BBS Faculty Member - Rakesh Jain

Rakesh Jain

Andrew Werk Cook Professor of Tumor Biology (Radiation Oncology)
Director, Edwin L. Steele Laboratory for Tumor Biology


Massachusetts General Hospital
100 Blossom Street, Cox 7
Boston, MA 02114
Tel: 617-726-4083
Fax: 617-724-1819
Email: jain@steele.mgh.harvard.edu
Lab Members: 16 postdoctoral fellows; 6 graduate students
Visit my lab page here.



The overall goal of our research is to understand the role of the tumor microenvironment, including the tumor vasculature, in tumor growth and response to therapy, to develop novel strategies to manipulate the tumor microenvironment, and to translate these strategies into improved cancer detection, prevention and treatment in humans.

To unravel the complex biology of tumors, we have developed an array of imaging technologies, mathematical models, and animal preparations. These include multiphoton microscopy and genetically engineered mice with surgically implanted transparent windows, which permit in vivo visualization of gene expression and function in tumors and their surrounding host stroma. This undertaking has provided powerful molecular, cellular, anatomical, and functional insights into the barriers to cancer treatment.

Our work has revealed that the abnormal vasculature in solid tumors often thwarts the effectiveness of both conventional and novel therapies. Our laboratory is known for a new hypothesis that antiangiogenic therapy can "normalize" the abnormal tumor vasculature and improve both the delivery and efficacy of therapeutics. We have validated this concept in mice and patients receiving antiangiogenic therapy and in the process, discovered potential biomarkers of tumor escape from these therapies. We have also discovered the molecular mechanisms of vascular normalization. Now we are exploring novel strategies to expand the window of normalization and seeking potential biomarkers for tailoring therapies to individuals.

We have translated this insight into the vascular biology of tumors to engineer long-lasting blood vessels using for regenerative medicine. Now we are exploring the use of iPS cells in engineering blood vessels. Other projects in the lab include manipulation of the extracellular matrix of tumors to improve the delivery of conventional and nano-medicine; lymphatic function and lymphangiogenesis; dissection of biology with hematologic and lymphatic metastasis; drug screening for treatment of metastasis; and translation of these findings to the clinic.

Our laboratory is truly multidisciplinary spanning expertise in molecular and cellular biology, physiology, bioengineering, optics, mathematics to radiation, medical and surgical oncology. A tight integration between bench and bedside guides our research.



Last Update: 8/22/2013



Publications

For a complete listing of publications click here.

 


 

Carmeliet P, Jain, R; Molecular Mechanisms and clinical applications; Nature 2011 May 19; 473(7347): 298-307.

Jain RK, Stylianopoulos T; Delivering nanomedicine to solid tumors; Nature Rev Clin Oncol 2010Nov.; 7(11); 653-64.

S. R. Plotkin, A. O. Stemmer-Rachamimov, F. G. Barker II, C. Halpin, T. P. Padera, A. Tyrell, A. G. Sorensen, R. K. Jain and E. di Tomaso, “Hearing improvement after bevacizumab in patients with neurofibromatosis 2,” The New England Journal of Medicine 2009; 361: 24-33.

Jain RK. Taming vessels to treat cancer. Scientific American 2008; 298: 56-63.

Batchelor TT, et al. AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 2007; 11: 83-95.

Jain RK. Normalization of the tumor vasculature: An emerging concept in anti-angiogenic therapy. Science 2005; 307:58-62

Winkler F, et al. Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: Role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell 2004; 6:553-562.



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