Shannon Martin Receives NRSA Award

Shannon Martin, 4th Pathobiology Graduate Student in the Plavicki Lab, received a Ruth L. Kirschstein Predoctoral Individual National Research Service Award (F31) from NHBLI. The title of her fellowship project is "Determining the role of macrophages in the developing cardiac conduction system".

Forensic Pathologist Dr. Priya Banerjee: Learning From the Dead to Help the Living

Dr. Priya Banerjee is at home with mementos of the dead. Bones and skulls from animals and artificial human remains decorate her house the way a gardener would fill their home with flowers. There are vegetables bursting from a giant skull dish, and the skeletal paws of a mother bear killed in Cranston years ago are mounted on a plaque and raised as if in supplication. Candy bones decorate her homemade French macarons, and a collection of skulls and skeletons adorn nooks and crannies throughout her home.

Please view the article on the Boston Globe below:

Forensic pathologist Dr. Priya Banerjee: Learning from the dead to help the living

September Faculty Accomplishments

Grants

Jeffrey Bailey, Associate Professor, received $483,122 for “Molecular surveillance of malaria in Tanzania.” The grant is a subaward through the National Institute for Medical Research from the Bill and Melinda Gates Foundation. 

Publications

Thomas Bartnikas, Associate Professor, publishes "Cutting not the key to TMPRSS6 activity?" in Blood. Full article can be found here

Alok Das Mohapatra, Postdoctoral Research Associate, publishes first-author paper in Cancer Immunology Research, titled "Cross-dressing of CD8α+ dendritic cells with antigens from live mouse tumor cells is a major mechanism of cross-priming." Full article can be found here

New Research Awards for Faculty

The July 2020 issue of Kudos, the newsletter for the Division of Biology and Medicine at Brown, recognized Department faculty who received research awards.

Jeffrey A. Bailey, Pathology and Laboratory Medicine, received $40,250  for “Age-associated development of antibody-mediated cytotoxic immunity to SARS-CoV-2, the virus that causes COVID-19 Disease.” The grant is a subaward through the University of Massachusetts Medical School from the Massachusetts Consortium on Pathogen Readiness. 

Kim Boekelheide, Pathology and Laboratory Medicine, received $500,000 for “Implementation of a Human Liver Two-Compartment Metabolizing System” from Unilever.

Alexander Brodsky, Pathology, RIH, received $573,040 for “Collagen Variants Sensitize Stomach Tumors to Therapeutics” from the Department of Defense. 

Jonathan D. Kurtis, Pathology and Laboratory Medicine, received $134,493 for “One Health Vaccine Development for Bovine and Human Schistosomiasis, a Research Supplement to Promote Diversity in Health-Related Research” for Amanda Ruiz from National Institute of Child Health and Human Development (NICHD).

Shaolei Lu, Pathology, TMH, received $79,650 for “COVID-19 Antibody Surveillance Research Support” from the Rhode Island Department of Health.

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.”

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