Meet Researcher: Joel Pachter, UConn Health

Dr. Joel Pachter, professor of immunology, has always been fascinated by the central nervous system. His current research focuses on uncovering how this system plays a role in neuroinflammatory diseases like multiple sclerosis.

Joel S. Pachter, Department of Immunology, in his lab at UConn Health. (Kristin Wallace / UConn Photo)

When Dr. Joel Pachter was eight years old, his father gave him his first chemistry set. Since those early days of kitchen table experiments Dr. Pachter has established a productive research career studying the central nervous system as a tenured Professor in the Department of Immunology at UConn Health.

“As a kid I just used to play with chemicals and chemistry sets – now I get to do that for a living and I enjoy what I do, I am never bored,” Dr. Pachter says. “Every day is exciting, every day I learn something and so I continually think it’s an honor and pleasure to do what I do. For me it’s not a job, it never has been, it’s something I’ve always wanted to do.”

As an undergraduate, Dr. Pachter was fascinated by the central nervous system (CNS), which includes the brain and spinal cord. Specifically, Dr. Pachter was interested in how the CNS influences mental illness.

After graduation, Dr. Pachter completed a fellowship in psychopharmacology at the Mario Negri Institute for Pharmacological Research in Milan studying how drugs affect behavior and how the brain controls aspects of behavior.

Until relatively recently, people with mental illness were often institutionalized for life, in some cases under horrible conditions. With the advent of new pharmaceuticals, most people with mental illness can live independent lives.

“I was fascinated by how drugs could correct those behaviors and from there I became more and more fascinated by how the nervous system worked in general and so I just continued to pursue that,” Dr. Pachter says.

Taking Research Chances

After completing his fellowship at Mario Negri, Dr. Pachter obtained his Ph.D. in pharmacology at NYU, School of Medicine. He then completed a post-doctoral fellowship in the Department of Biological Chemistry at the Johns Hopkins School of Medicine. In 1987, he took a faculty position at UConn Health.

Dr. Pachter’s research has evolved since his arrival on the Farmington campus, now focusing on how the CNS plays a role in inflammatory diseases like multiple sclerosis (MS) and Alzheimer’s disease. Dr. Pachter has found that many of the same mediators that influence behavior and mental illness, also play a role in controlling inflammatory diseases.

Dr. Pachter explains that the CNS and immune system have an important relationship.

“We’re starting to understand that the brain and the immune system contact each other regularly and interact and that certain diseases are the result of imperfect or disturbed communications between the immune system and the nervous system,” Dr. Pachter says. “I’m again very fortunate to be at the dawn of that kind of research. We’re just beginning to open some doors and understand the interactions between the systems.”

One application for this work is in using stem cells to treat MS. Dr. Pachter is working with ImStem Biotechnology, a UConn TIP company, on clinical trials.

The thought behind this approach is that stem cells are a naturally occurring part of the body. Stem cells can, in theory, produce or repair any cell type. Stem cells also play an important role in suppressing the inflammatory response in MS.

Dr. Pachter’s work is in coaxing the stem cells to engage in their natural functions in a way that will help repair the nervous system.

“Now we find that it’s not just their replacement capability, but the fact that these are little, basically, drug stores of lots of anti-inflammatory factors that can release these anti-inflammatory factors and quiet down a situation that’s inflamed and then allow the brain and the spinal cord to begin to repair itself,” Dr. Pachter says.

Pre-clinical studies showed the stem cells could enter the brain and spinal cord to execute therapeutic effects for MS in mouse models.

Dr. Pachter is also currently working on a study of the meninges, the triple-layered membrane that covers the brain and spinal cord.

For years, scientists believed the meninges were just protective casings for the CNS. In recent years, it has become clear that the meninges are the site where inflammation originates and that even minor changes to the meninges can impact the brain or spinal cord.

Dr. Pachter is using cutting-edge imaging technologies to better understand how the meninges work under normal and pathological conditions.

Better understanding the meninges’ function may open the door to new therapeutics. Since the meninges are on the surface of the brain and spinal cord, they can be more easily accessed for surgery or pharmaceutical interventions.

Another area of Dr. Pachter’s current research is looking at extracellular vesicles. These tiny particles carry proteins, nucleic acids, lipids, and other components between cells. They are released by almost every cell type in the human body. Dr. Pachter is looking at the extracellular vesicles released by the cells that form the lining of blood vessels in the brain.

I like to think that I’m always at the boundary of what’s pioneering out there. — Dr. Joel Pachter

Dr. Pachter hypothesizes that these vesicles facilitate communication with white blood cells, which combat infection in the body. These cells are also responsible for neuroinflammatory disease. Dr. Pachter is investigating how these vesicles direct the blood cells to the brain and spinal cord at the beginning of neuroinflammatory disease.

“The more we know about that communication, the more likely we are to be able to develop means to antagonize that and prevent that from happening,” Dr. Pachter says.

Throughout his career as a researcher, Dr. Pachter’s work has focused on taking chances and working on the cutting-edge of science.

“I like to think that I’m always at the boundary of what’s pioneering out there,” Dr. Pachter says. “I like to take chances. Chances make the work very exciting.”

“Biology Isn’t Simple”

One lesson Dr. Pachter tries to impart to his students is that “biology isn’t simple.” Understanding how the body works under normal conditions allows scientists to then understand how they work under pathological conditions and develop treatments.

“I think it’s important to understand how critical it is to look at where disease originates from instead of looking at disease at the end of the line,” Dr. Pachter says. “If we’re starting to appreciate that a lot of inflammatory diseases actually begin in the meninges, if we can target therapies to those sites, we’re more apt to be able to put the disease process on hold than if you were to have to work so far downstream where the disease has already progressed.”

Dr. Pachter says that after decades in the field, he is still constantly surprised and excited by this work, which looks different every day.

“A career in science is something that should be looked at as a true honor that you’re able to do things that no one else has done before and you can leave your imprint on society just by making even the slightest discoveries,” Dr. Pachter says. “You never know who’s going to pick up on those discoveries and advance them in such a way that they have tremendous impact.”

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