David Auerbach’s interest in pursuing a scientific career began during a hockey game his first year of college, when a teammate — who turned out to be a chief medical examiner — asked Auerbach if he would like to observe a case.
Now Auerbach’s career is taking a major step forward with a two-year KL2 Mentored Career Development Program award from the University’s Clinical and Translational Science Institute. The two-year program designed to support the early career development of multidisciplinary scientists, helping them transition to an independent career as a clinical and translational investigator.
“It (award) has opened up many doors for me,” says Auerbach, including lead authorship of a recent paper in Neurology.
Auerbach, a senior instructor in the Department of Medicine/Aab Cardiovascular Research Institute, is taking a multisystem approach to understanding the mechanisms that cause electrical disturbances in both the hearts and brains of patients with genetic ion channel diseases. Ion channels, located in the plasma membrane of cells, are narrow tunnels that open and close at precise times to allow the flow of ions into or out of the cell, thus shaping the electrical activity in the heart and brain.
As a postdoc working with Lori Isom, a professsor at the University of Michigan, Auerbach demonstrated that people with severe genetic forms of epilepsy were at a higher risk not only of electrical disturbances in the brain, resulting in seizures, but also of electrical disturbances in the heart, causing arrhythmias.
In order to establish an independent line of research, Auerbach decided to approach the problem in reverse: are people with long QT syndrome — a classically studied genetic cardiac disease that causes arrhythmias — also at an increased risk of seizures?
He came to Rochester in 2014 specifically because of its research strengths in this area, including the opportunity to work with such experts as Arthur Moss, the Bradford Berk Distinguished Professor of Medicine; Robert Dirksen, the Lewis Pratt Ross Professor and chair of pharmacology and physiology; and Charles Lowenstein, chief of cardiology and director of the Aab Cardiovascular Research Institute.
The KL2 award is enabling him to take full advantage of those opportunities.
“As an undergraduate and graduate student, your training is very formalized: you are told ‘these are the courses you need to take; these are the expectations you must meet.’ Even as a postdoc, you need strong mentorship and help in guiding your research progress,” Auerbach notes. “But eventually you need to start developing your independent research direction. However, you don’t want to just jump out into the middle of this body of water without any direction.”
“Just writing the KL2 application forced me to really think about what are the critical pieces of my career development,” Auerbach said.
The KL2 award has provided the pieces, including:
1. A strong mentoring team whose members bring diverse areas of expertise that are well suited to the “multisystem” approach Auerbach is pursuing. The members include Moss, a renowned expert on cardiac arrhythmias and the genetics of heart disease; Dirksen, who specializes in the mechanisms of muscle diseases; Lowenstein, whose clinical interests include cardiac patients with acute coronary syndromes; and Robert Gross, professor of neurology, whose interests have centered on aspects of cellular neuropharmacology.
2. An individually designed training program of courses, seminars, and workshops to help Auerbach become well rounded. Trained in basic science, he is broadening his clinical knowledge with classes in database management and analysis, for example. Because his prior research was primarily focused on cardiac disturbances, he has taken EEG seminars to better understand neuronal symptoms.
3. An opportunity to develop preliminary data, using Moss’s Long QT Patient Registry and an animal model of the disorder. This has resulted in one NIH grant, an invitation to apply for another, the paper in Neurology and another in preparation.
All of this has “created an ideal environment,” Auerbach says, toward reaching his next goal: Securing a tenure track faculty position at the Medical Center.
‘We need to take the blinders off’
He is excited about the associations he is establishing between long QT syndrome, a classically studied heart disorder, and seizures resulting from electrical disturbances in the brain. “We need to take the blinders off. We need to look not just at the classic organ of study, but the multisystem manifestations of the disease,” Auerbach said.
He recently demonstrated that patients with long QT syndrome are also at an increased risk of seizures. Due to the great breadth of information in the Long QT Syndrome Registry, he was even able to tease out differences in the risk of seizures based upon the type of long QT syndrome and the region of the mutation in the protein structure.
In the paper published in Neurology, Auerbach showed a clear association between the heart and the brain of LQTS patients. Patients carrying LQTS genetic mutations were three times more likely to have experienced seizures in their past, compared to their family members who did not carry those mutations. Interestingly, LQTS patients who had a history of seizures also tended to have worse cardiac symptoms. (Read more here.)
“I’ve shown an association between long QT syndrome and seizures; now we need to understand the mechanisms underlying this, in order to really understand why these people are at an increased risk of both neural and cardiac diseases.”
The research plan in his CTSI-KL2 grant outlines a translational approach that will help him further his studies in that direction, including further epidemiological analyses, plus mechanistic cellular/animal studies.
