Fighting cancer with the help of viruses

Majumder, Assistant Professor of Oncology at the UW Institute for Molecular Virology and UW Carbone Cancer Center researcher, studies the mechanisms of how oncolytic, or cancer-targeting, viruses alter cell development as well as how parvovirus vectors can be engineered as a method of precision cancer treatment.

Majumder’s goal is to uncover which cell proteins these cancer-targeting viruses are attracted to, how they take control of those proteins, and the effects of that process.

“No one knows,” Majumder said. “We think that oncolytic viruses go to broken DNA regions because when there’s a DNA break, there are about 200 different proteins that are recruited to repair it. We think the viruses hijack these proteins and use them for their own benefit.”

These oncolytic viruses latch onto and utilize their host’s proteins so that they do not have to produce or carry their own. The viruses’ takeover of cancer cells causes DNA damage just like radiation and chemotherapy, leading to cancer cell death.

Understanding how viruses affect host cells can help researchers flip the script and modify those mechanisms to benefit patients. Majumder’s lab studies the therapeutic use of parvoviruses, which are small DNA viruses that rely extensively on mechanisms in the host cell’s nucleus, in particular the DNA Damage Response machinery that ensures healthy cell development and usually protects against cancer.

In parvovirus-based gene therapy, the vectors express corrective genes that can be given to patients to treat a genetic disease or deliver a suicide gene to cancer cells. Some of these viruses can also be used to make immunotherapy-resistant “cold” tumors become receptive, or “hot” to effective treatment.

“These oncolytic parvoviruses can turn cold tumors into hot tumors by inducing DNA damage, which generates signals that activate local immune cells,” Majumder said.

To create gene therapy vectors, Majumder’s lab takes a parvovirus and strips out all of the proteins that it normally expresses. In place of these proteins, Majumder manipulates the parvovirus to carry normal human genes into the cells in which there is a genetic mutation, thereby treating the disease that lies within.

Majumder collaborates on this work with Dr. Kavi Mehta, assistant professor in the Department of Comparative Biosciences, and Dr. Joshua Coon, professor in in the Departments of Chemistry and Biomolecular Chemistry.

“It is a multi-partner collaboration,” Majumder said. “Using the mass spectrometers that they have, we are looking at how these parvoviruses cause global changes to different small molecules within a cell.”

Majumder’s lab recently hit its three-year mark, and what the lab looks like now in comparison to October 2020 is completely different due to the COVID-19 pandemic. He is grateful that the UW community is very engaged in scientific research. Otherwise, there would have been a slow start to his laboratory.

“Everybody is very supportive, so collaborative.” Majumder said. “It’s helped me establish my program and build momentum. There is a lot of expertise to draw on and get input from.”

Majumder hopes to be a mentor for his team of students, and to all new faces in the lab that are trying to pave their future path in research.

“Even though this was an empty space, we got experiments going right away because colleagues in the IMV gave me bench space in their lab. That made all the difference, and it is something that I try to do with new investigators that come in. Pay it forward,” Majumder said.