U2-Physicians 3F Hall Hub Back-hero

Making New Memories with the MCW School of Pharmacy

Making new memories with the MCW School of Pharmacy with Nashaat Gerges, PhD, BPharm

While Nashaat Gerges, PhD, BPharm, has been a faculty member at the Medical College of Wisconsin since 2006, he only recently joined the MCW School of Pharmacy, six months before the orientation of its inaugural class in 2017. While welcoming the challenge of helping build and shape the new pharmacy school, he also has continued his previous research. “Ever since the first rotation in a neuroscience lab, I fell in love with neuroscience. I have been working on the same region of the brain since then – the hippocampus,” he says. The hippocampus is a part of the brain that plays an important role in learning and memory.

Dr. Gerges has presented his research at many national and international conferences, including at the Federation of European Neuroscience forum in Germany, the Calcium Signaling Gordon Research Conference in Italy, the Excitatory Synapses Gordon Research Conference in Switzerland, the Molecular & Cellular Neurobiology Gordon Research Conference in China, and the Mediterranean Neuroscience Conference in Egypt. He has received awards from the National Institute of Health (NIH), Alzheimer’s Association, American Thyroid Association, BrightFocus Foundation, and Advancing a Healthier Wisconsin (AHW) Endowment. Work from Dr. Gerges’ lab has been published in highly prestigious journals, e.g. Nature Neuroscience, the EMBO Journal and the Journal of Neuroscience. His work has been highlighted in various avenues nationally and internationally, including commentaries in Biology - F1000, the EMBO Journal and the Journal of Neuroscience.

One of Dr. Gerges’ major research areas is the investigation of a protein called neurogranin. Neurogranin is important because it enhances synaptic plasticity, which is thought to be the cellular mechanism of learning and memory. Because of this, neurogranin has the potential to improve memory deficits related to Alzheimer’s disease or aging.

Neurons are the basic functioning cell of the nervous system, including the brain. Neurons transmit messages to each other through tiny contacts called synapses. Synapses have plasticity, meaning that the strength of the communication across them can change over time. In normal functioning, communication across synapses that are used more often are more likely to grow stronger, or potentiate, while communication across synapses that are used less often will likely become weaker or depress. Long-term synaptic plasticity describes how these changes can last over long periods of time, such as minutes to years.

In a normal functioning brain, our neurons have the ability to both potentiate and depress. “In order for our synapse to be able to adapt, they have synaptic plasticity – this is normal. We learn a lot of things and learning includes synaptic potentiation, which is thought to be important for long-term memory. On the other hand, our brain will be overloaded if we don’t have the ability to delete the unnecessary information. In everyday life we need this continuous balance between synaptic potentiation and depression,” Dr. Gerges says.

An example of short-term synaptic plasticity is trying to remember where you have parked your car. If you’re trying to find where you parked your car after work, you may or may not remember. However, if someone asks where you parked your car last month, you almost certainly won’t remember. That’s because the information is no longer useful to you.

However, in disease states such as Alzheimer’s disease, it has been noticed that synapses shift to having less ability to undergo long-term potentiation and instead have more long-term depression. This can have multiple effects and might explain why Alzheimer’s patients begin to have impaired memory.

Dr. Gerges’ working hypothesis is that neurogranin may help shift this balance back and allow synapses to regain plasticity. Neurogranin is able to target more of a messenger protein called calmodulin in the synapse, which as a result can make it easier for the synapse to potentiate.

Using a multidisciplinary approach combining electrophysiology, biochemistry, confocal imaging and electron microscopy analysis, Dr. Gerges’ lab showed that through its ability to target calmodulin, neurogranin enhances synaptic plasticity and lowers the threshold for potentiation. Even in the presence of a molecule called amyloid beta peptide, which is known to cause synaptic depression and is suspected to be one of the causes of the symptoms experienced by patients with Alzheimer’s disease, neurogranin was still able to potentiate synapses.

Since synaptic plasticity is the cellular model for learning and memory, Dr. Gerges wanted to test whether increasing neurogranin in animal models would enhance learning and memory. To this end, Dr. Gerges’ lab created transgenic, or genetically altered, mice that have more neurogranin than usual. His studies showed that the increased levels of neurogranin enhanced learning and memory.

Dr. Gerges’ current work is focusing on understanding how neurogranin is regulated within the cell. Gaining this insight will help toward finding different drugs or other pathways that can increase neurogranin in the brain, which may lead to enhancing learning and memory.

Dr. Gerges is planning on creating future projects that will allow the MCW School of Pharmacy Doctor of Pharmacy (PharmD) students to get involved in his lab. Students at the MCW School of Pharmacy have different avenues available to them in which they can gain research experience, such as through a longitudinal course alongside medical students called Scholarly Pathways. Students are able to choose a Scholarly Pathway focused on research and can elect to complete and present a scholarly project. “Developing knowledge and insight into the scientific research setting really enhances the students’ future,” says Dr. Gerges. “It can increase their marketability and can open up their eyes to new career options.”

Beyond research, Dr. Gerges also works on curriculum oversight for the MCW School of Pharmacy. He helped to develop the curriculum that is currently being used and continues to work on improving curriculum delivery. He teaches in multiple courses, including Human Anatomy and Physiology, Integrated Sequence: Endocrine, and Integrated Sequence: Neurology and Behavioral Health.

“MCW is a great place to work, where collegiality is exceptional. I have the unique privilege that I have had primary appointments in two major schools within MCW, the School of Medicine and the School of Pharmacy, in addition to serving the Graduate School,” Dr Gerges says. “It’s an honor to be able to help train the next generation of physicians, pharmacists and scientists.”