Kazuaki Takabe

Kazuaki Takabe

MD, PhD, FACS

Specializing In:

Breast cancer

About Me

Biography:

Breast cancer is a common disease that one out of eight women in this country will be told they have during their lifetime. Thanks to the advance in breast cancer detection and management, the overall survival has improved up to approximately 90 percent five years after it is found. Yet, we still lose 40,000 women every year in the United States to this disease. This seemingly conflicting fact is not only because there are many breast cancer patients, but also because it can come back 10 or 15 years down the line.

Our mission is to support for the long term survival of breast cancer and enable our patients to live longer and happier. Here at Roswell Park Comprehensive Cancer Center, breast surgeons, radiologists, medical and radiation oncologists, plastic surgeons, pathologists, and psychologists all work together as a multidisciplinary team to manage your breast cancer. In a vast majority of the cases, breast cancer does not come back at the site we remove it from. Instead, it can show up in the bones, liver, lung, or brain. This is why it is so important that a surgeon — who removes cancer from the breast — and the whole multidisciplinary team need work together to fight breast cancer.

I am a surgical oncologist dedicated to helping breast cancer patients with surgical treatment. I was trained in general surgery at the University of California, San Diego as well as in Japan. After the completion of specialized training in surgical oncology following residency, I continued as an attending surgical oncologist and a faculty member for a decade at the Medical College of Virginia Hospital at Virginia Commonwealth University School of Medicine prior to my arrival to Roswell Park. In my clinical practice, I place a high value in the patient’s satisfaction.

In addition to my extensive surgical career, I was awarded a PhD, followed by postdoctoral training at the Salk Institute in La Jolla, California. I am a Principal Investigator with a laboratory funded by multiple NIH-R01 grants and a Susan G. Komen Foundation grant. With my unique background as a surgeon-scientist, my vision is to translate the latest discoveries from the Roswell Park laboratories to patients whose cancer cannot be controlled by the standard treatments.


Credentials

Positions

Roswell Park Comprehensive Cancer Center
  • Professor of Oncology
  • Clinical Chief of Breast Surgery
  • The Alfiero Foundation Endowed Chair in Breast Oncology
  • Breast Program Leader
  • Breast Disease Site Leader
  • Breast Oncology Fellowship Program Director
Jacobs School of Medicine and Biomedical Sciences, University at Buffalo
  • Professor of Surgery
  • Division of Surgical Oncology
  • Department of Surgery
Tokyo Medical University
  • Visiting Professor

Background

Education and Training:

  • 1999 – PhD – Yokohama City University Graduate School of Medicine, Yokohama, Japan
  • 1992 – MD – Niigata University School of Medicine, Niigata, Japan

Residency:

  • 2006 – Department of Surgery – University of California San Diego, San Diego, CA
  • 1995 – Department of Surgery – Niigata University Hospital, Niigata, Japan

Fellowship:

  • 2008 – Surgical Oncology – Virginia Commonwealth University, Richmond, VA

Board Certification:

  • 2010 – Fellow of American College of Surgeons
  • 2007 – American Board of Surgery

Professional Memberships:

  • 2014 - Southern Surgical Association
  • 2014 - Society of University Surgeons (Publication Committee Member)
  • 2013 - Surgical Biology Club
  • 2010 - American Society of Breast Surgeons (#10789)
  • 2009 - American Society of Breast Disease (Member)
  • 2008 - American Association for the Advancement of Science (#202391312)
  • 2008 - Association for Academic Surgery (Publication Committee Member)
  • 2007 - Society of Surgical Oncology (Member #101619)
  • 2007 - American Society of Clinical Oncology (Membership Committee Member #77856)
  • 2007 - Japanese Medical Society of America (Active Member)
  • 2007 - American Association for Cancer Research (Member #141397)
  • 2006 - American Medical Association (Member ME# 57215920013)
  • 2005 - The Society of American Gastrointestinal and Endoscopic Surgeons (Member #763-23-793)
  • 2003 - American College of Surgeons (Member #03071672)
  • 1998 - International Association of Surgeons, Gastroenterologists and Oncologists (Permanent Faculty)
  • 1993 - Japan Surgical Society
  • 1993 – Japan Gastrointestinal Surgery Society

Professional Experience:

  • 2013-2016 - Associate Professor of Surgery, with joint faculty appointment in Biochemistry & Molecular Biology, Virginia Commonwealth University (VCU)
  • 2008-2013 - Assistant Professor of Surgery, with joint faculty appointment in Biochemistry & Molecular Biology, VCU

Honors & Awards

  • 2016 - Visiting Professorship, Tokyo Medical University, Shinjuku Japan
  • 2015 - Outstanding Speaker, Cancer Biology, VCU Biology Department
  • 2014 - Scholarship for 2014 Geisel Leadership Course at Dartmouth
  • 2012 - First Place - Clinical & Translational Research Category, Women’s Health & Sex Difference Research Scientific Poster Session, Women’s Health 2012: The 20th Annual Congress, National Institute of Health (NIH) Office of Research on Women’s Health
  • 2011 - Patients’ Choice Award, MDx Medical Inc, NJ
  • 2009 - Patients’ Choice award, MDx Medical Inc, NJ
  • 2007 - One of America’s Top Surgeons, Consumers’ Research Council of America
  • 2007 - First Prize Winner of Resident Paper Competition, Virginia Chapter of American College of Surgeons
  • 2006 - First Prize Winner of Resident Paper Competition, Virginia Chapter of American College of Surgeons
  • 2005 - 9th Yujin Memorial Young Investigator Award, Niigata University School of Medicine, Japan
  • 2004 - Surgical Forum Presenter, American College of Surgeons 90th Annual Clinical Congress
  • 2003 - Surgical Forum Presenter, American College of Surgeons 89th Annual Clinical Congress
  • 2003 - Third Prize, 342th Sankei Paper Competition “My Medical Reform”
  • 2003 - Prize Winner, San Diego Chapter of American College of Surgeons, Paper Competition
  • 2002 - First Prize Winner, San Diego Society of General Surgeons Resident Paper Competition
  • 2002 - Who’s Who in America
  • 1999 - President’s Choice Poster Presentation, 50th Annual Meeting American Association for the Study of Liver Disease
  • 1992 - Third prize, Fifth All Japan Medical Graduate Manuscript Contest

Research

Research Overview:

Our laboratory focuses on three main themes:

1) The role of sphingosine-1-phosphate (S1P) in cancer progression

2) Development of animal models that mimic human cancer progression

3) The role of bile acid signaling in cell metabolism and cancer

S1P is a signaling lipid mediator, which is generated inside the cells by sphingosine kinases, exported out of the cells, then bind and signal through five S1P specific G-protein coupled receptors (S1PR1-5), coined “inside-out signaling’ (Takabe K et al, Pharmacological Reviews 2008, Takabe K et al, Journal of Lipid Research 2014). Given that S1P cause cell survival, proliferation, migration and angiogenesis, we hypothesized that S1P play critical roles in cancer progression. We found that S1P is exported via multidrug resistant protein, ABC transporter C1 and G2, which implicate that those transporters resist to drugs not only because they secrete out drug compounds, but also export S1P that biologically worsen cancer cells (Takabe K et al, Journal of Biological Chemistry 2010). We found that Spinster 2 also exports S1P and regulates lymphatic network development in the lymph nodes (Nagahashi M et al, FASEB Journal 2013) and play critical roles in inflammatory diseases (Donoviel MS et al, FASEB Journal 2015). These findings led us to investigate the roles of S1P in tumor microenvironment, and found that S1P promote not only angiogenesis, but also lymphangiogenesis and lymph node metastasis of breast cancer (Nagahashi M et al, Cancer Research 2012). We also found that S1P levels are high in breast cancer compared from the surrounding normal breast tissue (Nagahashi M et al, Journal of Surgical Research 2016) that associate with sphingosine kinase 1 activity of human breast cancer (Tsuchida J et al, Journal of Surgical Research 2016). We invented a method that identified that S1P levels are high not only in breast cancer cells, but also in interstitial fluid that forms tumor microenvironment (Nagahashi M et al, Journal of Mammary Gland Biology and Neoplasia 2016). We found that another ABC transporter, C11, export S1P and are associated with worse survival (Yamada A et al, Breast Cancer Research and Treatment 2013). Further, we discovered that S1P link inflammation and caner in colitis-associated colon cancer model (Liang J et al, Cancer Cell 2013). We also found that S1P phosphatase 2 promotes disruption of colonic mucosal integrity in inflammatory bowel disease (Huang WC et al, FASEB Journal 2016). In breast cancer, we found that obesity worsen breast cancer via S1P production (Hait NC et al, Oncogenesis 2015). Intracellularly, we found that LPA1 upregulate sphingosine kinase 1 (Shida D et al, Cancer Research 2008) via ERK1-dependent manner (Ramachandran S et al, FEBS Letter 2010), and S1P play an essential role in IL-1 induced CXCL10 and CCL5 production (Harikumar KB et al, Nature Immunology 2014).

We have established a technique to generate syngeneic murine metastatic breast cancer model that mimic human breast cancer progression (Rashid OM et al, Breast Cancer Research and Treatment 2014). Utilizing this model, we found that the benefit of removal of the primary breast cancer in Stage IV disease depend upon the tumor burden (Rashid OM et al, Surgery 2013), and we also found that the lung metastasis model by tail vein injection of cancer cells is genetically similar to lung metastasis tumor from breast tumor (Rashid OM et al, Journal of Thoracic Disease 2013). Further, we have improved this model to be used for testing immunotherapy (Katsuta E et al, Journal of Surgical Research 2016). We also developed a syngeneic murine metastatic colon cancer model that metastasizes to lymph node before causing bowel obstruction or carcinomatosis (Terracina KP et al Journal of Surgical Research 2015).

We found that conjugated bile acids bind to S1P Receptor 2 (S1PR2) and signal through ERK (Studer E et al, Hepatology 2012). We further discovered that this bile acid signaling through S1PR2 and Sphingosine kinase 2 regulate lipid metabolism in hepatocytes (Nagahashi M et al, Hepatology 2015), thus play a role in development of Non-Alcoholic Fatty Liver Disease (Hylemon P et al, Hepatology 2016).


Publications

Nagahashi M, Ramachandran S, Kim EY, Allegood JC, Rashid OM, Yamada, A, Zhao R, Milstien S, Zhou H, Spiegel S, and Takabe K. Sphingosine-1-phosphate Produced by Sphingosine Kinase 1 Promotes Breast Cancer Progression by Stimulating Angiogenesis and Lymphangiogenesis. Cancer Research 2012 Feb 1; 72(3):726-35.

Liang J, Nagahashi M, Kim EY, Yamada A, Huang WC, Hait NC, Harikumar KB, Allegood JC, Price MM, Avni D, Takabe K, Kordula T, Milstien S, and Spiegel S. Sphingosine-1-Phosphate Links Persistent STAT3 Activation, Chronic Intestinal Inflammation, and Development of Colitis-associated Cancer. Cancer Cell 2013; Jan 14; 23: 107-120.

Rashid OM, Nagahashi M, Ramachandran S, Yamada A, Graham L, Milstien S, Spiegel S, Bear HD, Takabe K. Resection of the Primary Tumor Improves Survival in Metastatic Breast Cancer by Reduction of Overall Tumor Burden. Surgery 2013 153(6): 771-778

Rashid OM, Nagahashi M, Ramachandran S, Dumur C, Schaum J, Yamada A, Terracina KP, Milstien S, Spiegel S, and Takabe K. An Improved Syngeneic Orthotopic Murine Model of Human Breast Cancer Progression Breast Cancer Research and Treatment 2014 Oct; 147(3):501-12.

Nagahashi M, Takabe K, Liu R, Wang Y, Hait NC, Wang X, Allegood JC, Yamada A, Aoyagi T, Liang J, Pandak WM, Cooper P, Spiegel S, Hylemon PB, and Zhou H. Conjugated Bile Acid Activated S1P Receptor 2 Is a Key Regulator of Sphingosine Kinase 2 and Hepatic Gene Expression. Hepatology 2015 Apr; 61(4):1216-26.