company are closely linked in a timely manner, Kyoto University and Astellas established Alliance Station (A-Station), a new open innovation scheme at Kyoto University, and the Alliance Laboratory for Advanced Medical Research as a framework for the implementation of its activities. A-Station is a new platform for collaboration between industry and academia and under this scheme, Kyoto University and Astellas will conduct joint research projects in all therapeutic areas in a prompt and flexible manner. Director： Shuh Narumiya （Professor, Graduate school of Medicine）
Industrial Partner： Astellas Pharma Inc.* AK Project: Collaborative research conducted by Kyoto University and Astellas from July 2007 to March 2017 in “Center for Innovation in Immunoregulative Technologies and Therapeutics” as a “Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program” funded by the the Ministry of Education, Culture, Sports, Science and Technology.

https://www.a-station.med.kyoto-u.ac.jp/（On-campus only）

Department of Drug Discovery for Lung Diseases

In the era of an aging society, lung diseases such as pulmonary fibrosis, lung cancer, COPD, bronchial asthma and pneumonia have an increasing impact on healthy life expectancy. Although more than two trillion yen is spent for lung diseases each year in Japan, the therapeutic agents for lung diseases are still limited. We think that one of the reasons is the complexity of human lung structure, consisting of various cells and matrices forming numerous tracheal branches and >300 million alveoli with elaborate network of blood vessels. However, the recent progress in human lung cell biology has made it possible to initiate this project of drug discovery for refractory lung diseases under the collaboration of academic and industrial researchers in Kyoto University.

Department of Advanced Medicine for Respiratory Failure

Respiratory failure is caused by various conditions, including the impairment of gas exchange due to lung injury, pump failure of respiratory muscles, and abnormal ventilatory control. Respiratory failure is an important disease condition, because it can impair healthy life expectancy. In addition to drugs, respiratory rehabilitation, and surgeries such as lung transplantation, chronic respiratory failure treatment includes oxygen therapy and noninvasive ventilation (NIV).
Home health care, including home oxygen therapy (HOT), is an important part of chronic respiratory failure treatment. The number of patients on HOT has increased steadily to 140,000 in 2014, and the primary users are elderly patients with an average age >70 years. This trend will likely continue because Japan is experiencing a “super-aging” society.
The development of telecommunications equipment has enabled us to establish telemedicine, including telemonitoring. Telemonitoring has attracted interest as a potential solution to provide care for increasing aging populations living with chronic respiratory failure, particularly HOT users. In Japan, payment for “remote patient monitoring” was newly added to the medical payment system in 2018. Despite the increasing importance of home health care and telemedicine for chronic respiratory failure, a system to collect useful bioinformation has not yet been established. The aim of this department is to improve the management of respiratory failure by establishing a telemonitoring system through the collaboration of the Kyoto University Hospital and Teijin Pharma Ltd.

Department of Clinical Bio-resource Research and Development

For medical research and development, clinical samples are emerging to play important roles in every phase throughout the entire process. Moreover, clinical sample is one of the most valuable resources for assessing interpatient heterogeneity to achieve precision and personalized medicine. Thus, analysis on clinical samples become more and more critical for clinical practice as well as R&D. Kyoto university has built up KBBM, Inc. teaming up with 7 private companies to ensure ethics and quality in collection, transfer and preservation of clinical samples. These supports by KBBM are going to be applied to all the clinical samples and medical information associated with them, including healthy controls, collected through the Clinical Bioresource Center in Kyoto university hospital. Accordingly, medical research and development in Kyoto university will be further promoted by taking advantages of easily accessible and quality controlled clinical samples and their data.
The researchers in our department have developed and improved methods for the preparation, culture and application of cancer cells as well as normal cells from patient samples. We are currently working on establishing panels of the cultured cancer cells from different patient samples. By integrating information including ex vivo chemo/radio-sensitivity assay, in vivo assay, clinical course, genome sequencing, OMICS data, and so on, we aim to develop novel targets of therapy, and biomarkers for selecting suitable therapeutics for each patient. We keep promoting innovation in the technology of culturing patient-originated cells to truly realize personalized medicine.

https://cbrrd.med.kyoto-u.ac.jp/en/index_en.html

Next-generation Oncology Discovery

under construction

Department of Epilepsy, Movement Disorders and Physiology

Department of Epilepsy, Movement Disorders and Physiology was established as an Endowed Department in August 2013, supported by the Department of Neurology (chaired by Prof. Ryosuke Takahashi), and has been continuing as the Industry-Academia Collaboration Course since June 2018. We keep working on clinical research to solve pathomechanism of epilepsy and movement disorders, developments of new treatments from the aspect of neurons and glia, and translatable and translational research under close collaboration with basic scientists. We also provide a wide range of educational opportunities to physicians and clinical researchers internationally.

1. ​We started joint clinical researches (with Eisai Co., Ltd.) to elucidate the property of paroxysmal depolarization shift (PDS) at epileptic foci in human and to individualize inhibitory mechanism of anti-epileptic/seizure drugs which have direct and/or indirect effects on PDS, such as AMPA antagonist. We also aim to elucidate pathomechanism of neurological disorders in which neurons and glia underlying, and develop the precisional treatments.
   The followings are our continuous activities since 2013 of establishment (supported by NIHON KOHDEN, Otsuka Pharmaceutical., and UCB Japan).
2. ​Clinical activities and education
   We aim to solve pathophysiology of epilepsy and movement disorders, and to develop new treatments that could lead to the advanced medical care. We also aim at standardizing it in clinical practice. We provide integrated teaching opportunities for training of physician-scientists, clinical specialists, and leaders of related fields internationally.
3. ​Research activities
   We promote clinical practice and research of clinical neurophysiology on epilepsy and movement disorders and its clinical application, which are very closely related to neurophysiological knowledge and methods.

http://epilepsy.med.kyoto-u.ac.jp/?lang=en

Department of Advanced Imaging in Medical Magnetic Resonance

under construction

Department of Regulation of Neurocognitive Disorders

Department of Regulation of Neurocognitive Disorders
– Alliance between Japanese-founded U.S. Bio Ventures (Cyn-K, LLC & VLP Therapeutics, LLC) and Department of Neurology of Kyoto University Graduate School of Medicine –
As Japan entered a rapidly aging society and the number of people with neurocognitive disorders continues to increase, finding measures to address them has become urgent matters for the whole country. In particular, patients with neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease are increasing in number depending on the age, however there is still no fundamental treatment for such neurocognitive disorders. In our department, we will use the platform technology discovered and developed by VLP Therapeutics (USA), co-founded by our industry collaborator, and investigate the effects of the vaccine targeting a pathogenesis protein associated with neurocognitive disorders on such disorders, as well as elucidate the mechanism of brain degeneration and aging. We think it better to have vaccines for the treatment of neurocognitive disorders. They offer not only economic advantage but also objective indexes such as antibody titers that can be used to measure the effects. Furthermore, they eliminate the concerns for elderly patients with neurocognitive disorders to forget to medicate or to over-medicate themselves. Vaccines offer overwhelming benefits over drugs that need to be taken daily, or the expensive antibody medicines. We aim to develop three types of vaccines according to the progression of the disease.

Department of Real World Data Research and Development

Department of Real World Data Research and Development Web Site

Immunology and Genomic Medicine

We have been studying molecular mechanisms controlling development and function of lymphocytes. Currently we are addressing important questions:

1. ​How antibody diversity is controlled by AID, a putative RNA-editing enzyme required for class switch recombination (CSR) and somatic hypermutation (SHM)? We found that AID reduces the amount of Topoisomerase 1, generating non-B DNA and inducing irreversible cleavage by Topoisomearse 1.
2. ​How PD-1 deficiency leads to development of autoimmune diseases? Why a fraction of cancer patients are not sensitive to the PD-1 blockade cancer immunotherapy. ＜Research and Education＞
   We proved that class switch is mediated by recombination with dynamic excision of genomic fragments. In 2000, we discovered activation-induced cytidine deaminase (AID), which is responsible for DNA cleavage to initiate both CSR and SHM. Surprisingly, AID mutates not only the antibody gene, but also protooncogenes. We have found that topoisomerase 1 (Top1) is the enzyme that initiates CSR and SHM by cleaving S and V region, respectively. Furthermore, the transcription coupled nucleosomal reassembly is critical for this Top1-mediated DNA cleavage during CSR and SHM.
   Recently, clinical trials of humanized anti-PD-1 antibody against melanoma, renal cancer and lung cancer demonstrated that PD-1 blockade can cure cancer mediated by tumor-reactive T cell activation. Although anti-human PD-1 antibody (Nivolumab) has been approved for the above cancers, more than half patients were still unresponsive. PD-1 blockade leads not only anti-cancer immunity, but also autoimmunity. The aim of our research is to elucidate how PD-1 control the anti-tumor or auto-immunity and to regulate the sensitivity for the PD-1 blockade cancer immunotherapy.

http://www2.mfour.med.kyoto-u.ac.jp/en/index.html

Department of Digital Health and Epidemiology