Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, United States.
Thomas D Shupe studies conditions related to liver cancer and liver diseases, particularly focusing on the biology of cancer stem cells and liver stem cells known as oval cells. He explores how different proteins, like granulocyte-colony stimulating factor (G-CSF), can promote liver repair and influence cancer cell behavior. His research aims to better understand the mechanisms driving liver cancer, including why certain cells are resistant to treatment, ultimately paving the way for more effective therapies for people suffering from liver-related conditions.
Key findings
In his 2009 study, Shupe established six cancer cell lines from liver tumors in rats, finding that hepatocyte growth factor (HGF) aids cancer cell survival and granulocyte-colony stimulating factor (G-CSF) enhances their growth and mobility.
His research on G-CSF also demonstrated that this factor significantly boosts the activity of oval cells, indicating improved liver repair mechanisms.
Shupe identified cancer stem cells (CSCs) as critical components in liver tumors, noting that they are responsible for most tumor growth and regrowth after failed treatments.
Frequently asked questions
Does Dr. Shupe study liver cancer?
Yes, Dr. Shupe conducts extensive research on liver cancer, focusing on cancer stem cells and how they contribute to tumor growth and resistance to treatment.
What treatments has Dr. Shupe researched?
Dr. Shupe has researched the effects of granulocyte-colony stimulating factor (G-CSF) on liver repair and cancer cell behavior, which may lead to new treatment strategies for liver diseases.
Is Dr. Shupe's work relevant to patients with liver disease?
Yes, his research on liver stem cells and cancer stem cells is relevant as it could lead to improved therapies for patients suffering from liver diseases and liver cancer.
Publications in plain English
A human airway-on-a-chip microphysiological system for modeling chlorine gas toxicity.
2026
Toxicological sciences : an official journal of the Society of Toxicology
Murphy SV, Rajan SAP, Lindert K, Young T, Jiao Y +39 more
Plain English Researchers created a model of human airways on a chip to study the effects of chlorine gas exposure, which is important because there isn't much clinical data on how chlorine harms the body. They tested different levels of chlorine and found how it affects the body's cells and tissues over time. This research helps us understand how to protect people from chlorine gas injuries and develop better treatments.
Who this helps: This helps patients exposed to chlorine gas and healthcare providers treating them.
3D Bioprinted Liver-on-a-Chip for Drug Cytotoxicity Screening.
2024
Tissue engineering. Part A
Huh J, Parra JPRLL, Copus JS, Kang HW, Bishop CE +6 more
Plain English This research focused on creating a 3D printed liver model to test how drugs can affect liver cells. The scientists found that their liver tissue model was able to keep over 80% of its cells alive for 14 days and could accurately show the harmful effects of a common pain reliever, acetaminophen, which reduced cell viability to under 40% within a week. This is important because it offers a new way to study how drugs impact human tissues, which could lead to safer medication development.
Who this helps: This benefits researchers and pharmaceutical companies looking to improve drug testing methods.
In Vitro Generation of Haploid Germ Cells from Human XY and XXY Immature Testes in a 3D Organoid System.
2024
Bioengineering (Basel, Switzerland)
Galdon G, Zarandi NP, Deebel NA, Zhang S, Cornett O +12 more
Plain English Researchers studied how to create sperm cells from testicular tissue taken from young boys with normal chromosomes (XY) and those with Klinefelter syndrome (XXY). They found that after three weeks in a special 3D culture, the testicular cells maintained their structure and produced testosterone, and they successfully identified haploid cells, which are crucial for fertility. This matters because it opens the door for potential new fertility treatments for boys who are at risk of infertility due to cancer treatments or genetic conditions.
Who this helps: This helps young cancer survivors and boys with Klinefelter syndrome.
Bioreactor design and validation for manufacturing strategies in tissue engineering.
2022
Bio-design and manufacturing
Lim D, Renteria ES, Sime DS, Ju YM, Kim JH +8 more
Plain English This research focuses on improving how we manufacture tissues in the lab for medical use. It examines the design of bioreactors—special containers that help grow tissue—so they closely mimic the conditions found in the human body. The study underscores the importance of real-time monitoring to ensure the tissues develop properly, which is crucial for their effectiveness when implanted.
Who this helps: This benefits patients requiring tissue repair or replacement.
Therapeutic effects of a small molecule agonist of the relaxin receptor ML290 in liver fibrosis.
2019
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Kaftanovskaya EM, Ng HH, Soula M, Rivas B, Myhr C +15 more
Plain English Researchers studied a new drug called ML290, which targets a receptor in the liver to treat liver fibrosis, a condition that can lead to severe liver damage. They found that ML290 significantly reduced harmful collagen levels and cell growth in liver tissue, suggesting it can help reverse fibrosis. This is important because liver fibrosis currently has few treatment options and can lead to serious health issues.
Who this helps: This helps patients with liver fibrosis.
Urothelium with barrier function differentiated from human urine-derived stem cells for potential use in urinary tract reconstruction.
2018
Stem cell research & therapy
Wan Q, Xiong G, Liu G, Shupe TD, Wei G +5 more
Plain English This study explored the possibility of creating a type of bladder lining, called urothelium, from stem cells found in urine instead of using cells from bladder biopsies, which are more invasive. Researchers tested different methods on urine-derived stem cells from six healthy adults and found that the best method resulted in cells that not only looked right but also functioned well, showing lower permeability and forming tight connections similar to natural urothelium. This development is important because it offers a less invasive way to generate tissue that can be used in repairing the urinary tract.
Who this helps: This helps patients needing urinary tract repairs and doctors looking for better treatment options.
Optical Tracking and Digital Quantification of Beating Behavior in Bioengineered Human Cardiac Organoids.
2017
Biosensors
Devarasetty M, Forsythe S, Shupe TD, Soker S, Bishop CE +2 more
Plain English This study focused on developing a new way to measure how bioengineered heart tissues, called cardiac organoids, beat over time. Researchers created a simple system that uses video footage to track the movements of these organoids and found that it can effectively quantify their beating behavior. This method is quick, inexpensive, and doesn’t harm the organoids, making it valuable for testing new drugs and understanding their effects on heart health.
Who this helps: Patients and doctors involved in drug testing and development.
Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform.
2017
Scientific reports
Skardal A, Murphy SV, Devarasetty M, Mead I, Kang HW +17 more
Plain English This study focused on creating a new mini model of human organs using a system that combines liver, heart, and lung tissues. The researchers found that the way these tissues interact is crucial for understanding how drugs work and their potential side effects—in particular, they observed that drug responses changed when multiple tissues were present together. This matters because it can lead to better testing of new drugs before they are given to people, potentially reducing harmful recalls.
Who this helps: This helps patients and doctors by improving drug safety and effectiveness.
A liver-on-a-chip platform with bioprinted hepatic spheroids.
2016
Biofabrication
Bhise NS, Manoharan V, Massa S, Tamayol A, Ghaderi M +11 more
Plain English Researchers created a "liver-on-a-chip" system that uses 3D human liver cells to test the effects of drugs on liver toxicity. They discovered that their system could accurately detect harmful effects caused by acetaminophen, finding toxic responses after exposure to a concentration of 15 mM, similar to results from animal studies. This new model can better predict how drugs affect human livers, which is important for improving safety in drug development.
Who this helps: This benefits researchers and pharmaceutical companies developing new medications.
Bioengineered transplantable porcine livers with re-endothelialized vasculature.
2015
Biomaterials
Ko IK, Peng L, Peloso A, Smith CJ, Dhal A +8 more
Plain English This study focused on creating bioengineered pig livers that can be transplanted for patients who need a liver. Researchers successfully developed a method to rebuild the blood vessel network in these livers, leading to healthy blood flow for up to 24 hours after transplanting them into pigs. This is significant because it shows that engineered livers could eventually provide an alternative to donor organs for people suffering from severe liver disease.
Who this helps: This helps patients with end-stage liver failure who are in need of a transplant.
Stiffness of hyaluronic acid gels containing liver extracellular matrix supports human hepatocyte function and alters cell morphology.
2015
Journal of the mechanical behavior of biomedical materials
Deegan DB, Zimmerman C, Skardal A, Atala A, Shupe TD
Plain English This study looked at how the stiffness of a gel made from hyaluronic acid, which simulates the liver environment, affects liver cells called hepatocytes. The researchers found that when the gel stiffness was at 1200 Pascal, the liver cells were most active and producing a key protein called albumin, though their behavior started to decline after seven days, particularly at a higher stiffness of 4600 Pascal. This is important because it shows that creating a supportive environment for liver cells can help them function better in lab settings, which is crucial for developing effective liver therapies.
Who this helps: This benefits researchers and doctors working on liver diseases and therapies.
Immunogenicity of decellularized porcine liver for bioengineered hepatic tissue.
2013
The American journal of pathology
Mirmalek-Sani SH, Sullivan DC, Zimmerman C, Shupe TD, Petersen BE
Plain English This study examined a method for creating a scaffold from pig livers that could potentially be used to grow new liver tissue for patients with liver disease. Researchers successfully removed all cellular material from the pig livers while preserving important structures, and found that these scaffolds did not trigger a significant immune response in rats over 28 days. This is important because it shows that these pig liver scaffolds could be used safely in future experiments to create replacement liver tissues for people in need.
Who this helps: This helps patients with liver disease seeking new treatment options.
Inhibition of Notch signaling affects hepatic oval cell response in rat model of 2AAF-PH.
2011
Hepatic medicine : evidence and research
Darwiche H, Oh SH, Steiger-Luther NC, Williams JM, Pintilie DG +2 more
Plain English This study looked at how a specific signaling pathway called Notch affects the liver's ability to heal itself after injury in rats. Researchers found that when Notch signaling was blocked, there was a delay in the liver cells' ability to mature properly, which could lead to impaired liver function. Specifically, while the oval cells were activated and responded well at first, the overall health and function of the liver cells were negatively affected over time.
Who this helps: This helps patients with liver injuries by providing insights that could improve treatment strategies for liver regeneration.
Hepatic stellate cells' involvement in progenitor-mediated liver regeneration.
2010
Laboratory investigation; a journal of technical methods and pathology
Pintilie DG, Shupe TD, Oh SH, Salganik SV, Darwiche H +1 more
Plain English This study investigated how certain liver cells (hepatic stellate cells) affect the liver's ability to regenerate after damage. Researchers found that feeding rats a diet with L-cysteine, which prevents stellate cell activation, led to an 11-fold decrease in activated stellate cells and a more than fourfold reduction in the liver's oval cell response, indicating that active stellate cells are crucial for proper liver regeneration. These findings highlight the importance of targeting stellate cell activation in improving liver recovery after injury.
Who this helps: This research benefits patients with liver diseases by informing potential treatments for liver regeneration.
A detailed characterization of the adult mouse model of glycogen storage disease Ia.
2009
Laboratory investigation; a journal of technical methods and pathology
Salganik SV, Weinstein DA, Shupe TD, Salganik M, Pintilie DG +1 more
Plain English This study focused on a type of genetic disorder called glycogen storage disease type Ia (GSDIa), which affects liver function and causes severe low blood sugar. Researchers created a special mouse model to better understand the disease and found that, once these mice survived their weak early months, their health significantly improved, with their size and energy levels becoming similar to healthy mice. However, the underlying liver problems did not get better with age. This research matters because these adult mice can be used to test new treatments that were not previously possible in the fragile younger mice.
Who this helps: This helps researchers and doctors looking for effective therapies for patients with GSDIa.
Isolation and characterization of hepatic stem cells, or "oval cells," from rat livers.
2009
Methods in molecular biology (Clifton, N.J.)
Shupe TD, Piscaglia AC, Oh SH, Gasbarrini A, Petersen BE
Plain English This study focused on finding and studying liver stem cells, known as "oval cells," in rat livers. The researchers developed effective methods to isolate these cells and found that using a surface marker called Thy-1 along with magnetic sorting made it easier to gather these cells for further testing. Their work is important because it opens up new possibilities for using liver stem cells in therapies for liver diseases.
Who this helps: This helps researchers and doctors working on liver disease treatments.
Establishment of cancer cell lines from rat hepatocholangiocarcinoma and assessment of the role of granulocyte-colony stimulating factor and hepatocyte growth factor in their growth, motility and survival.
2009
Journal of hepatology
Piscaglia AC, Shupe TD, Pani G, Tesori V, Gasbarrini A +1 more
Plain English This study focused on creating cancer cell lines from liver tumors in rats to understand how specific growth factors, G-CSF and HGF, affect the growth and movement of these cells. Researchers successfully developed six cell lines from tumors and found that HGF helped the cancer cells survive, while G-CSF promoted their growth and movement. These findings are significant because they could lead to new treatments targeting these factors in liver cancer.
Who this helps: This benefits researchers and doctors looking for more effective therapies for liver cancer patients.
Granulocyte-colony stimulating factor promotes liver repair and induces oval cell migration and proliferation in rats.
2007
Gastroenterology
Piscaglia AC, Shupe TD, Oh SH, Gasbarrini A, Petersen BE
Plain English This study looked at how a protein called granulocyte-colony stimulating factor (G-CSF) helps the liver repair itself, particularly by affecting special cells known as oval cells, which are like stem cells for the liver. The researchers found that giving G-CSF to rats increased the activity of oval cells and boosted the contribution of bone marrow cells to liver recovery. Specifically, G-CSF enhanced the oval cell response significantly, indicating that this treatment improves the liver's ability to heal.
Who this helps: This helps patients with liver damage or disease by potentially improving treatment options for recovery.
Stem cells, cancer, liver, and liver cancer stem cells: finding a way out of the labyrinth..
2007
Current cancer drug targets
Piscaglia AC, Shupe TD, Petersen BE, Gasbarrini A
Plain English This study examined cancer stem cells (CSCs) in liver cancer to understand how they contribute to tumor growth and treatment resistance. Researchers found that CSCs not only help form most of the tumor but are also responsible for tumor regrowth after treatments fail. Understanding these cells can lead to more effective cancer therapies targeting them specifically, which is crucial because they play a significant role in the spread and persistence of cancer.
Who this helps: This helps patients with liver cancer and other types of cancer by potentially improving treatment outcomes.
A potential role of somatostatin and its receptor SSTR4 in the migration of hepatic oval cells.
2006
Laboratory investigation; a journal of technical methods and pathology
Jung Y, Oh SH, Zheng D, Shupe TD, Witek RP +1 more
Plain English This study focused on a substance called somatostatin (SST) and its potential role in helping liver cells, known as hepatic oval cells (HOCs), move to where they're needed. The researchers found that SST promotes the movement of HOCs by working through a specific receptor called SSTR4, where blocking this receptor significantly reduced cell migration. This matters because understanding how SST influences liver cell movement could help in developing treatments for liver diseases and improving liver regeneration.
Who this helps: This helps patients with liver diseases and doctors treating them.