AHA Grants Will Accelerate Search for New Stroke Therapies
Wednesday, June 27, 2018
A series of awards from the American Heart Association (AHA) to a team of researchers at the University of Rochester Medical Center (URMC) will focus on the development of new treatments to thwart the damage in the brain caused by stroke.
One of the research projects brings together experts in stroke, cardiovascular biology, platelet biology, and peptide chemistry. Marc Halterman, M.D., Ph.D., with the URMC Center for Neurotherapeutics Discovery, Scott Cameron, M.D., Ph.D., and Craig Morrell, D.V.M., Ph.D., with the URMC Aab Cardiovascular Research Institute, and Bradley Nilsson, Ph.D., with the University of Rochester Department of Chemistry will focus on the role that platelets play in acute brain injury and inflammation during stroke.
Platelets serve an important role in protecting against blood loss and repairing injured blood vessels. However, during a stroke the inflammatory properties of platelets can interfere with the restoration of blood flow once the clot in the brain is removed, particularly in micro-vessels, which can lead to permanent damage of brain tissue.
The research team will build synthetic peptides that activate platelets to study the phenomenon – which is called no-reflow – in an effort to identify specific switches within platelets that can be turned off and limit the cells’ inflammatory functions without blocking their ability to prevent bleeding.
Two AHA pre-doctoral fellowship awards Kathleen Gates and Jonathan Bartko in Halterman’s lab will support research that examines the link between an immune system response triggered by stroke in the lungs that can exacerbate damage in the brain and investigate the cellular mechanisms that determine whether or not brain cells die following stroke.
A final AHA award to the Halterman lab will seek to identify new drug targets by focusing on specific proteins activated during stroke that are suspected to play an important role in determining the survival of neurons.
Collectively, the AHA Collaborative Sciences Award, Pre-Doctoral, and Innovation awards represent $1.09 million in funding.Read More: AHA Grants Will Accelerate Search for New Stroke Therapies
Catching Research Fever: UR CTSI’s Academic Research Track Turns Medical Students into Medical Researchers
Wednesday, May 16, 2018
By Susanne Pritchard Pallo
The MSTP 2017 incoming class, with former UR CTSI Academic Research Track participants Samuel Weisenthal and Ian De Andrea-Lazarus (far right).
Over the past several decades, concerns have risen about the declining population of physician-scientists, with reports pointing to early career training and support as a possible solution. The UR CTSI Academic Research Track, which allows medical students to try their hands at research, has helped two University of Rochester School of Medicine and Dentistry students take the next step toward a research career: joining an MD-PhD program.
The pair, Ian De Andrea-Lazarus and Samuel Weisenthal, joined the University of Rochester Medical Scientist Training Program after finishing their Academic Research Track projects. This is a move that a new study from the Association of American Medical Colleges suggests will help them stay in science. The study tracked MD-PhD program graduates over 50 years and showed that most stuck with their research careers.
Ian and Sam explain what drove them to pursue a career as physician-scientists.
Why did you join the UR CTSI’s Academic Research Track?
Ian: I’ve always craved knowledge and enjoy the challenge of pushing the boundaries of existing human knowledge. I had several years of research experience before applying for medical school - as an undergraduate research assistant in the Linguistics Department at Gallaudet University and as a post-baccalaureate fellow at the National Cancer Institute. For two years, I worked in the Laboratory of Cancer Biology and Genetics at NCI, studying a non-selective cation channel found mainly in the peripheral nervous system that is involved in the transmission and modulation of pain.
Sam: Like Ian, I was inspired by my time as a post-baccalaureate trainee at the NIH, where I worked for a year in a computational radiology lab. I also had a great time doing a summer research project in health informatics at Rochester. I joined the Academic Research Track because I wanted to study the vast amount of data being collected through the electronic health record. In a single year, the University of Rochester Medical Center alone accrues more than two terabytes of non-image data (a lot). I was particularly interested in how this data could be used to predict – and hopefully help prevent – adverse health events in patients.
How did your experience in the Academic Research Track drive you to join the University of Rochester Medical Scientist Training Program?
Ian: I had originally wanted to apply for the University of Rochester Medical Scientist Training Program but I was afraid that my application would not be competitive enough. The Academic Research Track was the bridge that allowed me to pursue my goal of becoming a physician-scientist and reinvigorated my interest in research. The program allowed me to obtain a master’s degree in Public Health along with the tools and drive I needed to apply for the MD-PhD program.
Sam: I had also previously considered an MD-PhD program, but did not have a cohesive story to tell in an application. The Academic Research Track year allowed me to obtain a master’s degree in Data Science from the Goergen Institute for Data Science at the University of Rochester, which provided a foundation for more advanced study. It also helped me discover the UR CTSI’s Translational Biomedical Science PhD Program, which was a good fit, and to fully engage in a research project in a great lab.
What did you study during the Academic Research Track program?
Sam: We were initially interested in predicting readmission to the intensive care unit, which is a quality metric used by some hospitals. Ultimately, however, we decided to focus on predicting acute kidney injury, which is common, deadly, and sometimes completely preventable with simple interventions like fluid administration or medication review. Insights from our studies could be used to hopefully develop a better predictive tool that could help prevent acute kidney injury in the future.
Ian: We explored the association between low levels of lead in the serum of 3- to 5-year-old children and their mental capacity to focus attention, remember instructions, and juggle multiple tasks. We used a well-characterized tool for assessing these mental executive functions in children, called the Stroop day-night task, but found that the tool may not be sensitive enough to detect lead’s effects on neurodevelopment.
What are you studying now?
Sam: I am pursuing a joint degree between the Translational Biomedical Science PhD Program and Computer Science Department, with Computer Science as a minor. This includes select coursework in computer science, biostatistics, and medicine. My research focus is a continuation of my Academic Research Track project with Martin Zand, Ph.D., co-director of the UR CTSI and professor of Nephrology and Public Health Sciences at the University of Rochester Medical Center. Our goal is to improve acute kidney injury prediction by reformulating the standard approach and performing more rigorous error analysis. Ultimately, we hope to squeeze maximal predictive value out of electronic health record data to assist physicians in making the best decisions for at-risk patients.
Ian: I am pursuing a doctoral degree in the UR CTSI’s Translational Biomedical Science PhD Program and working with John Foxe, Ph.D., Killian J. and Caroline F. Schmitt chair of Neuroscience, and Edward Freedman, Ph.D., associate professor of Neuroscience, on a mobile brain/body imaging (MoBI) study. We are interested in understanding how the brains of people with decreased cognitive function, like those with Alzheimer’s disease, handle the cognitive demands of multitasking while walking, which requires continuous processing of information about the environment and body position.
Read More: Catching Research Fever: UR CTSI’s Academic Research Track Turns Medical Students into Medical Researchers
Lungs Mays Hold Key to Thwarting Brain Damage after a Stroke
Wednesday, January 31, 2018
By Mark Michaud
The harm caused by a stroke can be exacerbated when immune cells rush to the brain an inadvertently make the situation worse. Researchers at the University of Rochester Medical Center (URMC) are studying new ways to head off this second wave of brain damage by using the lungs to moderate the immune system’s response.
“It has become increasingly clear that lungs serve as an important regulator of the body’s immune system and could serve as a target for therapies that can mitigate the secondary damage that occurs in stroke,” said URMC neurologist Marc Halterman, M.D., Ph.D. “We are exploring a number of drugs that could help suppress the immune response during these non-infection events and provide protection to the brain and other organs.”
Halterman’s lab, which is part of the Center for NeuroTherapeutics Discovery, has been investigating domino effect that occurs after cardiac arrest. When blood circulation is interrupted, the integrity of our intestines becomes compromised, releasing bacteria that reside in the gut into the blood stream. This prompts a massive immune response which can cause systemic inflammation, making a bad situation worse.
While looking at mouse models of stroke, his lab observed that a similar phenomenon occurs. During a stroke blood vessels in the brain leak and the proteins that comprise the wreckage of damaged neurons and glia cells in the brain make their way into blood stream. The immune system, which is not used to seeing these proteins in circulation, responds to these damage-associated molecular patterns and ramps up to respond. Mobilized immune cells make their way into the brain and, finding no infection, nevertheless trigger inflammation and attack healthy tissue, compounding the damage.
The culprit in this system-wide immune response is neutrophils, a white cell in the blood system that serves as the shock troops of the body’s immune system. Because our entire blood supply constantly circulates through the lungs, the organ serves as an important way station for neutrophils. It is here that the cells are often primed and instructed to go search for new infections. The activated neutrophils can also cause inflammation in the lungs, which Halterman suspects may be mistakenly identified as post-stroke pneumonia. The damage caused by activated neutrophils can also spread to other organs including the kidneys, and liver.Read More: Lungs Mays Hold Key to Thwarting Brain Damage after a Stroke
Andrew Cox Receives US Patent
Tuesday, January 30, 2018
MD/PhD student, Andrew Cox has been awarded a patent, "Attenuated Influenza Vaccines and Uses Thereof" (9,787,032), for a new live flu vaccine that is safer than the current one so should permit higher dose administration to overcome the current problems with the live vaccine.
When not in medical school, Andrew is currently pursuing his degree in the Dewhurst lab, working on temperature sensitivity of Influenza polymerase as a determinant of pathogenicity.