McLean Researchers Win Prestigious Alfred Pope Award for Young Investigators

McLean researchers Joanna A. Korecka, PhD, assistant neuroscientist at the Neuroregeneration Research Institute (NRI), and Galen Missig, PhD, a research fellow in the Behavioral Genetics Laboratory, are the 2019 winners of the Alfred Pope Award for Young Investigators. It is one of McLean’s highest research honors.

This annual award honors the innovative work of young researchers at McLean. It is named for one of the hospital’s most distinguished and respected researchers, the late Alfred Pope, MD. The award specifically recognizes the publication of an exceptional peer-reviewed, first-authored article on basic or clinical research performed at McLean. It also includes a $750 cash prize.

“McLean is honored to give this award to two extremely talented and hardworking investigators,” said McLean Chief Academic Officer Shelly F. Greenfield, MD, MPH. “Their research has already made important contributions toward helping us better understand neuropsychiatric mechanisms underlying psychiatric disorders.”

Missig’s research is aimed at finding new ways in which the nervous system and the immune system are closely connected. He discussed his award-winning paper, “Sex-Dependent Neurobiological Features of Prenatal Immune Activation via TLR7,” at a special Grand Rounds lecture on June 6.

Missig noted that recent studies have shown a strong link between inflammatory conditions during pregnancy and psychiatric illnesses in offspring. Such research has largely focused on the influence of maternal inflammation resulting from particular pathways in viral or bacterial infections. Yet, said Missig, the roles of other autoimmune-related pathways have been relatively unexplored.

Missig developed a new mouse model of maternal inflammation. To evaluate how inflammation during pregnancy may affect offspring he used an activator of toll-like receptor 7 (TLR7). Toll-like receptors are proteins involved in human immunity. TLR7 is believed to play a role in the development of autoimmune disorders.

“The outcomes of prenatal TLR7 activation were quite different from prior models,” said Missig. “They included increased but fragmented social behaviors and hyperactivity. We also found that there were many changes in gene expression in the brain that were completely different between males and females.”

Missig believes that the results of this new model should help guide further research on the relationship between the nervous system and the immune system.

“This research shows how outcomes of prenatal immune activation can vary according to the type of immune pathways activated,” explained Missig. “This may provide a clue as to how prenatal immune activation can be associated with a wide array of psychiatric conditions. It also suggests that untangling the specific immune pathways involved may be critical for understanding how these conditions develop.”

A Phyllis and Jerome Lyle Rappaport Mental Health Research Scholars Award and the Robert and Donna Landreth Family Fund made this initial work possible. Missig also recently received a fellowship and a NARSAD Young Investigator Award to support the next steps of his work.

Korecka, meanwhile, is studying intracellular calcium homeostasis. This involves keeping a healthy balance of calcium within a cell.

Keeping such a balance has been shown to be critical for a cell’s health. Failure to maintain this balance has been linked to neurodegeneration in Parkinson’s disease (PD).

For her paper, Korecka examined a specific gene mutation associated with PD. She used stem cell-derived neurons from patients with PD to study this mutation.

“We found that intracellular calcium homeostasis was altered in patients with the LRRK2 G2019S mutation,” said Korecka. “It was altered in the cellular compartment known as the endoplasmic reticulum (ER). The ER is one of the largest cellular compartments. It handles calcium storage, protein folding, and initiating protein transport. All of these tasks are important for neuronal function and health.”

Korecka said this impairment could contribute to the cellular vulnerability seen in PD.

“We hope this research helps unravel a specific mechanism of the neurodegenerative process in PD,” said Korecka. “If further studies confirm that ER calcium homeostasis is part of the disease’s onset, controlling this neuronal function may be an attractive therapeutic target.”

Korecka recently received the 2019-2020 Eleanor and Miles Shore Harvard Medical School Fellowship. This will enable her to further study ER calcium homeostasis in PD.

Both Missig and Korecka expressed their deep appreciation for receiving the Pope Award.

“I am honored to receive the Alfred Pope Award,” said Missig. “It is meaningful and valuable to receive such an award at this early stage of my career. I also recognize its connection with McLean’s rich legacy of scientific discovery.”

“It is an honor to be the co-recipient of this award,” added Korecka. “It is also a wonderful recognition of the effort of my team at the NRI and our collaborators. It further inspires me to continue my mission to help find a novel therapeutic target for Parkinson’s disease.”

“The work from Drs. Missig and Korecka are fine examples of the outstanding and unique basic and translational research taking place every day at McLean,” said Kerry J. Ressler, MD. PhD, McLean’s chief scientific officer. “Their research is helping us identify novel approaches to treatment and intervention for devastating mental disorders.”