Projects

Photodynamic Therapy

Photodynamic therapy uses light and photosensitizers to produce chemicals with short diffusion lengths and lifetimes that damage cancer cells on a local level, circumventing systemic toxicity in the patient.

Imaging and photodynamic therapy: mechanism, monitoring, and optimization.(Chem Rev 2010)

 The role of photodynamic therapy in overcoming cancer drug resistance.(Photochem Photobiol Sci 2015)

Using cellular mechanisms to develop effective combinations of photodynamic therapy and targeted therapies.(J Natl Compr Canc Netw. 2012)


Photodynamic Therapy Based Combination Therapies


The order and timing of the delivery of therapies are critical factors in the success or failure of a treatment regimen. In this project, we examine the reasons for this and develop methods to rapidly screen for optimal treatment strategies. 

Synergistic enhancement of carboplatin efficacy with photodynamic therapy in a three-dimensional model for micrometastatic ovarian cancer.(Cancer Res 2010)

Low-dose methotrexate enhances aminolevulinate-based photodynamic therapy in skin carcinoma cells in vitro and in vivo.(Clin Cancer Res 2009)


Photoimmunotherapy & Photoimmunoconjugates


By linking antiboides and photosensitizers, we are able to increase the specificity and decrease the systemic toxicity of our therapies. 

Selective treatment and monitoring of disseminated cancer micrometastases in vivo using dual-function, activatable immunoconjugates.(Proc Natl Acad Sci U S A 2014)

Vaccination with photodynamic therapy-treated macrophages induces highly suppressive T-regulatory cells.(Photodermatol Photoimunol Photomed 2011)

Targeting cells that overexpress the epidermal growth factor receptor with polyethylene glycolated BPD verteporfin photosensitizer immunoconjugates.(Photochem Photobiol 2003)


Nanotechnology


Multi-agent nano constructs allow for flexibility in designing therapeutic regimens to overcome a broad spectrum of systemic and microenvironmental barriers. We develop photo-responsive nanoconstructs that encapsulate a variety of theranostic agents and preferentially release them at the desired site through both enhanced accumulation and selective activation. Conjugating targeting moieties to liposomal nano constructs also provides a means for cancer cell-selective delivery of anti-tumor agents.

Impacting Pancreatic Cancer Therapy in Heterotypic in Vitro Organoids and in Vivo Tumors with Specificity-Tuned, NIR-Activable Photoimmunonanoconjugates: Towards Conquering Desmoplasia?(Nano Letters 2019).

A new nanoconstruct for epidermal growth factor receptor-targeted photo-immunotherapy of ovarian cancer.(Nanomedicine 2013)

Light-Controlled Delivery of Monoclonal Antibodies for Targeted Photoinactivation of Ki-67.(Mol Pharm 2015)


Longitudinal Photoacoustic & Ultrasound Imaging


We focus on optical imaging techniques for image-guided resection, image-guided dosimetry, and therapy monitoring. 

Prediction of tumor recurrence and therapy monitoring using ultrasound-guided photoacoustic imaging.(Theranostics 2015)

Shining light on the dark side of imaging: excited state absorption enhancement of a bis-styryl BODIPY photoacoustic contrast agent.(J Am Chem Soc 2014)


3-D Tumor Modeling


Monolayer cell cultures often lack the environmental cues that are integral to recreating accurate models of cancer in the lab. This project works to develop models that more accurately mimic the response of cancer in a native environment. 

Modulation of redox metabolism negates cancer-associated fibroblasts-induced treatment resistance in a heterotypic 3D culture platform of pancreatic cancer.(Biomaterials 2019).

PDT dose parameters impact tumoricidal durability and cell death pathways in a 3D ovarian cancer model.(Photochem Photobiol 2013)

A three-dimensional in vitro ovarian cancer coculture model using a high-throughput cell patterning platform.(Biotechnol J 2011)


Quantitative Fluorescence Imaging in 3D


With the ever increasing development and utilization of three-dimensional cell culture models, there also comes the need for a system of quantitative analysis methods. In the lab, we develop computational-based fluorescence image analysis to extract useful information from our 3D models. 

Comprehensive high-throughput image analysis for therapeutic efficacy of architecturally complex heterotypic organoids.(Sci Rep 2017).

An imaging-based platform for high-content, quantitative evaluation of therapeutic response in 3D tumour models.(Sci Rep 2014)


Microfluidic 3-D Cancer Models


This project aims to create experimental setups that more accurately model the development of cancer in the environmental conditions found in the human body. These setups provide insight into the mechanisms that drive changes in cancer, such as the epithelial-mesenchymal transition. 

Flow-induced Shear Stress Confers Resistance to Carboplatin in an Adherent Three-Dimensional Model for Ovarian Cancer: A Role for EGFR-Targeted Photoimmunotherapy Informed by Physical Stress.(Journal of Clincial Medicine 2020).

Flow induces epithelial-mesenchymal transition, cellular heterogeneity and biomarker modulation in 3D ovarian cancer nodules.(Proc Natl Acad Sci U S A 2013)


Rapid Portable Screening of Antibiotic Resistance


The inability to rapidly detect antibiotic resistance in resource-challenged locations poses a significant significant threat to patients and communities. This project develops new approaches to reduce the cost and increase the speed of antibiotic resistance detection.

Rapid, low-cost fluorescent assay of β-lactamase-derived antibiotic resistance and related antibiotic susceptibility. (J Biomed Opt 2014)

Rapid optical determination of β-lactamase and antibiotic activity. (BMC Microbiol 2014)