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:
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:
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:
Dates: 2016-2019
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.
Dates: 2018-2023
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.
Dates: 2019-2024
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.
Dates: 2019-2024
Grant: NCI, R01CA232056
Description: Evaluation of ultra-high drug-loaded nanoparticles employing a novel materials-based targeting approach. The aims are to:
Below are the Colson Laboratory’s current projects related to industry:
Dates: 2018-2021
Description: This collaboration involves strategic device design, market research and development of a new thoracic device.
*indicate publications by trainees while in the lab
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.
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.
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:
Recent awards and scholarships that Dr. Colson has helped trainees secure include:
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:
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.
