Investigator: Rakesh Jain Institution: Massachusetts General Hospital (MGH)
Rakesh K. Jain is the Andrew Werk Cook Professor of Tumor Biology at Massachusetts General Hospital in the Harvard Medical School and Director of the E.L. Steele Laboratories for Tumor Biology at the Massachusetts General Hospital. He was among the top 1% cited researchers in Clinical Medicine in 2014-15. He is a member of editorial advisory boards of 22 journals, including Nature Reviews Cancer and Nature Reviews Clinical Oncology. He is a member of the American Academy of Arts and Sciences as well as all three branches of the US National Academies - the National Academy of Medicine, the National Academy of Engineering, and the National Academy of Sciences. In 2014, he was chosen as one of 50 Oncology Luminaries on the occasion of the 50th anniversary of the American Society of Clinical Oncology. In 2016, he was awarded the National Medal of Science.
Breast cancer remains the second leading cause of cancer-related death among women, which is primarily caused by metastatic disease, signaling a strong need for improved therapies for residual disease. However, the development of novel treatments is intrinsically limited by our inability to monitor the response of small metastatic lesions to treatment in vivo. We aim to address this unmet need through the use of novel infrared emissive quantum dot (QD) probes with which we will be able to monitor ultra-small cancer cell clusters in deep tissue.
Within the LBRC, Bawendi's Lab has recently focused on two main areas. First, the team has developed novel high quality QDs in the short-wavelength infrared (SWIR) region [1]. The indium-arsenide-based SWIR QDs are readily modifiable for various functional imaging applications, and exhibit narrow and size-tunable emission and a dramatically higher emission quantum yield than previously described SWIR probes. One of several applications for SWIR imaging with QDs is angiography of tumors to study angiogenesis (Fig. 1). Second, we have developed functional QDs for in vivo single cell imaging and in vivo cytometry [2]. The intense and stable fluorescent signal of QDs allows long-term tracking of single cells in intact or diseased tissues in vivo. Further, the approach can be extended to un-manipulated animals as opposed to genetically modified, immunodeficient, or preirradiated mice. In addition, LBRC has also recently demonstrated three-photon wide-field depth-resolved imaging using different chromophores including channelrhodopsins and quantum dots [3].
All the areas mentioned above are the focus of further research and development. Specifically, LBRC plans to continue improving our imaging technology in close collaboration with our collaborators at MGH. In particular, wide-field SWIR excitation two-photon microscopy is expected to improve the penetration depth and z-resolution drastically compared to our current instrumentation. As part of our probe development kit, we will develop improved SWIR probes combining high two-photon cross section with improved photostability for this collaboration.
The unmet need of monitoring ultra-small metastatic cancer cell cluster in deep tissue drives the need to develop novel infrared emissive probes with unprecedented contrast and penetration depth for fluorescence imaging. The technology development in TRD1 and TRD4 will help us reliably detect these metastatic cancer cell clusters, which is focus of this collaboration with the Jain lab aimed at monitoring tissue environments with metastatic cancer cell clusters.