Conor L. Evans
Wellman Center for Photomedicine
tel: (617) 726-1089; fax: (617) 726-8566
My research goal is to develop in vitro and in vivo optical microscopy and spectroscopy platforms to detect and visualize microscopic metastatic disease, understand how these cancerous lesions evade therapy on the microscale, and design and apply new therapeutic regimens to overcome treatment resistance. Although much progress has been made in detecting and treating cancer, disseminated metastatic disease remains the leading cause of death in cancer patients. In ovarian cancer in particular, frustratingly little is known regarding how these deadly lesions respond to and eventually resist treatment in vivo due to their widespread nature, often sub-clinical sizes, and highly heterogeneous microenvironments. The lack of appropriate imaging tools to understand and overcome treatment resistance on the microscale in metastatic cancer in vivo is a major unmet need in both cancer research and therapeutics. By creating new imaging platforms to understand therapeutic response on the microscale, we are taking a bottom-up approach in cancer therapeutics to build a comprehensive picture of treatment response from the cellular level all the way up to the macroscopic lesion.
Our highly interdisciplinary research is a biophysical approach to cancer therapy, where we use and develop physical tools to build our understanding of the mechanisms that underlie the rise of therapeutically resistant cancer. To visualize the numerous contributing factors in treatment response, we are developing new microscale imaging platforms based on physical tools such as fluorescence, phosphorescence and vibrational spectroscopy and optical tools such as optical coherence tomography (OCT), hyperspectral imaging, multiphoton microscopy, and non-linear Raman microscopies. As biophysicists, we are already combining the new information gained from these tools with fundamental physics and chemistry concepts to design and apply better therapeutics to eliminate treatment resistant cell populations before they can form.
One of our core research directions is focused on visualizing and measuring the microscale, cell-to-cell oxygenation levels in metastatic cancer. Diffusion of O2 into tissue typically only allows for 150-200 µm of penetration, resulting in hypoxic and necrotic tumor regions. Hypoxia triggers an array of built-in cellular defense mechanisms, allowing hypoxic tumor cells to resist many potent chemotherapeutics as well as radiation and most photodynamic therapy regimens. Importantly, the distribution of hypoxia is highly heterogeneous on the microscale, leading to a complex and mostly unknown landscape of treatment response. As part of cross-disciplinary biophysics research supported by a New Innovator Award (DP2), we are developing new spectral-ratiometric molecular oxygen imaging probes that can penetrate deep into solid tissue. These probes contain both an oxygen invariant fluorophore and an oxygen-sensitive phosphor; by taking their ratio we can precisely correlate oxygen concentrations with therapeutic response. To take advantage of these new probes, we are developing new hyperspectral microscopy and video-rate microendoscopy platforms to visualize oxygen tension and therapeutic response in both in vitro 3D and murine models of metastatic ovarian cancer.
I am passionate about translating fundamental biophysical concepts into future clinical applications so that we can improve cancer survival rates and increase patient quality of life. Using our imaging tools to study ovarian cancer models, we have found that cells in the cores of tumor nodules are both hypoxic and acidic, allowing these cellular populations to resist therapeutic intervention. To target this critical population, we are developing and applying photodynamic therapy agents that not only hone into hypoxic environments, but also can impart substantial cytotoxicity even under complete anoxia. By taking advantage of the physics and chemistry behind radical-generating chromophores, we are using and developing compounds based on benzo[a]phenothiazinium dyes, and are pursuing animal experiments with the goal of bringing these compounds into human trials. In a different translational direction, we are applying our microscale imaging technologies to develop a high-throughput, high-content metastatic cancer therapeutic screening platform. Using OCT and hyperspectral microscopy, the goal of this project is to grow patient cell samples into 3D tumor nodules and screen these samples against numerous therapeutic agents, doses, and dose schedules to create optimal, personalized treatment regimens.
Murigkar, S., Evans, C. L., Xie, X. S. Anis, H. Rapid detection of waterborne pathogens using coherent anti-Stokes Raman scattering (CARS) microscopy. J. Micro. 2009; 233: 244-250.
Evans, C. L., Rizvi, I., Hasan, T., de Boer, J. F. In vitro Tumor Growth and Treatment Response Dynamics Visualized with Time-Lapse OCT Imaging. Opt Express. 2009; 17(11); 12076-12087.
Joo, C., Evans, C. L., Stepnac, T., Hasan, T., de Boer, J. F. Field-based dynamic light scattering for quantitative investigation of intracellular dynamics. Opt. Express. 2010; 18(3); 2858-2871.
Evans, C. L. and Xie, X. S. Coherent Anti-Stokes Raman Scattering Microscopy: Chemical Imaging for Biology and Medicine. Ann. Rev. Anal. Chem. 2008; 1;883.
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