Title Associate Professor of Radiation Oncology Institution Massachusetts General Hospital Department Radiation Oncology Address Massachusetts General Hospital Dept. of Radiation Oncology, Cox 7 100 Blossom Street Boston MA 02114
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Biography
2010
Martin Research Prize for Excellence in Clinical Research
2011
NIH Director's New Innovator Award
Overview
As part of the Edwin L. Steele Laboratories for Tumor Biology, the Padera Laboratory examines the function of lymphatic vessels in health and disease, with an emphasis on the pathophysiology of tumor associated lymphatic vessels and lymphatic metastasis. Lymphatic vessels are responsible for draining interstitial fluid from tissues and for transporting immune cells to lymph nodes to maintain the body's immune surveillance. Lymphatic vessels also facilitate the dissemination of cancer cells from a primary tumor to regional lymph nodes. The mechanisms used by cancer cells to form lymph node metastasis are starting to be understood, with the hope of identifying treatment strategies to lower mortality due to disseminated cancer. In contrast to hematogenous metastasis, in which the primary tumor has functional blood vessels for cancer cells to invade, the story for lymphatic metastasis is likely more complicated as solid tumors seem to lack functional intratumor lymphatic vessels. Functional lymphatic vessels in the margin of tumors, however, seem sufficient for lymphatic metastasis to occur.
Using intravital microscopy, we have investigated the individual steps of lymphatic metastasis. We can monitor lymphatic vessels in the tumor margin, observe tumor cells moving in lymphatic vessels, measure lymph flow and quantify the number of tumor cells that arrive in the draining lymph node. Our studies have shown that VEGF-C, which is associated with lymphatic metastasis in patients, increases the size of the tumor margin lymphatic vessels, making them more vulnerable to invasion. Our data suggests that VEGF-C needs to be blocked very early in the metastatic process to be able to reduce VEGF-C enhanced lymphatic metastasis.
In addition to our work on metastasis, we have studied the molecular mechanisms that regulate the autonomous lymphatic contractions that drive lymph flow. Using novel animal models and intravital microscopy, we have shown that normal lymphatic contractions are reliant upon nitric oxide that is produced in specific locations at specific times. When the spatial and temporal control is lost during inflammation, the contractions stop and lymph function is impaired.
Our future studies will continue to dissect the physical and molecular determinants of lymphatic vessel function and lymphangiogenesis in both normal and disease states. In addition we will continue to understand the mechanisms of cancer dissemination through lymphatic vessels and subsequent growth in lymph nodes. Through the use of our novel imaging technologies and animal models, we will answer timely questions that can lead to the development of treatments for lymphatic metastasis and lymphedema.
Research
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R01CA284603
(PADERA, TIMOTHY P)
Jul 1, 2023 - Jun 30, 2028
Systems Biology of Antigen and T-Cell Transport in Cancer Immunotherapy
Role: Principal Investigator
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R01CA284372
(PADERA, TIMOTHY P)
Jun 1, 2023 - May 31, 2028
Targeting lymph node metastases to block cancer progression
Role: Principal Investigator
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R21AI135092
(PADERA, TIMOTHY P)
Jun 1, 2018 - May 31, 2020
Mechanism of methicillin-resistant Staphylococcus aureus induced lymphatic dysfunction
Role: Principal Investigator
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R01CA214913
(PADERA, TIMOTHY P)
Mar 2, 2017 - Jan 31, 2023
Targeting lymph node metastases to prevent cancer progression
Role: Principal Investigator
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R01HL128168
(MUNN, LANCE L)
Aug 1, 2015 - Nov 30, 2020
Systems biology of lymphatic transport
Role: Co-Principal Investigator
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R21AI097745
(PADERA, TIMOTHY P)
Feb 15, 2012 - Jan 31, 2015
Characterization of lymphatic contraction during infection
Role: Principal Investigator
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DP2OD008780
(PADERA, TIMOTHY P.)
Sep 30, 2011 - Jun 30, 2016
Characterizing lymphatic micrometastases: prognostic and therapeutic implications
Role: Principal Investigator
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R00CA137167
(PADERA, TIMOTHY P)
Sep 12, 2008 - Aug 31, 2014
Role: Principal Investigator
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K99CA137167
(PADERA, TIMOTHY P.)
Sep 12, 2008 - Aug 31, 2011
Role: Principal Investigator
Bibliographic
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