Research in the Colson Laboratory focuses on surgical innovation and surgical oncology, with NIH funding to study several novel approaches to cancer therapy with prior expertise in transplantation immunology and immune recognition.
Yolonda Colson, MD, PhD Chief, Division of Thoracic Surgery, Massachusetts General Hospital Hermes C. Grillo Professor of Surgery in the Field of Thoracic Surgery
Explore This Lab
About the Lab
The Colson Laboratory research team, led by Yolonda Colson, MD, PhD, in the Division of Thoracic Surgery at Massachusetts General Hospital, facilitates collaborations within thoracic surgery, immunology and engineering to improve the care of patients with cancer. Cross-disciplinary collaboration and synergy is central to the laboratory. The lab’s research interests are focused predominantly on surgical innovation and surgical oncology, with NIH funding to study several novel approaches to cancer therapy with prior expertise in transplantation immunology and immune recognition.
Dr. Colson is currently focused on addressing and preventing two problems surrounding lung cancer:
Local cancer recurrence
Lymph node recurrence and missed disease
Locoregional recurrence negatively effects a person’s quality of life as well as their long-term survival. For patients with an isolated, resectable local recurrence, surgery is the only potential remedial option. Unfortunately, for patients who have already underwent complete resection and are facing locally recurrent disease, current oncologic treatment remains inferior. There is a need for additional therapeutic options for patients with recurrence.
To combat recurrence, the Colson Laboratory is investigating new and emerging treatment modalities, such as polymer films and nanoparticles. These treatments have been identified as potential solutions for both prevention and treatment of locally recurrent cancers. The lab’s researchers expanded to using patient-derived xenograft models to test various chemotherapy drugs, antibody conjugates and polymer films to personalize cancer treatment and prevent recurrence.
The lab is focusing on near-infrared intra-operative sentinel lymph node imaging in patients with lung cancer and in the application of new compounds and drug delivery technologies to prevent cancer recurrence and metastasis. These clinical interests and projects have expanded the research, leading to multiple collaborative manuscripts in:
Targeting of locoregional malignant disease
Polymer-mediated drug delivery using flexible drug-eluting films, meshes and polymer nanoparticles
The lab has built significant expertise in assessing large and small animals in vivo, including models to assess treatment responses in human lung cancer, breast cancer, sarcoma and mesothelioma—both as primary tumors and recurrence following surgical resection. In addition, the team is actively involved in several clinical trials involving new technologies and treatments and in the design of clinical devices with corporate sponsored research agreements.
Dr. Colson’s clinical interest in surgical oncology and innovative treatment strategies has led to multiple collaborative manuscripts in lymphatic mapping, targeting of locoregional malignant disease, the prevention of post-surgical recurrence through both polymer film and nanoparticle technologies, and the intra-operative utility of novel infrared imaging.
Below are the Colson Laboratory's current projects funded by the National Cancer Institute (NCI) and NIH:
Efficacy and Safety of a Novel, Implantable Drug-eluting Film in Sarcoma
Grant: NIH, R01EB017722
Description: Development and large animal safety testing of chemotherapy-eluting biodegradable and biocompatible polymer films for local delivery of anti-neoplastic agents to treat retroperitoneal, abdominal, and pelvic sarcomas following surgical resection.
Tumor Specific Delivery of Verticillin A Overcomes Epigenetic Silencing Responsible for Drug Resistance
Grant: NCI, R01CA2227433
Description: This project seeks to co-deliver a variety of chemotherapeutic agents and the novel epigenetic agent Verticillin A, to overcome drug resistance, via a unique materials-based tumor-targeting nanoparticle delivery system. Anti-tumor efficacy of these pH-responsive nanoparticles will be evaluated in drug resistant tumors in vitro and in vivo, including PDX tumor models.
Suprahydrophobic Dual Drug Buttresses for Prevention of Lung Tumor Recurrence
Grant: NCI, R01CA232708
Description: Evaluation of new superhydrophobic buttress dual-loaded with paclitaxel and cisplatin to afford a controlled, sustained release of clinically relevant hydrophobic-hydrophilic drug combination with the goal of decreasing locoregional recurrence in non-small cell lung cancer patient-derived xenografts.
Optimization of Nanoparticle Tumor-Localization and Drug-Loading for Treating Mesothelioma
Grant: NCI, R01CA232056
Description: Evaluation of ultra-high drug-loaded nanoparticles employing a novel materials-based targeting approach. The aims are to:
Perform mechanistic studies to determine how chemical properties, nano-architecture and drug incorporation of PGC-PTX-eNPs impact functionality
Optimize formulation to maximize the anti-tumor effect against normal and drug-resistant mesothelioma cell lines and patient samples
Optimize formulation to determine biodistribution, PK, toxicity, PD/efficacy in a PDX model of mesothelioma
Below are the Colson Laboratory’s current projects related to industry:
Medical Robotics Project
Description: This collaboration involves strategic device design, market research and development of a new thoracic device.
Notable Contributions and Publications
*indicate publications by trainees while in the lab
Design and Validation of Drug-Eluting Polymer Films and Meshes for Peri-operative Locoregional Drug Delivery in Lung Cancer
Currently, the primary focus of the lab’s research is the development and testing of novel drug delivery platforms for administering chemotherapeutic agents in a controlled and targeted manner to prevent the locoregional recurrence of cancers following surgical resection, either locally at the suture line or within regional lymph nodes.
The lab has generated polymer films and superhydrophobic mesh constructs that are biocompatible and able to release high-dose chemotherapy agents in a controlled, sustained fashion. The superhydrophobic meshes maintain air at the solid-liquid interface; by varying the stability of the entrapped air layer within these 3D constructs, the rate of drug release is controlled.
The lab has generated polymers that effectively encapsulate several different chemotherapy drugs (i.e., SN-38, paclitaxel, cisplatin) and characterized subsequent time-, physical- and chemical-mediated release profiles. It was also the first to report the use of a stretch-induced, crack propagation mechanism to control drug release rates in superhydrophobic polymers. Polymer films and superhydrophobic meshes are amenable to both lipophilic and hydrophilic agents, suggesting potential widespread utility for several applications where tensile strain or device expansion are experienced, including in lung tissue. The lab has demonstrated in vivo efficacy in a murine model of lung cancer, colorectal cancer and sarcoma.
Design and Validation of Biologically Responsive Polymeric Nanoparticles for Drug Delivery to Tumor Bed and Lymph Nodes in Cancer
The lab has developed numerous polymer paclitaxel-loaded nanoparticles with pH-sensitive expansion and intracellular drug release mechanisms to decrease recurrence both locally and within regional lymph nodes following surgical resection. Its paclitaxel expansile nanoparticles (Pax eNPs) have shown significant decreases in tumor cell viability and local recurrence in a murine model for lung cancer, peritoneal malignant mesothelioma, pancreatic peritoneal carcinomatosis and ovarian cancer. Additionally, Pax eNPs significantly decreased nodal metastases in a murine breast cancer model.
The lab has also studied nanoparticle lymphatic migration and nodal targeting in a large animal model as well as real-time imaging of lymphatic migration within regional lymph nodes. It has developed hybrid polymer/lipid nanoparticles, which allow for the swelling behavior of expansile nanoparticles with improved colloidal stability and surface functionality, resulting in greater potency. Finally, it has recently developed a two-step drug delivery mechanism in Pax eNPs utilizing partition coefficient concepts, resulting in significantly higher local drug concentrations.
Characterization of Micrometastatic Nodal Disease Through the Real-Time Identification of Sentinel Lymph Nodes in Lung Cancer Patients Using Near-Infrared Imaging
An NCI-funded Phase I/II clinical trial in lung cancer explored the clinical application of an optical imaging technology that uses safe, invisible near-infrared (NIR) fluorescent light to permit SLN identification via real-time image guidance during surgery. Optimized NIR fluorescent lymphotropic contrast agents have been developed to permit nonradioactive real-time lymphatic mapping and the lab has enhanced and validated the technology in large animal models. Unique clinical aspects of lung cancer required fundamental changes in techniques and technology. The lab has now demonstrated that real-time image-guided detection and excision of the tumor-specific SLN using NIR fluorescent technology provides a safe and clinically applicable means to improve surgical staging with therapeutic benefit to patients with many types of cancer through first-in-human clinical trials in melanoma and lung cancer.
Dr. Colson provides academic mentoring and research training for surgical residents, post-doctoral fellows, motivated undergraduate and international visiting scholars. Her current and past resident research trainees include:
Jessica Copeland, MD
Project: The Role of Wearable Devices in Surgery to Predict and Detect Early Postoperative Complications
Institution: Mass General
Mehida Rojas-Alexandre, MD
Project: Efficacy and Safety of a novel, Implantable Drug-Eluting film in Sarcoma
Institution: Brigham and Women’s Hospital
William Blessing, PhD, post-doctoral fellow
Project: Gender-Based Differences in Lung Adenocarcinoma
Lillian Tsai, MD
Project: An Implantable Microdevice for Personalized Chemotherapy to Prevent Recurrence in Non-Small Cell Lung Cancer
Institution: Johns Hopkins Medicine
William Phillips, MD
Project: Lung Cancer Strategist Program
Institution: Northwestern University
Ngoc-Quynh T. Chu, MD
Project: Immunomodulation of Tumor-Draining Lymph Nodes for Prevention of Nodal Metastases in Non-Small Cell Lung Cancer
Institution: Beth Israel Deaconness Medical Center
David Mahvi, MD
Projects: Decreasing Local Recurrence with Paclitaxel-Eluting Films in Sarcoma and Medical Robotcs Project
Institution: Brigham and Women’s Hospital
Kathleen Weiss, MD
Projects: Clinical Trials in NIR Imaging and Microdevice Development for in vivo Chemotherapy Selection in Lung Cancer
Institutions: Brigham and Women’s Hospital and Beth Israel Deaconness Medical Center
Christopher Digesu, MD
Project: NIR Image-guided Lymphatic Mapping, Mechanisms of High Dose Paclitaxel in Paclitaxel-eluting Polymer films
Institution: Beth Israel Deaconness Medical Center
Iriny Ekladious, PhD, candidate for biomedical engineering
Thesis: Poly (1,2-glycerol carbonate)-graft-succinic acid-paclitaxel Conjugate Nanoparticles for the Tunable Delivery of Paclitaxel
Institution: Boston University
Julia Wang, PhD
Thesis: Mechanoresponsive Drug Delivery: Harnessing Forces for Controlled Release
Institution: Alivio Therapeutics
Sophie Hofferberth, MD
Project: Innovative Clinical Pathways in Lung Cancer
Institution: Brigham and Women’s Hospital
Awards and Scholarships
Recent awards and scholarships that Dr. Colson has helped trainees secure include:
ACS Resident Research Scholarship
Alternate for American College of Surgeons Resident Research Scholarships for 2017
Brigham Research Institute Microgrant Award
Finalist in Clowes Research Symposium
Lung Research Symposium Poster
NIH-Loan Repayment Program
STS Looking to the Future Scholarship
SUS Resident Research Scholar Award
Thoracic Surgery Foundation (TSF) Award
TSF Resident Award
TSF Southern Thoracic Surgical Association Resident Research Fellowship Award
Best Clinical Research Oral Presentation at the HMS Surgery Research Day (second place prize)
About Dr. Colson
A thoracic surgeon with extensive immunology and engineering research background, Yolonda Colson, MD, PhD, is the chief of the Division of Thoracic Surgery at Massachusetts General Hospital and a professor of surgery at Harvard Medical School. In addition to her cardiothoracic surgical training at Brigham and Women’s Hospital, her academic training includes:
Bachelor’s in biomedical engineering from Rensselaer Polytechnic Institute
Medical degree from Mayo Medical School
PhD and general surgery residency at the University of Pittsburgh
Dr. Colson is the recipient of the George H.A. Clowes, Jr. Research Career Development Award from the American College of Surgeons and the Edward M. Kennedy Award for Health Care Innovation from CIMIT and is an officer and exam chair for the American Board of Thoracic Surgery and the vice president for the American Association for Thoracic Surgery. She has a specific clinical interest in increasing and improving the identification and treatment of lung cancer, starting with early detection, minimally invasive surgical approaches and potential adjuvant therapies in the operating room, as well as follow-up care including patient education. She also has particular interest in understanding the unique differences of lung cancer in women.
She is co-inventor on three awarded patents and has received over 20 foundation grants and eight R29/R01 grants from the National Institutes of Health and National Cancer Institute. She has over 147 peer-reviewed publications highlighting her previous work in transplantation and her most recent investigations in sentinel lymph nodes in lung cancer and polymer-mediated drug delivery.
Level 7 near-infrared positive sentinel lymph node after navigational bronchoscopy-guided perilesional “tattoo” with indocyanine green.
Sentinel lymph node
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The Lung Cancer Forum, supported by the Division of Thoracic Surgery at Massachusetts General Hospital, is an initiative that brings medical experts together with the shared goal of furthering education, conversation and coordinated action around the topic of lung cancer.