Harvard Catalyst Profiles

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Rakesh K. Jain, Ph.D.

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Biography
1983 - 1984
Guggenheim Fellow
1992
Founding Fellow
2003
Elected to the Institute of Medicine (IOM)
2004
Elected to the National Academy of Engineering (NAE)
2008
Elected to the American Academy of Arts and Sciences
2009
Elected to the National Academy of Sciences (NAS)

Overview
My research goals are (i) to further mechanistic understanding of the vascular, interstitial and cellular barriers to the delivery and efficacy of molecular medicine in tumors, (ii) to develop and test new strategies to overcome these barriers for improving detection and treatment of tumors, and (iii) to translate these strategies from bench to bedside and in the process discover new biomarkers and new strategies to improve the outcome further. This tight integration between bench and bedside is a hallmark of my research.

My educational goals are to train basic scientists, bioengineers and physicians in the systems biology of cancer. I have had the good fortune of mentoring more than 150 doctoral and postdoctoral fellows from diverse backgrounds including engineering, mathematics, physics, chemistry, molecular and cellular biology, immunology, pathology, radiology, radiation, medical and surgical oncology – listed in the Table in the next section. I have also had productive collaborations with a similar number of basic scientists and clinicians from Harvard, MIT and elsewhere. Findings from these collaborative efforts are summarized in more than 525 publications, seven monographs and six patents.

For highlights of our key research findings, please visit: http://steele.mgh.harvard.edu

Mentoring
Available: 10/24/18, Expires: 12/31/25

The overall goal of our research is to understand the role of the tumor microenvironment 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. The tumor microenvironment includes the tumor vasculature, the stromal compartment such as cancer-associated fibroblasts, extracellular matrix and immune cells, and also the lymphatic vasculature.

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 for tailoring individual therapies.

Our lab has also shown that the dense extracellular matrix of tumors leads to high mechanical forces known as solid stress within tumors. This solid stress compresses/collapses blood vessels in the tumor, leading to poor delivery of conventional therapeutics. We have shown that the use of losartan, an angiotensin receptor blocker (ARB) commonly used to treat high blood pressure, can reduce extracellular matrix in tumors, leading to decreased solid stress within tumors, decompressing blood vessels and improving drug delivery.

This preclinical work has led to a clinical trial at MGH where losartan is given to patients with pancreatic ductal adenocarcinoma (PDAC) together with conventional chemotherapy, and it has been shown that losartan increases the R0 resection rate in resectable and borderline resectable PDAC patients. Other projects in the lab include reprogramming the immune microenvironment of tumors to improve the efficacy of immunomodulatory drugs such as immune checkpoint blockers; lymphatic function and lymphangiogenesis; dissection of steps in 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.

Simultaneous Measurements of pO2 and pH in Living Tumors with Three-Dimensional Resolution by Multiphoton Laser-scanning Microscopy
Summer, 06/16/02 - 08/10/02
In vitro Quantification of Metastic Tumor Cell Migration
Summer, 06/23/99 - 08/31/99
Tumor vessel normalization effects of MMP-14 inhibition
Summer, 05/20/10 - 08/31/10
Search for the Mechanism of Resistance of HER2-positive Breast Cancer Brain Metastases to Targeted Therapies
Summer, 06/11/12 - 07/31/12

Research
The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
  1. R01CA269672 (JAIN, RAKESH K.) Apr 1, 2022 - Mar 31, 2027
    NIH
    Reprogramming the tumormicroenvironment to improve immunotherapy of glioblastoma
    Role: Principal Investigator
  2. U01CA261842 (MUNN, LANCE L) Sep 22, 2021 - Aug 31, 2026
    NIH
    Targeting physical stress-driven mechanisms to overcome glioblastoma treatment resistance
    Role: Co-Principal Investigator
  3. R01CA259253 (JAIN, RAKESH K.) May 1, 2021 - Apr 30, 2026
    NIH
    Improving treatment of HER2+ breast cancer brain metastasis by targeting lipid metabolism
    Role: Principal Investigator
  4. U01CA224348 (JAIN, RAKESH K.) Sep 30, 2017 - Aug 31, 2022
    NIH
    Reprogramming PDAC tumor microenvironment to improve immunotherapy
    Role: Principal Investigator
  5. R01CA208205 (FUKUMURA, DAI) Jun 15, 2017 - May 31, 2022
    NIH
    Reengineering obesity-induced abnormal microenvironment to improve PDAC treatment
    Role: Co-Principal Investigator

Bibliographic
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.