FRANCO LAB
Why we are here!
Cancer
Cancer is not a single disease, but instead a group of more than a hundred different diseases. It is defined by abnormal growth by which cells no longer respond to the signals that tell them what to do. This often leads to uncontrolled growth and sometimes metastasis, or spread of these cells outside the organ of origin. The goal of therapy is to prevent cancer cells from growing uncontrollably by selectively killing the cancers cells and preventing them from spreading. Understanding the molecular and genetic regulation of cancer cells will help us develop better more targeted therapies and improve outcomes for patients.
Tumors
We used to think that tumors were just cancer cells growing uncontrollably, and if we killed the cancer cells we could cure the patient. Unfortunately, it is not that simple. A tumor is more like a whole new, dysfunctional organ that doesn’t respond normally to cues from the outside. Tumors, in addition to having cancer cells, have normal cells including blood vessels, fibroblasts, and immune cells that the cancer cells have hijacked for their own benefit. We have done pioneering work to define stromal cells that are present in thyroid tumors, and demonstrate how these cells can help the tumors progress. We are seeking ways to manipulate the tumor microenvironment as novel therapeutic approaches to treat thyroid cancer.
Patients
We believe all lab questions can and should be patient-centric. In the Franco lab we currently have a broad interest in understanding how cancer cells and normal cells communicate in the tumor. We want to understand how this changes as patients age, and how different normal cells are recruited to tumors between pediatric and adult thyroid cancer patients. We believe this work will have important implications in improving patient outcomes in thyroid cancer, and helping to personalize care to pediatric and adult patients. With a better understanding of both the physiology and pathophysiology of the thyroid gland we can improve patient care!
Current Projects
Image credit: Smalley and Smalley, Cancer Discovery, 2018
MAPK Activation in Thyroid Cancer
We know that different driver mutations, even if they all activate MAPK signaling, can lead to the development of different subtypes of thyroid cancer. We have a variety of mouse models and patient cell lines with different driving mutations that we use to ask & dissect how genetics impacts physiological remodeling.
The questions we pose & try to address include:
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How do different driver mutations recruit different stromal cells?
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How does collagen crosslinking change tumor cell activation?
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How do tumor cells with different driver mutations activate or inhibit immune cells?
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Why do the same mutations confer different risks in pediatric versus adult thyroid cancer?
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Can we re-differentiate tumor cells with targeted therapy?
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The Role of Aging in Thyroid Tumorigenesis:
In collaboration with the Thyroid Center at CHOP, we are investigating why pediatric thyroid cancers often present with larger, more aggressive tumors than adult tumors, while maintaining a very favorable prognosis.
The questions we pose & are trying to address include:
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Do adult and pediatric tumors have the same microenvironment?
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How does age impact response to therapy?
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Do physical cues in the microenvironment change aging?
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Does age change the responsiveness of tumor cells to stimuli?
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Identifying the genetic drivers in pediatric thyroid cancer:
We are dissecting the genetic and molecular events that drive pediatric thyroid cancer to identify novel therapeutic strategies to improve quality of life outcomes for pediatric patients.
The questions we pose & try to address include:
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Do pediatric and adult thyroid tumors have different driver mutations?
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Does age impact what mutations develop in a tumor?
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Can we develop curative therapies for pediatric patients with metastatic thyroid cancer?
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Can mutations in the KEAP1/NRF2 pathway drive thyroid tumor progression?
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Patient Centric Questions
Any question we ask in the laboratory can be patient-centric. Understanding how our treatments for cancer cells affect other normal cells can help us identify potential side effects and consequences for patients being treated with these drugs. Understanding patients experiences can help us design therapies that preserve quality of life. We collaborate with patient advocacy groups and cancer survivors in our own lab to ask questions important to patients.
The questions we pose & try to address include:
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What does long-term survivorship look like for survivors of pediatric thyroid cancer?
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Does age of diagnosis impact Quality of Life?
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How does age affect thyroid cancer development?
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What questions are we not asking that might impact patients?
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We collaborate with advocates and cancer survivors to determine what other questions we should be asking​
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