Our Work
Understanding Cancer Stem Cells
Cancer is a disease where the cells in our body grow uncontrollably and can cause a lot of harm. Scientists have found that there are special cells in some types of cancer called cancer stem cells (CSCs) that are really good at growing and dividing, even when we try to use medicine to stop them.
One type of cancer with these CSCs is glioblastoma (GBM), a really dangerous brain tumor. There are two types of cells in a GBM tumor: the CSCs and the cancer cells that come from the CSCs. These two types of cells work together to keep the tumor growing.
Scientists have found that how these cells divide and grow is important to understand how the tumor grows and why it is so hard to stop. They are studying this using models and samples from patients to figure out how these cells work and how we might be able to stop them from growing.
By understanding more about these cells and how they work, Our lab hopes to find new treatments to stop cancer from returning after it has been treated. It's really important to work because GBM is a very dangerous disease, and we need to find new ways to treat it.
Tackling Cancer Cell Plasticity
Cancer cell plasticity refers to the ability of cancer cells to change their characteristics in response to different signals from their environment. This means that cancer cells can switch back and forth between different states or types, such as stem-like cells or differentiated cells.
This plasticity is thought to play a role in the ability of cancer cells to resist therapy and to spread to other parts of the body, which is why it is an important area of study for cancer researchers. We and others have shown that cancer therapy can promote plasticity and help cancer cells to survive therapies, The goal of our laboratory is to understand how cancer cell plasticity works, and we hope to develop new therapies that can prevent cancer cells from switching to more aggressive states and spreading throughout the body.
Blocking Epigenetic Plasticity in Cancer
Epigenetic plasticity in cancer refers to the ability of cancer cells to alter their gene expression patterns without changing the underlying DNA sequence. Epigenetic changes are modifications to the DNA molecule or to the proteins that package the DNA, and they can affect how genes are turned on or off.
In cancer, epigenetic changes can alter the expression of genes that control cell growth and division, making cancer cells more aggressive and resistant to therapy. For example, cancer cells may turn off genes that promote cell death or turn on genes that promote cell survival.
Our lab has shown that anti-cancer therapies can promote epigenetic plasticity and allows cancer cells to adapt to changes in their environment and to resist therapy. By studying epigenetic changes in cancer during therapy hope to develop new treatments that can reverse or block these changes and prevent cancer cells from becoming more aggressive or resistant to therapy.
Bench to Bedside
We are ecstatic to open our first clinical trial, evaluating an FDA-approved drug that can be repurposed to target plasticity-driven chemoresistance in brain tumors. Our lab has found that during treatment, some of the other cells in the tumor can change into these therapy resistance cancer stem cells, making the tumor even harder to treat. But we have also found a drug called Mycophenolate mofetil (MMF) that can help make the tumor cells more sensitive to treatment. This drug has already been approved by the FDA for other uses, but we want to see if it can be used to help treat GBM.
In order to test this, we're going to do a clinical trial with patients who have newly diagnosed GBM. We will give them the usual chemotherapy and radiation treatments, but we will also give them MMF to see if it can help improve the treatments. We will check to make sure that MMF is safe and does not cause any bad side effects, and we will also look at how long the patients live without the tumor getting bigger (progression-free survival) and how long they live overall (overall survival).
By using MMF to help treat GBM, we hope to find a new way to make the treatments work better and help patients live longer. We also hope this new treatment approach can be used for other types of cancer.
A Pandemic Project: YouTube Channel for Lab Skills
One of our lab's critical pandemic missions was to survive the current pandemic and do everything within our power to prepare for the next one. With this in mind, we have made all our lab protocols and training materials available to the public by creating an open-access YouTube channel. To date, we have released 18 virtual training videos for some of the fundamental skills required to become a wet lab researcher, including how to formulate a testable hypothesis and set up experiments to test your hypothesis, ethical interpretation of data, and elementary methods to write a grant proposal.
This effort was led by Shivani Baisiwala, MD, a lab alumnus currently at UCLA Neurosurgery as a PGY3 Resident Physician. For the past two years, our channel has been viewed in 60 countries with over 22,000 teaching hours and received over 2 million impressions.
We want to introduce these resources to all budding scientists worldwide and empower a new generation of researchers so that we can be ready for the next pandemic.