RIKEN Center for Integrative Medical Sciences Laboratory for Pharmacogenomics
Team Leader: Taisei Mushiroda (Ph.D.)
The Laboratory for Pharmacogenetics aims to identify genes associated with drug efficacy and adverse drug reactions, leading to the establishment of personalized therapeutics based on pharmacogenomics.
A combination of genetic variations and environmental differences defines unique human characteristics, including individual responsiveness (effectiveness and adverse reaction) to drugs. Among several types of genetic variation, single-nucleotide polymorphisms (SNPs) are the most abundant throughout the genome. SNPs have lately received much attention in biomedical fields, because some of them can influence the quality and/or the quantity of particular gene products, and thereby serve as markers of individual risk for adverse drug reactions or susceptibility to complex diseases. We expect the genomic approach, by exploiting an already large collection of SNPs and haplotype maps based on that collection, to revolutionize drug discovery and development, as well as the practice of medicine, within the next 5-10 years. Genetic variations in genes encoding proteins involved in drug metabolism, transport and response are of increasing importance for selecting particular drugs and an optimal dosages to provide the maximum effect and minimal adverse reactions for individual patients. The SNP-based approach makes us confident of achieving one of our goals, which is establishment of 'personalized medicine' that can provide the right drug at the appropriate dose for each individual patient.
Main Research Fields
- Medicine, Dentistry & Pharmacy
- Genomic biomarker
- Drug response
- Adverse drug reaction
- Germline genetic testing
Kawamura T, Imamura CK, Kenmotsu H, Taira T, Omori S, Nakashima K, Wakuda K, Ono A, Naito T, Murakami H, Mushiroda T, Takahashi T, Tanigawara Y.:
"Evaluation of gefitinib systemic exposure in EGFR-mutated non-small cell lung cancer patients with gefitinib-induced severe hepatotoxicity"
Cancer Chemother Pharmacol 85, 605-614 (2020).
Nakamura R, Ozeki T, Hirayama N, Sekine A, Yamashita T, Mashimo Y, Mizukawa Y, Shiohara T, Watanabe H, Sueki H, Ogawa K, Asada H, Kaniwa N, Tsukagoshi E, Matsunaga K, Niihara H, Yamaguchi Y, Aihara M, Mushiroda T, Saito Y, Morita E.:
"Association of HLA-A*11:01 with Sulfonamide-Related Severe Cutaneous Adverse Reactions in Japanese Patients"
J Invest Dermatol 140, 1659-1662 (2020).
Tamura K, Imamura CK, Takano T, Saji S, Yamanaka T, Yonemori K, Takahashi M, Tsurutani J, Nishimura R, Sato K, Kitani A, Ueno NT, Mushiroda T, Kubo M, Fujiwara Y, Tanigawara Y.:
"CYP2D6 Genotype-Guided Tamoxifen Dosing in Hormone Receptor-Positive Metastatic Breast Cancer (TARGET-1): A Randomized, Open-Label, Phase II Study"
J Clin Oncol 38, 558-566 (2020).
Hikino K, Ozeki T, Koido M, Terao C, Kamatani Y, Mizukawa Y, Shiohara T, Tohyama M, Azukizawa H, Aihara M, Nihara H, Morita E, Murakami Y, Kubo M, Mushiroda T.:
"HLA-B*51:01 and CYP2C9*3 Are Risk Factors for Phenytoin-Induced Eruption in the Japanese Population: Analysis of Data From the Biobank Japan Project"
Clin Pharmacol Ther 107, 1170-1178 (2020).
Suvichapanich S, Wattanapokayakit S, Mushiroda T, Yanai H, Chuchottawon C, Kantima T, Nedsuwan S, Suwankesawong W, Sonsupap C, Pannarunothai R, Tumpattanakul S, Bamrungram W, Chaiwong A, Mahasirimongkol S, Mameechai S, Panthong W, Klungtes N, Munsoo A, Chauychana U, Maneerat M, Fukunaga K, Omae Y, Tokunaga K.:
"Genomewide Association Study Confirming the Association of NAT2 with Susceptibility to Antituberculosis Drug-Induced Liver Injury in Thai Patients"
Antimicrob Agents Chemother 63, e02692-18 (2019).
Fujimori S, Fukunaga K, Takahashi A, Mushiroda T, Kubo M, Hanada R, Hayashida M, Sakurai T, Iwakiri K, Sakamoto C.:
"Bactericidal/Permeability-Increasing Fold-Containing Family B Member 4 May Be Associated with NSAID-Induced Enteropathy"
Dig Dis Sci 64, 401-408 (2019).
Yoshihama T, Fukunaga K, Hirasawa A, Nomura H, Akahane T, Kataoka F, Yamagami W, Aoki D, Mushiroda T.:
"GSTP1 rs1695 is associated with both hematological toxicity and prognosis of ovarian cancer treated with paclitaxel plus carboplatin combination chemotherapy: a comprehensive analysis using targeted resequencing of 100 pharmacogenes"
Oncotarget 9, 29789-29800 (2018).
Suvichapanich S, Fukunaga K, Zahroh H, Mushiroda T, Mahasirimongkol S, Toyo-Oka L, Chaikledkaew U, Jittikoon J, Yuliwulandari R, Yanai H, Wattanapokayakit S, Tokunaga K.:
"NAT2 ultra-slow acetylator and risk of anti-tuberculosis drug-induced liver injury: a genotype-based meta-analysis"
Pharmacogenet Genomics 28, 167-176 (2018).
Mushiroda T, Takahashi Y, Onuma T, Yamamoto Y, Kamei T, Hoshida T, Takeuchi K, Otsuka K, Okazaki M, Watanabe M, Kanemoto K, Oshima T, Watanabe A, Minami S, Saito K, Tanii H, Shimo Y, Hara M, Saitoh S, Kinoshita T, Kato M, Yamada N, Akamatsu N, Fukuchi T, Ishida S, Yasumoto S, Takahashi A, Ozeki T, Furuta T, Saito Y, Izumida N, Kano Y, Shiohara T, Kubo M; GENCAT Study Group.:
"Association of HLA-A*31:01 Screening With the Incidence of Carbamazepine-Induced Cutaneous Adverse Reactions in a Japanese Population"
JAMA Neurol 75, 842-849 (2018).
Ujiie H, Muramatsu K, Mushiroda T, Ozeki T, Miyoshi H, Iwata H, Nakamura A, Nomoto H, Cho KY, Sato N, Nishimura M, Ito T, Izumi K, Nishie W, Shimizu H.:
"HLA-DQB1*03:01 as a Biomarker for Genetic Susceptibility to Bullous Pemphigoid Induced by DPP-4 Inhibitors"
J Invest Dermatol 138, 1201-1204 (2018).
- Taisei Mushiroda
- Team Leader
- Takeshi Ozeki
- Research Scientist
- Koya Fukunaga
- Research Scientist
- Keiko Hikino
- Research Associate
1-7-22 Suehiro-cho, Tsurumi-ku,
Yokohama City, Kanagawa,
Email: mushiroda [at] riken.jp