Laboratory of Yolonda Colson, MD, PhD

Overview

The Colson Laboratory research team in the Division of Thoracic Surgery at Mass General Brigham, facilitates collaborations within thoracic surgery, immunology and engineering to improve the care of patients with cancer. Cross-disciplinary collaboration and synergy are central to the laboratory. The lab’s research interests are focused predominantly on surgical innovation and surgical oncology, with research projects focused in device development, therapeutic platforms, and investigations of cancer.

Research Projects

Device Development

Development of Robotic Bronchoscopy Prototype

In conjunction with industry partners Canon Medical Systems USA, Inc, the Colson laboratory is actively developing a novel robotic bronchoscopy prototype. Preliminary experiments in animal models and human cadaveric models have demonstrated improved reach within the tracheobronchial tree compared to conventional bronchoscopy which has the potential to translate into the improved diagnosis of thousands of lung cancers annually.

Therapeutic Platforms

Bispecific T Cell Engagers (BiTEs) Against Lung Cancers

Despite advancements in diagnosing lung cancer earlier, non-small cell lung cancer (NSCLC) has a poor survival rate, estimated at 25-30%. While resection is the standard of care for early-stage lung cancer, additional therapies are available including: chemotherapy, radiation, and immunotherapy. While these therapies improve outcomes, they are often limited by adverse side effects. More recently, targeted protein therapies including bispecific T cell engagers (BiTEs) have shown promise due to their ability to target specific proteins expressed on the surface of lung cancer cells (i.e. EGFR, HER2, etc). BiTEs function by binding to proteins on both cancer cells and the patient’s own immune cells (T cells), bringing them together to facilitate immune-mediated cancer cell death. However, BiTEs are currently limited by their short half-lives which require frequent administration, and the high doses needed for efficacy, which are associated with adverse secondary events. Our collaborators in the Grinstaff laboratory at Boston University recently discovered a modified saRNA which prolongs expression of encoded proteins. From this discovery, we are currently investigating saRNA encoded BiTEs against various NSCLC target antigens.

Synergistic Effect of miRNA and Chemotherapy for the Treatment of Lung Cancer

In collaboration with the Grinstaff laboratory at Boston University, this research focuses on investigating the synergistic effect of a novel micro-RNA added to standard chemotherapy in the treatment of lung cancer using in vivo small animal models. The long-term goal is to develop a formulation that will potentiate the effects of existing chemotherapies, which would allow to decrease the required dose for therapeutic effect, limiting side effects.

Novel Bioadhesives for Air leaks, Hollow-viscous and Solid Organ Injuries

This research focuses on investigating the role of a novel patch and glue bio-adhesive to treat pulmonary air leaks, hollow-viscous and solid organ injuries. We have teamed up with partner labs and are conducting pre-clinical ex-vivo and in-vivo testing of novel bioadhesives in several injury models. This project is a collaboration with the Grinstaff laboratory at Boston University and the Lee laboratory at Brigham and Women’s Hospital.

Local Activation of Engineered Logic-Gated CAR-T Therapies

Engineered CAR-T therapy has been shown to have tremendous benefits in the treatment of liquid tumors. However, solid tumors have a unique microenvironment that suppresses local immune function and challenges the potency of this technology. Additionally, systemic activation of these CAR-T cells has the potential to lead to graft-vs-host disease and unintended activation of the patient’s systemic immune system. The technologies that we are currently evaluating are addressing these challenges by activating these logic-gated engineered CAR-T cells only in the presence of a small molecule drug-eluting mesh device that is implanted at the site of the tumor. In collaboration with the Grinstaff laboratory, we are evaluating the targeting, safety, and efficacy of this system in multiple murine models.

Multi-Drug-Resistant Tumor Models

The overexpression of the MDR gene family has been documented to play a major role in the development of chemotherapeutic resistance to a wide range of established chemotherapies across a wide range of cancers. To better understand these mechanisms and to further validate the localized drug delivery and chemosensitization of many bioengineered delivery systems that our lab is currently evaluating, several cell lines have been transduced to overexpress the gene MDR1. These cell lines are being evaluated in murine models to ensure their growth characteristics are reflective of the original tumor models utilized in the lab.

Self-Amplifying RNA Project

Self-amplifying RNA is an engineered RNA that is capable of self-replication inside a host cell, which allows for the overexpression of up to 10kB of genetic material and translation into functional protein products within the targeted cell. This project focuses on the biodistribution, safety, and efficacy of several different self-amplifying RNA constructs that produce functional cytokines or other potentially therapeutic proteins in tumor-bearing mouse models via lipid nanoparticles delivered systemically. These saRNAs differ in the promoter region of the construct as well as the desired protein produced. In collaboration with the Grinstaff laboratory, we are using various tumor-bearing murine models to assess tumor-specific and prolonged over-expression of these novel technologies.

Investigation of Cancer

Genetic Origins of Lung Cancer in Women

This project investigates biological differences in lung cancer between women and men, with a particular focus on genetic and molecular mechanisms that may contribute to disease development and progression. By leveraging large-scale genomic datasets, we aim to identify sex-specific patterns in tumor biology, including differences in tumor suppressor gene alterations and downstream signaling pathways. Ultimately, this work seeks to better understand how sex influences lung cancer risk and behavior, with the goal of informing more precise and personalized approaches to diagnosis and treatment.

DIPNECH and Neuroendocrine Lung Disease

This research focuses on diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) and its relationship to pulmonary carcinoid tumors. We aim to better understand how these lesions develop and evolve over time by studying their underlying genetic and molecular features. Through integrated analyses of patient samples, this work seeks to clarify the biological connections between early neuroendocrine proliferations and more advanced tumors. The long-term goal is to improve classification, risk stratification, and clinical management of this rare and increasingly recognized spectrum of lung disease.

Bronchoalveolar Lavage Fluid (BALF) Extracellular Vesicles (EV) for Molecular Precision Diagnostics of Lung Cancer

Each year, 3.2 million people in the U.S. are diagnosed with pulmonary nodules (PNs) with >50% of these patients will have multiple PNs. While approximately 95% of these PNs are benign, such a distinction is challenging to make based on imaging alone and performing a biopsy on every PN with indeterminate features is prohibitive from a healthcare system perspective. There is an urgent unmet clinical need to develop less-invasive methods to effectively risk-stratify indeterminate PNs, particularly in patients with multiple PNs identified on LCS. In recent years, there has been an increased focus on less-invasive liquid-based detection of lung cancer. In conjunction with Dr. Hyungsoon Im’s laboratory at Massachusetts General Hospital, the Colson laboratory is investigating the diagnosis of multiple PNs through lesion-specific BALF EV profiling.

Aspartate Metabolism in the Tumor Microenvironment

In order to assess amino acid metabolic dependencies of hypoxic tumors, especially in the context of tumors that may remain following resection surgery, several knockdowns and partially resected tumor models have been established. We are assessing changes in aspartate metabolism that occur following partial tumor resection, factors that impact tumor re-establishment, and how these changes occur in the context of their tumor microenvironment. More specifically, we are assessing the uptake of aspartate and glutamate from the tumor microenvironment, where they can be found in excess, the catabolism of these amino acids, and how these metabolic shifts contribute to the generation of reactive oxygen species, hypoxia, and changes in pH. We are using these findings to inform which aspects of these metabolic pathways may be easily targeted and predict how exploiting these metabolic dependencies may impact residual tumor growth, angiogenesis, and the function of the local immune system.

Major Collaborators

Mark W. Grinstaff, PhD

Dr. Grinstaff is the Director of the NIH T32 Program in Translational Research in Biomaterials (TRB) and the Nanotechnology Innovation Center (BUnano) at Boston University. Dr. Grinstaff is an author or co-author on more than 425 peer-reviewed manuscripts (h-index > 100), given more than 400 oral presentations, and an inventor or co- inventor on more than 200 issued patents or pending applications. He is a co-founder of several companies that are commercializing his ideas, and he has several products being sold and used in the clinic. His current research activities involve the synthesis of new macromolecules and biomaterials, self-assembly chemistry, cartilage imaging, drug delivery, wound repair, and modified self-amplifying RNA.

Hyungsoon Im, PhD

Dr. Im is an Associate Professor in the Center for Systems Biology at the Mass General Research Institute. Dr. Im’s lab develops novel devices and applications using state-of the art nanoplasmonic and photonic sensors. They also develop new materials to expand the utility of these sensors. Dr. Im’s vision is to bridge the fields of engineering and medicine for next-generation diagnostic technologies. Specific research projects include: nanoplasmonic sensing, microholography, nanospectroscopy, and nanophotonics.

Yuhan Lee, PhD

Dr. Lee is an Assistant Professor at Havard Medical School and Brigham and Women’s Hospital. Through his Innovative Biomaterials Lab, Dr. Lee’s key focus is identifying clinical and therapeutic unmet needs and to find solutions through biomaterials approach. With his expertise in the synthesis and characterization of new materials, Dr. Lee has been developing novel biomaterials for medical adhesive, drug delivery/formulation, and tissue engineering.

Publications

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