Highlights and News

Spring 2016 Edition of Vitals

The University of Virginia has released the Spring 2016 Edition of their e-magazine Vitals. You will see a few familiar faces! Congratulations!

Congratulations to MSTPs who are heading back to Clerkships!

Join us in congratulating the following Grad students on successfully defending their dissertations: Jim Cronk, Eve Privman Champaloux, Sachin Gadani, and Sowmya Narayanan! We wish them the best as they head back to Medical School!

MSTP Jim Cronk wins 2016 Michael Peach Award

Please join us in congratulating Jim Cronk (Kipnis lab) who won the prestigious Michael J. Peach Award.  Jim, Janelle Weaver (Outstanding Student, Pharmacology) and Sam M. Rosenfeld (Outstanding Student, Pathology/MCBD) all gave terrific oral presentations that were extremely well received at the 24th Annual GBS Symposium, Monday March 21st.

We couldn’t be prouder!

Congratulations! MSTP Med 4s Match Day, March 18th

Please join us in congratulating three outstanding MSTPs who matched at Chicago, UCSD, and Johns Hopkins in Internal Medicine, Ophthalmology, and Neurology. We wish them the very best! To view our full Match List, click here! To view a great video of the Match Day experience, click here!

 

MSTP Annual Student/Alumni Presentations: April 15

The MSTP is honored to host Oliver McDonald, MD, PhD as this year’s Alumni speaker. Dr. McDonald is an Assistant Professor of Pathology at Vanderbilt and a graduate of Dr. Gary Owens’ lab. Our student speaker will be Sowmya Narayanan, Grad 4, Hahn Lab. Sowmya will defend this summer and return to medical school. Congratulations!

U.Va. Finds Trigger for Protective Immune Response to Spinal Cord Injuries

Gadani2015Hot on the heels of discovering a protective form of immune response to spinal cord injury, researchers at the University of Virginia School of Medicine have pinpointed the biological trigger for that response – a vital step toward being able to harness the body’s defenses to improve treatment for spine injuries, brain trauma, Alzheimer’s disease and other neurodegenerative conditions.

The trigger for the immune response, the molecule interleukin-33, is concentrated in what is known as “white matter” in the healthy brain and spinal cord. Interleukin-33, the researchers have discovered, is released upon injury and activates cells called glia, beginning the body’s protective response and promoting recovery.

“It’s the first thing that tells the immune system that something’s been damaged,” said U.Va.’s Sachin Gadani, the lead author of a new paper outlining the discovery. “It’s how the immune system initially knows to respond.”

The researchers aren’t sure if interleukin-33 has other roles to play in addition to its role in injury response. “Interleukin-33 must be important to the central nervous system. It is expressed all the time – even in the healthy state – and we’ve only described its activity after injury,” said Jonathan Kipnis, a professor in the Department of Neuroscience and director of the Center for Brain Immunology and Glia. “From an evolutionary perspective it makes little sense. The system produces this constantly just in case of injury that may never come? I’d be surprised if there was no function beyond injury. IL-33 may represent a language through which [the central nervous system] is constantly talking with the immune system – or, in other words, a molecular mind-body connection.”

Kipnis noted that problems with interleukin-33 could contribute to poor outcomes after spine or brain injuries. “It’s possible that if there’s some problem with this molecule in patients, they will have poor alarm signaling, and they will have very poor outcomes,” he said.

The discovery also sheds light on previous findings connecting interleukin-33 to Alzheimer’s disease.

“There’s a huge link,” Gadani said. “Researchers have identified a strong connection between interleukin-33 and Alzheimer’s disease, and our work will pave the way for future studies on this topic.”

Eventually, the findings could lead to both improved treatments and new diagnostic tests for brain and spinal cord injury, Alzheimer’s and other conditions.

Kipnis saluted Gadani for his contributions to the work – contributions all the more impressive considering that Gadani is still a graduate student in U.Va.’s Medical Scientist Training Program.

“He came in with this idea, and from the initial idea to the final paper, he drove the research. And he’s only in his third year of graduate school,” Kipnis said. “Credit goes to our MST program that it is able to recruit such a high caliber of students.”

The findings have been published online by Neuron, a premier neuroscience journal for peer-reviewed research. The article’s authors are Gadani, James T. Walsh, Igor Smirnov, Jingjing Zheng and Kipnis.

Josh Barney
U.Va. Health System
jdb9a@virginia.edu
434-243-1988

Major Discovery on Spinal Injury Reveals Unknown Immune Response

Jamie Walsh, MSTP Student

Jamie Walsh, MSTP Student

In a discovery that could dramatically affect the treatment of brain and spinal cord injuries, researchers at the University of Virginia and elsewhere have identified a previously unknown, beneficial immune response that occurs after injury to the central nervous system. By harnessing this response, doctors may be able to develop new and better treatments for brain and spinal cord injuries, develop tools to predict how patients will respond to treatment, and better treat degenerative conditions such as Alzheimer’s disease, multiple sclerosis, glaucoma and Lou Gehrig’s disease.

The newly discovered immune response occurs independently of the process that typically goads the immune system into action. In that process, the body identifies and attacks substances known as antigens, such as bacteria and viruses.

“What we have shown is that the injured central nervous system talks to the immune system in a language that hasn’t been previously recognized in this context,” said Jonathan Kipnis, a professor in the Department of Neuroscience at U.Va.’s School of Medicine and director of the Center for Brain Immunology and Glia. “It sends ‘danger signals’ and activates the immune system very rapidly. These danger signals cause immune cells to produce a molecule called interleukin 4, which happens to be indispensable for immune-mediated neuroprotection after [central nervous system] trauma.”

Interleukin 4 helps protect the body’s neurons (nerve cells) and promote their regeneration, whereas uncontrolled inflammation can destroy them. As such, understanding how the body responds to damage to the central nervous system is critically important.

“Once [central nervous system] neurons die, they’re gone for life. They don’t come back. So I think the CNS has evolved along with the immune system to respond in this protective fashion,” explained U.Va.’s James T. Walsh, lead author of the paper outlining the discovery. “[The immune system in the CNS] has to be very metered with how it responds. It can’t attack everything like it does in a lot of other tissues, because it causes a lot of collateral damage. You really need the right kind of response in the CNS. It can be a double-edged sword. The immune system can cause damage to the CNS, but it can also be beneficial, and we’re showing here how it’s beneficial.”

Currently there are no effective treatments to promote neuronal survival and regeneration after central nervous system injury. Treatments for spinal injuries historically relied on immune suppression to prevent the collateral damage that results from the immune response, but growing evidence has shown that approach to be ineffective. The new findings suggest that doctors may instead want to increase the interleukin 4 response, to boost the protection it provides. They also may be able to determine how well a patient will respond to treatment by developing a test to detect the number of interleukin 4-producing cells present.

The discovery was the result of a collaboration between researchers in the U.S. and Germany. Their findings have been published online by the Journal of Clinical Investigation. The article’s authors are Walsh, Sven Hendrix, Francesco Boato, Igor Smirnov, Jingjing Zheng, John R. Lukens, Sachin Gadani, Daniel Hechler, Greta Gölz, Karen Rosenberger, Thomas Kammertöns, Johannes Vogt, Christine Vogelaar, Volker Siffrin, Ali Radjavi, Anthony Fernandez-Castaneda, Alban Gaultier, Ralf Gold, Thirumala-Devi Kanneganti, Robert Nitsch, Frauke Zipp and Kipnis.