Hashimoto Lab

About

Mission

Our research group is focusing on the roles of angiogenesis and vascular remodeling in vascular diseases including, intracranial aneurysms, aortic aneurysms, and brain arteriovenous malformations. These vascular lesions usually remain asymptomatic until they rupture. In case of intracranial aneurysms, rupture results in subarachnoid hemorrhage that can potentially cause severe mortality and morbidity.

Prevention of rupture of these vascular lesions is critical. We are working to identify new therapeutic targets that induce stabilization and regression of vascular lesions so that they remain unruptured and asymptomatic. We utilize novel animal models and human specimens to achieve these goals.

Current Research Topics:

Intracranial aneurysms
Aortic aneurysms
Brain arteriovenous malformations

 

 

 

 

 

Research

Intracranial aneurysms and Aortic aneurysms

An aneurysm is an abnormal widening or ballooning of a portion of an artery due to weakness in the blood vessel wall. Two common locations for aneurysms are intracranial arteries and the aorta. Despite recent advancements in the diagnosis and treatment of aneurysms, mechanisms for the formation, development and subsequent rupture of aneurysms are not well understood. Current treatment involves surgical intervention for unruptured aneurysms. However, this still carries significant risk of mortality and morbidity.

Our goal is to identify new therapeutic approaches that induce stabilization of aneurysms to prevent aneurysmal rupture. In order to develop a strategy to select and timely employ potential pharmacological treatments, we utilize unique animal models that were developed in our lab. Aneurysms in our animal models recapitulate key features of human aneurysms. In addition, some of these aneurysms rupture, closely mimicking human pathophysiology. Using novel animal models and human aneurysmal tissues, we are testing various molecular targets that will help us understand the mechanisms associated with aneurysm development.

 

IA2.jpg

Representative intracranial aneurysm in our mouse model.
Aneurysms in this model recapitulate key features of human intracranial aneurysms.

 

 

Brain arteriovenous malformations

Brain arteriovenous malformations (AVMs) are complex tangles of abnormal vessels joined by multiple fistulae without an intervening capillary bed. The disease typically affects healthy young adults. The most frequent presentation of AVMs is an intracranial hemorrhage.

AVM formation and growth appear to be a result of concerted effects from various angiogenic factors and matrix metalloproteinases (MMPs). In a collaborative effort with the UCSF Center for Cerebrovascular Research, our group is focusing on determining the consequences of MMP inhibition at the cellular and structural levels to understand the pathophysiology of AVMs.

 

AVMgrp.jpg

Abnormal blood vessels in AVM tissues.
Both venous (arrow) and arterial (arrowhead) vessels are shown.

 
People

Members

Principal Investigator
Tomoki Hashimoto, MD

Researchers
Yoshinobu Kamio, MD - Post-doctoral scholar
Daisuke Kudo, MD, PhD – Post-doctoral scholar
Takeshi Miyamoto, MD, PhD – Post-doctoral scholar

Former Members
Fumiaki Shikada, MD, PhD
Kenji Shimada, MD, PhD
Kosuke Wada, MD
Elena Liang
Yoshiteru Tada, MD, PhD
Hiroshi Makino, MD
Yasuhisa Kanematsu, MD, PhD
Miyuki Kanematsu, MD
Yoshitsugu Nuki, MD, PhD
Chie Kurihara, BS
Erik Tsou, BS
Ryo Ota, MD
Eric Tsang, BS
Melissa Matsumoto, BS
Atsushi Kuwabara, MD - Post-doctoral scholar
Wei Yuan, PhD - Specialist
Hajime Furukawa, MD - Post-doctoral scholar
Masaaki Korai, MD - Post-doctoral scholar
Masakazu Kotoda, MD - Post-doctoral scholar
Kimihiko Yokosuka, MD, PhD - Post-doctoral scholar
Kazuha Mitsui, MD - Post-doctoral scholar
Dingding Zhang, MD, PhD

Tomoki Hashimoto, MD

Tomokiportrait2010.jpg

Tomoki Hashimoto, MD
Principal Investigator

Department of Anesthesia and Perioperative Care
1001 Potrero Avenue, 3C-38
San Francisco, CA 94110
phone: 415-206-8958
fax: 415-206-8170
email:Tomoki.Hashimoto@ucsf.edu 

Education and Training

MD, Gifu University, Japan
Anesthesia Residency, Columbia Presbyterian Medical Center
Neuroanesthesia Fellowship, Columbia Presbyterian Medical Center
American Board of Anesthesiology

Research Interests

Angiogenesis and vascular remodeling in cerebrovascular disease
Anesthetic management for cerebrovascular disease
Anesthetic management for interventional neuroradiology

Selected Publications

Publications

Yoshinobu Kamio, MD

Yoshinobu Kamio, MD 
Post-doctoral Scholar

1001 Potrero Avenue, Box-1371
San Francisco, CA 94110
phone: 415-206-3296
fax: 415-206-8170
email: Yoshinobu.Kamio@ucsf.edu

Education and Training

MD, Hamamatsu University School of Medicine, Japan

Professional Membership

Board Certified, Japan Neurosurgical Society
The Japanese Stroke Society
Japanese Society for Neuroendovascular Therapy

Research Interests

Mechanism of intracranial aneurysmal rupture

Selected Publications

Kamio Y, Sakai N, Takahashi G, Baba S, Namba H: Nasopharyngeal carcinoma presenting with rapidly progressive severe visual disturbance: a case report. J Med Case Rep. 2014;8:361

Kamio Y, Sakai N, Sameshima T, Takahashi G, Koizumi S, Sugiyama K, Namba H: Usefulness of intraoperative monitoring of visual evoked potentials in transsphenoidal surgery. Neurol Med Chir (Tokyo) 2014;54:606-611

Kamio Y, Hiramatsu H, Yamashita S, Kamiya M, Suigura Y, Namba H: Dural Arteriovenous Fistula of the Transverse and Sigmoid Sinus Manifesting Ascending Dysesthesia: Case Report and Literature Review. NMC Case Report Journal 2015;2:4-8

Daisuke Kudo, MD, PhD

Daisuke Kudo, MD, PhD
Post-doctoral Scholar
daisuke.kudo@ucsf.edu

Education and Training

MD, Tohoku University, Japan
PhD, Tohoku University Graduate School of Medicine, Japan
Board certified emergency care physician of Japanese Association for Acute Care Medicine
Board certified critical care physician of the Japanese Society of Intensive Care Medicine
Board certified surgeon of Japan Surgical Society
Board certified trauma surgeon of the Japanese Association for The Surgery of Trauma (Councilor)
Board certified Burn care physician of Japanese Society for Burn Injury

Research Interests

Mechanism of intracranial aneurysmal rupture
Acute inflammation and innate immunity
Coagulation and fibrinolysis
Pathophysiology and clinical approach for sepsis, acute lung injury and trauma

Selected Publications

Daisuke Kudo, Shigeki Kushimoto, Atsushi Shiraishi, Hiroshi Ogura, M.D, Akiyoshi Hagiwara, Daizoh Saitoh, J-OCTET investigators. The impact of pre-injury antithrombotic medication on hemostatic interventions in trauma patients: An observational study in Japan. Am J Emerg Med 2016 Epub ahead of print

Ohbe H, Kudo D (equal contribution), Yamanouchi S, Kushimoto S. Decreased a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 activity and neurologic outcome in patients with successful resuscitation of out-of-hospital cardiac arrest: A prospective observational study. J Crit Care. 2016;37:13-18. PMID: 27610586

Daisuke Kudo, Junichi Sasaki, Satoshi Akaishi, Satoshi Yamanouchi, Tomoaki Koakutsu, Tomoyuki Endo, Takeaki Sato, Ryosuke Nomura, Hironao Yuzawa, Michio Kobayashi, Yotaro Shinozawa, and Shigeki Kushimoto. Original Article: Efficacy of a high FFP:PRBC transfusion ratio on the survival of severely injured patients: A retrospective study in a single tertiary emergency center in Japan. Surgery Today 2014; 44(4): 653-661 PMID: 23420095

Satoshi Yamanouchi, Daisuke Kudo (equal contribution), Mitsuhiro Yamada, Noriko Miyagawa, Hajime Furukawa, and Shigeki Kushimoto. Plasma mitochondrial DNA levels in patients with trauma and severe sepsis: Time-course and the association with clinical status. J Crit Care 2013;28(6):1027-31 PMID: 23787023

Daisuke Kudo, Masahiko Toyama, Tetsuji Aoyagi, Yukiko Akahori, Hideki Yamamoto, Keiko Ishii, Emi Kanno, Ryoko Maruyama, Mitsuo Kaku, Shigeki Kushimoto, and Kazuyoshi Kawakami. Involvement of High Mobility Group Box 1 and the therapeutic effect of recombinant thrombomodulin in a mouse model of severe acute respiratory distress syndrome. Clinical and Experimental Immunology 2013; 173(2): 276-87 PMID: 23607598

Daisuke Kudo, Kazuko Uno, Tetsuji Aoyagi, Yukiko Akahori, Keiko Ishii, Emi Kanno, Ryoko Maruyama, Shigeki Kushimoto, Mitsuo Kaku, and Kazuyoshi Kawakami. Low-dose interferon-α treatment improves survival and inflammatory responses in a mouse model of fulminant acute respiratory distress syndrome. Inflammation 2013; 36(4): 812-20. PMID: 23407996

Takeshi Miyamoto, MD, PhD

Takeshi Miyamoto, MD, PhD 

Education and Training

MD, Tokushima University, Japan
PhD, Tokushima University Graduate School

Professional Membership

Board-certified of The Japan Neurosurgical Society
Member of The Japanese Congress of Neurological Surgeons
Member of The Japanese Society for Neuroendovascular Therapy
Member of The Japan Stroke Society
Member of The Japanese Society of Cerebral Blood Flow and Metabolism
Member of the International Society for Cerebral Blood Flow and Metabolism
Member of the American Physiological Society
Member of the American Heart Association

Research Interests

Translational research of cerebrovascular disease
Intracranial aneurysm

Selected Publications

Miyamoto T, Kung DK, Kitazato KT, Yagi K, Shimada K, Tada Y, Korai M, Kurashiki Y, Kinouchi T, Kanematsu Y, Satomi J, Hashimoto T, Nagahiro S. Site-specific elevation of IL-1β and MMP-9 in the Willis circle by hemodynamic changes is associated with rupture in a novel rat cerebral aneurysm model. J Cereb Blood Flow Metab (in press).

Korai M, Kitazato KT, Tada Y, Miyamoto T, Shimada K, Matsushita N, Kanematsu Y, Satomi J, Hashimoto T, Nagahiro S. Hyperhomocysteinemia induced by excessive methionine intake promotes rupture of cerebral aneurysms in ovariectomized rats. J Neuroinflammation. 2016; 13:165.

Sumiyoshi M, Kitazato KT, Yagi K, Miyamoto T, Nagahiro S. et al. The accumulation of brain water-free sodium is associated with ischemic damage independent of the blood pressure in female rats. Brain Res. 2015; 1616: 37-44.

Sumiyoshi M, Satomi J, Kitazato KT, Yagi K, Shimada K, Miyamoto T, Nagahiro S. et al. PPARγ-Dependent and -Independent Inhibition of the HMGB1/TLR9 Pathway by Eicosapentaenoic Acid Attenuates Ischemic Brain Damage in Ovariectomized Rats. J Stroke Cerebrovasc Dis. 2015; 24: 1187-95.

Matsuzaki K, Uno M, Fujihara T, Miyamoto T, Yokosuka K, Toi H, Matsubara S, Hirano K. Ruptured distal accessory anterior cerebral artery aneurysm--case report. Neurol Med Chir (Tokyo). 2011; 51: 839-42.

 

Publications

Publications via PubMed 

Tada Y, Wada K, Shimada K, Makino H, Liang EI, Murakami S, Kudo M, Kitazato KT, Nagahiro S, Hashimoto T. Roles of Hypertension in the Rupture of Intracranial Aneurysms. Stroke. 2013 Dec 26. PubMed abstract

Takayanagi T, Crawford KJ, Kobayashi T, Obama T, Tsuji T, Elliott KJ, Hashimoto T, Rizzo V, Eguchi S.Caveolin-1 is critical for abdominal aortic aneurysm formation induced by angiotensin II and inhibition of lysyl oxidase. Clin Sci (Lond). 2013 Dec 13. PubMed abstract

Wada K, Makino H, Shimada K, Shikata F, Kuwabara A, Hashimoto T. Translational Research Using a Mouse Model of Intracranial Aneurysm. Transl Stroke Res. 2013 PubMed abstract

Hasan D, Chalouhi N, Jabbour P, Dumont AS, Kung DK, Magnotta VA, Young WL, Hashimoto T, Winn HR, Heistad D. Early change in ferumoxytol-enhanced magnetic resonance imaging signal suggests unstable human cerebral aneurysm: a pilot study. Stroke. 2012 Dec;43(12):3258-65. PubMed abstract

Makino H, Tada Y, Wada K, Liang EI, Chang M, Mobashery S, Kanematsu Y, Kurihara C, Palova E, Kanematsu M, Kitazato K,Hashimoto T. Pharmacological stabilization of intracranial aneurysms in mice: a feasibility study. Stroke. 2012 Sep;43(9):2450-6. PubMed abstract

Tada Y, Kanematsu Y, Kanematsu M, Nuki Y, Liang EI, Wada K, Makino H, Hashimoto T. A mouse model of intracranial aneurysm: technical considerations.Acta Neurochir Suppl. 2011;111:31-5. PubMed abstract

Kanematsu Y, Kanematsu M, Kurihara C, Tada Y, Tsou TL, van Rooijen N, Lawton MT, Young WL, Liang EI, Nuki Y, Hashimoto T. Critical Roles of Macrophages in the Formation of Intracranial Aneurysm. Stroke. 2010 Nov 24. PubMed abstract

Monson KL, Matsumoto MM, Young WL, Manley GT, Hashimoto T. Abrupt increase in rat carotid blood flow induces rapid alteration of artery mechanical properties. J Mech Behav Biomed Mater. 2011 Jan;4(1):9-15. PubMed abstract

Kanematsu Y, Kanematsu M, Kurihara C, Tsou TL, Nuki Y, Liang EI, Makino H, Hashimoto T. Pharmacologically induced thoracic and abdominal aortic aneurysms in mice. Hypertension. 2010 May;55(5):1267-74. PubMed abstract

Nuki Y, Tsou TL, Kurihara C, Kanematsu M, Kanematsu Y, Hashimoto T. Elastase-induced intracranial aneurysms in hypertensive mice. Hypertension. 2009 Dec;54(6):1337-44. PubMed abstract

Ota R, Kurihara C, Tsou TL, Young WL, Yeghiazarians Y, Chang M, Mobashery S, Sakamoto A, Hashimoto T. Roles of matrix metalloproteinases in flow-induced outward vascular remodeling. J Cereb Blood Flow Metab. 2009 Sep;29(9):1547-58. PubMed abstract

Nuki Y, Matsumoto MM, Tsang E, Young WL, van Rooijen N, Kurihara C, Hashimoto T. Roles of macrophages in flow-induced outward vascular remodeling. J Cereb Blood Flow Metab. 2009 Mar;29(3):495-503. PubMed abstract

Seo Y, Hashimoto T, Nuki Y, Hasegawa BH. In vivo microCT imaging of rodent cerebral vasculature. Phys Med Biol. 2008 Apr 7;53(7):N99-107. PubMed abstrac

Hashimoto T, Meng H, Young WL. Intracranial aneurysms: links among inflammation, hemodynamics and vascular remodeling. Neurol Res. 2006 Jun;28(4):372-80. Review. PubMed abstract

Shimada K, Furukawa H, Wada K, Korai M, Wei Y, Tada Y, Kuwabara A, Shikata F, Kitazato KT, Nagahiro S, Lawton MT, Hashimoto T. Protective Role of Peroxisome Proliferator-Activated Receptor-? in the Development of Intracranial Aneurysm Rupture. Stroke. 2015 Jun; 46(6):1664-72. PMID: 25931465; PMCID: PMC4447500

Makino H, Hokamura K, Natsume T, Kimura T, Kamio Y, Magata Y, Namba H, Katoh T, Sato S, Hashimoto T, Umemura K. Successful serial imaging of the mouse cerebral arteries using conventional 3-T magnetic resonance imaging. J Cereb Blood Flow Metab. 2015 Sep; 35(9):1523-7. PMID: 25920958; PMCID: PMC4640342

Shimada K, Furukawa H, Wada K, Wei Y, Tada Y, Kuwabara A, Shikata F, Kanematsu Y, Lawton MT, Kitazato KT, Nagahiro S, Hashimoto T. Angiotensin-(1-7) protects against the development of aneurysmal subarachnoid hemorrhage in mice. J Cereb Blood Flow Metab. 2015 Jul; 35(7):1163-8. PMID: 25757758; PMCID: PMC4640268

Tada Y, Makino H, Furukawa H, Shimada K, Wada K, Liang EI, Murakami S, Kudo M, Kung DK, Hasan DM, Kitazato KT, Nagahiro S, Lawton MT, Hashimoto T. Roles of estrogen in the formation of intracranial aneurysms in ovariectomized female mice. Neurosurgery. 2014 Dec; 75(6):690-5; discussion 695. PMID: 25181430; PMCID: PMC4399640.

Tada Y, Wada K, Shimada K, Makino H, Liang EI, Murakami S, Kudo M, Shikata F, Pena Silva RA, Kitazato KT, Hasan DM, Kanematsu Y, Nagahiro S, Hashimoto T. Estrogen protects against intracranial aneurysm rupture in ovariectomized mice. Hypertension. 2014 Jun; 63(6):1339-44. PMID: 24732889; PMCID: PMC4034536.

Contact Us

Contact Information

Hashimoto Lab
ZSFG Anesthesia
1001 Potrero Avenue, Room 3C-38
San Francisco, CA 94110
tel: 415-206-8958
fax: 415-206-8170

Shipping Address:
Zuckerberg San Francisco General
1001 Potrero Avenue
Building 1 Room 150
San Francisco, CA 94110
Map of San Francisco General Hospital.