Highlighted Faculty Publication

Defensive Maneuver

Sahin, I., Zhang, S., Navaraj, A., Zhou, L., Dizon, D., Safran, H., & El-Deiry, W. S. (2020). AMG-232 sensitizes high MDM2-expressing tumor cells to T-cell-mediated killing. Cell Death Discovery, 6(1), 57. doi:10.1038/s41420-020-0292-1

Immunotherapy fails in a significant proportion of cancer patients. But a new study in Cell Death Discovery suggests that blocking the tumor-promoting protein MDM2 could bolster the treatment’s effectiveness.

“Immunotherapy has been one of the biggest breakthroughs in biomedical science and medicine of the last two decades,” says Wafik S. El-Deiry, MD, PhD, a professor of pathology and laboratory medicine and associate dean for oncologic sciences. “But it has limitations.”

Some people’s tumors respond to immunotherapy initially and then relapse. Other patients experience pseudoprogression, where tumors appear to grow before eventually shrinking. And a third group—between 5 percent and 29 percent of patients—experience hyperprogression: immunotherapy actually worsens their tumor growth.

El-Deiry hopes that blocking MDM2, either through gene silencing or the MDM2-inhibiting drug AMG-232, could help people with hyperprogression.

Various studies have found that when cells contain too many copies of the MDM2 gene, or when the MDM2 protein is overexpressed because the gene isn’t being regulated properly, tumor cells tend to grow more quickly and are more resistant to immunotherapy. MDM2 is also associated with higher levels of the tumor-promoting inflammatory protein interleukin-6 (IL-6).

In their study, El-Deiry and his colleagues treated cell lines of MDM2-overexpressing ovarian cancer cells with AMG-232. Their data show the drug allowed immune cells to kill the tumor cells much more efficiently, and reduced levels of IL-6. This suggests that MDM2 inhibitors combined with immunotherapy could enhance its effectiveness, and El-Deiry hopes this will lead to a clinical trial.

The study was published shortly after the launch of the Cancer Center at Brown, which brings together 150 investigators from across the University and affiliated hospitals who are studying basic biology and disease epidemiology, understanding risk factors, and developing therapies.

The center focuses on cancers with higher rates in Rhode Island, as well as issues of access and affordability. El-Deiry, the center’s inaugural director, wants the center to achieve a National Cancer Institute-Cancer Center Support Grant.

“We are working methodically, in a focused way, toward that,” he says, “collaborating for the benefit of patients.”

Assistant Professor Jessica Plavicki receives the Outstanding New Environmental Scientist (ONES) Award from the National Institute of Environmental Health Sciences

Assistant Professor Jessica Plavicki is the recipient of an Outstanding New Environmental Scientist Award (ONES) from the National Institute of Environmental Health Sciences. This highly selective award is an R01 that recognizes promising early stage investigators who have the potential to become leaders in the field of environmental health sciences. In addition to an R01 budget, recipients receive an additional $250k in support of career development.  More information about the ONES can be found here: https://www.niehs.nih.gov/research/supported/training/ones/index.cfm

Layra Cintón-Rivera, a Pathobiology graduate in the Plavicki Lab, is awarded a NSF graduate student research fellowship

Layra Cintón-Rivera, a Pathobiology graduate in the Plavicki Lab, is the recipient of a NSF graduate student research fellowship. This prestigious fellowship recognizes and supports outstanding graduate students in NSF-supported STEM disciplines who are pursuing research-based master's and doctoral degrees at accredited US institutions. More information about the NSF fellowship program can be found here: https://www.nsfgrfp.org/

Jessica Plavicki is named the Manning Assistant Professor in Pathology and Laboratory Medicine

Jessica Plavicki has been named the Manning Assistant Professor in Pathology and Laboratory Medicine. The Manning Assistant Professorships, which honor the first president of Brown University, James Manning, Brown's were established by Martha Sharp Joukowsky, Class of 1958, LHD 1985, and Artemis A. W. Joukowsky, Class of 1955, LLD 1985, the parents of Michael W. Joukowsky, Class of 1987.

Assistant Professor Daniel Spade, PhD receives COBRE pilot award

Assistant Professor Daniel Spade, PhD, receives pilot award from the Center for Biomedical Research Excellence (COBRE) for Reproductive Health at Women and Infants Hospital, for the project, "Identification of sperm RNAs that predict ICSI outcomes." Additional information about the COBRE for Reproductive Health can be found here.


Sir Nicholas Wald elected to National Academy of Medicine

It is a great honor as we congratulate Sir Nicholas Wald, MBBS, DSc, Consultant of our Division of Medical Screening and Special Testing of Women & Infants Hospital and Adjunct Professor of Pathology & Laboratory Medicine of Alpert Medical School of Brown University, elected to the prestigious National Academy of Medicine (NAM).  You may learn more about the honor and the citation of Sir Wald through abstract of NAM news release below.  The full news release is available at https://nam.edu/national-academy-of-medicine-elects-100-new-members/