Photomedicine and Biophysical Microscopy of Cancer
Image Credit: Bryan Spring
Image Credit: Nima Davoudzadeh
The Spring Laboratory at Northeastern University bridges biophysics, biomedical optics and cancer biology to selectively target microscopic deposits of tumor cells left behind by standard therapies that limit our ability to cure many malignancies. Optical spectroscopic imaging and photophysics are applied to visualize and mop up this residual disease. The ultimate goal of the program is to reduce cancer recurrence and mortality by establishing new approaches for personalized medicine that address tumor heterogeneity, drug-resistance and molecular mechanisms of treatment escape.
Advanced-stage cancer patients are presently subjected to a grueling treatment regimen consisting of surgical tumor debulking and high-dose-intensity chemotherapy. These standard approaches frequently hit a wall due to dose-limiting toxicities as well as mechanisms of drug-resistance and treatment escape via cell signaling networks. To address these challenges, the group’s efforts focus on developments in photomedicine in concert with guidance from in vivo microscopy for the discovery of dynamic molecular mechanisms of treatment escape and for the rational design of therapeutic regimens that overcome resistance. In vivo imaging is used for microscopic-resolution “optical biopsy” to identify drug-resistant cancer cells and to monitor cell signaling events without the need for invasive surgeries and tissue biopsies that can miss smaller lesions. Near infrared light activation of molecular-targeted chromophores is applied to selectively damage drug-resistant cancer cells, to suppress mechanisms of treatment escape and to sensitize the tumor to systemic therapies—including chemotherapy and immunotherapy.
A major focus of the group is to develop multicolor microendoscopy and molecular-targeted agents for both imaging and therapy. The group builds new fluorescence microscopy tools (e.g., hyperspectral, lifetime-resolved and FRET imaging); develops real-time image computation software; designs and synthesizes molecular-targeted probes; and, develops mouse models of cancer when required.
July 22, 2022 - Rebecca Harman and team have just published a paper in Biomedical Optics Express introducing a spectral vector denoising algorithm that filters out noise without sacrificing spatial information by leveraging redundant observations of spectral signatures within images of complex biological samples. The algorithm applies an n-dimensional Chebyshev or Fourier transform to cluster pixels based on spectral similarity independent of pixel intensity or location, and a denoising convolution filter is then applied in this spectral space. This innovative new image computation algorithm decreases fluorescence signal decomposition error up to 70% without degrading spatial resolution. The open source algorithm will be released soon for free academic use and available at springlabnu.com/software. Congratulations to Rebecca Harman and team!
September 3, 2021 - Dr. Ryan Lang's two-photon excitation spectra (700 - 1300 nm) and finding of enhanced multiplexing depth and photostability using long-wavelength two-photon excitation spectral peaks has been published in Biomedical Optics Express. Congratulations to Ryan!
August 10, 2021 - Ten multidisciplinary research teams will receive a combined $1,150,000 in funding as part of the inaugural year of Scialog: Advancing BioImaging, a three-year initiative, supported by Research Corporation for Science Advancement (RCSA), the Chan Zuckerberg Initiative (CZI) and the Frederick Gardner Cottrell Foundation (FGCF), that aims to accelerate the development of the next generation of imaging technologies.
August 5, 2021 - Congratulations to Dr. Ryan Lang who successfully defended his doctoral dissertation "Multiplexed In Vivo Imaging and Analysis Methods for Optical Imaging Biopsy of Cancer." Ryan entered the group with recognition as being exceptionally strong in theoretical physics. He put his math skills to use to solve difficult problems in dynamic imaging of tumor spatial heterogeneity and immunoscore using microendoscopy, and he grew into a team leader in physics, microscopy, and cancer biology. Ryan led several challenging projects to completion drawing on creativity and deep dives in quantum chemistry and multiphoton microscopy. His productivity is reflected in his publication record—he has co-authored 8 papers published, under review, or to be submitted shortly during his graduate career.
March 26, 2021 - Congratulations to Sophia Renauld who will graduate this May with a degree in biomedical physics, and attend the Harvard-MIT MD PhD program starting this summer! Woohoo, Sophia! We are proud of you.
February 24, 2021 - Prof. Spring has been selected as a Scialog Fellow for Advancing BioImaging (ABI), a new initiative jointly sponsored by the Research Corporation for Science Advancement, The Chan-Zuckerberg Initiative, and the Fredrick Gardner Cottrell Foundation.
January 6, 2021 - Cellaria Inc has launched a blogspot featuring a video interview with Prof. Spring:
June 15, 2020 - The Spring Research Group condemns acts of police brutality against Black communities and the entrenched systemic racism that has for far too long facilitated these acts. As physicists and medical researchers, our work is not separated from racial injustice. Physics and medical science are historically and presently dominated by white faces and voices, and there is an urgent need to enhance and to encourage the accessibility of physics as a field to underrepresented groups. The Spring Group recognizes the history of prejudice and racism inextricable from medical research and science. Institutions, including our own Northeastern University and Department of Physics, could do much more to combat racism in academia and science, especially anti-Black racism. We recognize that our silence on these issues has made us complicit in upholding institutional policies that come up short in the fight against racism. We commit to advocating for physics departments, including our own, to take concrete steps to begin outreach and recruiting policies that will help strengthen the diversity of our physics community with the hope that our voices, among others, will help to dismantle systemic racism within our society.
We also want to provide some resources for allies looking to financially support anti-racist organizations and relief funds. This spreadsheet also has tabs with resources to educate yourself on racism and police brutality in the U.S., petitions to sign, and other ways to take action. These lists are by no means exhaustive, but hopefully provide a place to start. A couple highlighted places to donate to are the ACLU and the Ella Baker Center for Human Rights.
May 1, 2020 - Congratulations to Dr. Eric Kercher who successfully defended his doctoral dissertation "New Methods and Tools for Optimizing Precision Photomedicine Research." Eric is the Spring Lab's inaugural PhD student and graduate. Eric's publication record speaks for itself—he has co-authored 8 papers published and under review during his graduate training spanning photomedicine, cancer biology and new device development.
April 1, 2020 - The Spring Laboratory has been awarded a NIH-NCI R01 award (R01 CA226855, $3.2M) titled "Multiplexed and dynamically targeted photoimmunotherapy of heterogeneous, chemoresistant micrometastases guided by online in vivo optical imaging of cell-surface biomarkers".
June 28 to July 4, 2019 - The Spring Research Group presented at the International Photodynamic Association (IPA) World Congress 2019 in Boston. Congratulations to Eric, Arvind, and Ryan and all the poster award winners:
Eric Kercher — Poster of Excellence (Top 10) and Invited Slam Talk
Arvind Mohan — Poster of Excellence (Top 10) and Invited Slam Talk
Ryan Lang — Poster of Merit (Top 20)
June 6, 2019 - Congratulations to Eric Kercher who passed his preliminary thesis examination!
Photo: group dinner at Petit Robert Bistro to celebrate. Left to right: Liam Price, Becca Harman, Alejandro Olmos, Bryan Spring, Ryan Lang, and Eric Kercher.
Feb 1 to 5, 2019 - The Spring Research Group presented at Photonics West 2019 in San Franciscio.
Eric Kercher: Real-time GPU accelerated hyperspectral unmixing, Poster 10889-40
Ryan Lang: Micro-image mosaicking for video-rate multi-channel fluorescence microendoscopy, Contributed oral presentation 10854-40, Endoscopic Microscopy
Kai Zhang: Custom fabrication of a high-performance femtosecond fiber laser for multiphoton microscopy, Contributed oral presentation 10882-28, Multiphoton Microscopy in the Biomedical Sciences
Bryan Spring: Targeting drug-resistant glioblastoma stem cells using photodynamic therapy, Invited oral presentation 10860-3, Photodynamic Therapy
Sept 6, 2018 - Members of the Spring Lab present their work at the annual Smith Family Foundation Scientific Poster Session.
The Smith Family Awards Program for Excellence in Biomedical Research has awarded $32.8 million in grants to support 163 newly independent faculty over the past 26 years. Each investigator receives $300,000 over three years.
Professor Spring received this prestigious award in 2017 for his project entitled: "Peering into Cancer Stem Cell Niches to Guide Suppression of Multiple Signaling Loop Pathways"
Left to right: Kai Zhang, Eric Kercher, Ryan Lang, and Taresh Sharan.
Visit to Moffitt Cancer Center to explore a new collaboration among mathematical oncologists, biomedical physicists, and ovarian tumor immunologists. Left to right: Jose Conejo-Garcia, Bryan Spring, Heiko Enderling, and Bob Gatenby (May 15, 2018; Tampa).