The Mansfeld Lab

 

Cell Cycle

 

To divide, or not to divide? That is the question.

 

​Our bodies are made of trillions of cells. But in the beginning, there was only one. It divided to give rise to two cells, which later became four and so on. To divide, each cell goes through a strict order of events called the cell cycle. These events include duplicating everything within the cell, so that there will be enough to eventually make two cells, and then checking that everything has been duplicated correctly before division.

 

But division is not the only fate for cells – they can also decide to stop dividing and become dormant. In fact, an adult human body consists mostly of dormant cells. There is still a lot for us to understand about how cells make decisions throughout the cell cycle, such as this decision between dividing or becoming dormant.

 

Our laboratory aims to discover more about how cells make these decisions, and what happens when this decision-making goes wrong; for example, uncontrolled cell division which can cause cancer.

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AI-podcast: Quantitative Cell Cycle Analysis Using an Endogenous All-in-One Reporter

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Protein Modifications

 

Most jobs that happen in our cells – essential processes that keep us alive – are carried out by large molecules called proteins.  For example, proteins are needed for various jobs during the cell cycle; these are called cell cycle proteins.

 

Certain molecules can be temporarily added to a given protein, thus ‘modifying’ the protein. This can change its activity, like what type of job it carries out, or when.

 

Our lab investigates how specific protein modifications affect the activity of cell cycle proteins, especially modifications that are common in cancer.

 

AI-podcast: E2 Thioester-Driven Substrate Identification: A Versatile Approach

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Reactive Oxygen Species (ROS)

 

One type of molecule that can modify proteins is reactive oxygen species (ROS). As the name suggests, ROS are extremely reactive and can damage lots of delicate structures within cells. An example of ROS is hydrogen peroxide, the chemical we use to bleach hair and clean bathrooms. ROS are produced by many processes that happen continuously in cells – including the processes that keep us alive!

 

So, if cells can’t avoid producing ROS, then how do they deal with this problem? They produce antioxidants (which can also be found in health foods, like blueberries and dark chocolate) to soak up the harmful ROS molecules.

But there’s a twist in the story: in small amounts, ROS may be needed by the cell, to modify proteins and therefore change their activities. Protein modification by ROS is not widely studied, so our lab is investigating the importance of these modifications, especially for processes that are linked to cancer, such as the cell cycle. We have already found some proteins that need to be modified by ROS to complete the cell cycle correctly!

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AI-podcast: Mitochondrial ROS Regulate Cell Cycle via CDK2 Oxidation

 

 

 

 

 

AI-podcast: p21's Redox Switch: Cell Cycle and Senescence Control

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​​Our translational work

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Our research into cell cycle regulation, protein modifications, and reactive oxygen species (ROS) uncovers fundamental principles of how cells decide when to divide or rest. When this decision-making process fails, it can lead to diseases such as cancer.

By understanding these underlying mechanisms, we aim to identify new vulnerabilities in cancer cells — entry points that can be exploited for therapeutic intervention. To translate our discoveries into potential treatments, we collaborate closely with structural and computational biologists to design targeted inhibitors, and with clinicians to explore their relevance in patient-derived models. Through this multidisciplinary approach, we are working to turn insights from basic biology into new strategies for targeted and selective cancer therapy.

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AI-podcast: Targeting RING E3 Ubiquitin Ligases with De Novo Inhibitors

 

 

 

 

 

In everything we do, we always consider how our molecules can be best delivered to the right cells. Sometimes, this requires developing entirely new technologies—for example, methods to physically squeeze cells. Curious how that works? Listen to our AI podcast below and/or read the accompanying publication:

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AI-podcast: Progressive Cell Membrane Mechanoporation for Cargo Delivery

 

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**AI-podcasts are created by NotebookLM using own publications as sole sources** 

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