News

Jimmy Zhang, graduate student in the laboratory of Dr. Paul Brookes was awarded a two-year American Heart Association predoctoral fellowship entitled, “The Development of Novel Acute Myocardial Infarction Therapeutics Using Metabolomics and High-Throughput Screening” beginning January 1, 2017.

Project Summary:
Paradoxically, current AMI therapies have the common goal of promoting reperfusion and, in doing so, trigger events that lead to cell death. As a result, there is a need for new therapeutics that limit reperfusion-induced injury. Many of the pathologic cellular events of reperfusion-induced injury can be attributed to maladaptive metabolic remodeling. One particular metabolite of interest is succinate, which accumulates during ischemia. Upon reperfusion, succinate is consumed in the electron transport chain by Complex II, generating reactive oxygen species at Complex I. This reverse electron transport (RET) appears to be a major contributor to IR injury. Yet, despite the relevance of RET to IR injury, the pathway of succinate accumulation has yet to be elucidated. Additionally, succinate accumulation during ischemia might contribute to the generation of the mitochondrial membrane potential by permitting Complex I activity. This membrane potential can then be used for functions such as membrane transport and maintenance of redox status. In our preliminary data, nornicotine was identified as a potentially cardioprotective candidate, and was shown to inhibit Complex I activity. Inhibition of RET could be the mechanism of protection by nornicotine. Using high-throughput screening and metabolomic approaches, this project will determine whether inhibition of RET is a rapid metabolic adaptation that is conserved across cardioprotective strategies (nornicotine treatment, ischemic preconditioning, and ischemic postconditioning). Finally, the pathway and function of succinate accumulation will be investigated by measuring membrane potential and redox status in isolated mitochondria. Overall, this project aims to investigate RET in IR injury with the goal of developing novel therapeutics for AMI.

Diane Dalecki, Ph.D. (BME) and Denise C. Hocking, Ph.D. (Pharmacology and Physiology) received funding from the UR Technology Development Fund for their project titled “Ultra-collagen for enhanced wound healing”. The project aims to advance an ultrasound-based technology to direct collagen fiber microstructure and enhance the bioactivity of collagen hydrogels. Applications of this technology include fabrication of collagen-based wound dressings that promote healing of chronic wounds.

Suzanne N. Haber, Ph.D., has been awarded a NIH R13 Conference grant. On October 11-13, 2016, the University of Rochester Institute of Neuromedicine and the Silvio O. Conte Center will hold a meeting entitled “Persistent, maladaptive behaviors: why we make bad choices”. The program is designed to involve basic and clinical scientists with a specific focus on the fundamental elements that drive basic behaviors and action plans (reward, fear, and value assignment); circuit dysfunctions that underlie abnormalities in diseases with persistent, habit-like behaviors, despite some awareness that these behaviors are maladaptive; the circuit components that are common amongst diseases; computational approaches to understanding these circuits; and therapeutic approaches that effect these circuits.

Christopher Farrar, a Ph.D. candidate in the lab of Professor Denise Hocking, has been awarded a Ruth L. Kirschstein National Research Service Award (NIH-NRSA) Individual Predoctoral Fellowship (F31) from the National Heart, Lung, and Blood Institute for his project entitled “Influence of Extracellular Matrix Fibronectin on Platelet-Derived Growth Factor (PDGF) Signaling”. PDGF is produced by a variety of different cell types and stimulates mesenchymal cell proliferation, migration, and gene expression. Together with fibronectin, PDGF plays an important role in angiogenesis and wound repair. In contrast, excess PDGF and abnormal fibronectin matrix deposition are linked to several diseases, including pulmonary fibrosis, atherosclerosis, and certain cancers. The focus of Chris’ project is to determine how mesenchymal cell adhesion to extracellular matrix fibronectin fibrils influences the ability of these cells to respond to PDGF, with the long-term goal of developing new treatment approaches to effectively regulate the sensitivity of cells to growth factor stimulation.

David Auerbach, senior instructor in medicine,
says his KL2 award has "opened many doors for me."

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-yearKL2 Mentored Career Development Program award from the University's Clinical and Translational Science Institute.

"It 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 professor 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.

Sarah R. Heilbronner, PhD, will receive the Postdoctoral Achievement Award at the 2016 Convocation, on September 8. She is currently a postdoc in Dr. Suzanne Haber's lab, where she is studying the neural circuitry associated with reward processing, decision-making, and executive function.

Along with the other members of Dr. Haber's team, Sarah is working to determine the anatomical connections that are affected by neurosurgical interventions for psychiatric disorders (such as deep brain stimulation).

Professor David I. Yule, Ph.D., will also receive the Faculty Teaching Award, specifically the Trainee Academic Mentoring Award in Basic Science, as well as the Louis C. Lasagna Endowed Professorship at convocation. The Yule Lab studies intracellular calcium signaling in cells which are typically, electrically non-excitable. In cells such as the liver, exocrine, pancreas, salivary glands and various cells in the blood, increases in intracellular calcium are fundamentally important for diverse processes including secretion of digestive enzymes and fluid, glucose metabolism together with cellular growth and differentiation.

Congrats Sarah and David!

David Yule

David Yule, professor of pharmacology and physiology, has been appointed the Louis C. Lasagna Professor in Experimental Therapeutics for five years, effective July 1. He retains his joint appointments as professor of medicine and as professor in the Center for Oral Biology.

For the past 15 years, Yule has studied calcium’s role in disorders in which calcium signaling and secretions are disrupted, such as Sjögren’s syndrome—in which patients experience dry mouth due to a lack of saliva—and acute pancreatitis.

Using state-of-the art imaging and electrophysiological techniques, Yule’s lab monitors calcium signals to achieve a better understanding of the mechanisms that underlie these signals with the goal that the studies will give insight into the control of important physiological processes in both normal physiology and disease states.

• Learn more about Yule’s research and lab

Yule received his PhD in physiology from the University of Liverpool in the United Kingdom. His research has been published in numerous journals, including the Journal of Biological Chemistry, Proceedings of the National Academy of Sciences, Science Signaling, and the Journal of Physiology. Yule serves on the editorial board for Gastroenterology, the preeminent journal in the field of gastrointestinal disease.

The Lasagna professorship honors Louis Lasagna, who served as chair of the Department for Pharmacology from 1970 to 1983, and brought the department to national recognition as a center of training and research. Lasagna, who was known for pioneering the study of placebos and writing an alternative Hippocratic oath, died in 2003.

The salivary gland secretes saliva that helps us chew and swallow the food we eat. The pancreas secretes digestive juices that enable our bodies to break down the fat, protein, and carbohydrates in the food. Secretions like these are important in countless activities that keep our bodies running day and night. A study published today in the journal Science Signaling uncovers a previously mysterious process that makes these secretions possible.

At the heart of the new study is calcium, which is present in all of our cells and is a gatekeeper of sorts: an increase in calcium in our cells opens up “gates” or “channels” that are required for the production and secretion of fluids like saliva. If calcium doesn’t increase inside cells the gates won’t open, a problem that occurs in diseases like Sjögren’s syndrome. Sjögren’s patients experience dry mouth due to a lack of saliva and have difficulty chewing, swallowing, and speaking, which severely hampers quality of life.

For the past 15 years David I. Yule, Ph.D., professor in the department of Pharmacology and Physiology at the University of Rochester School of Medicine and Dentistry has studied calcium’s role in Sjögren’s and other disorders in which calcium and secretions are disrupted, like acute pancreatitis. In the new study he answers an important question that has stumped scientists for years: what does it take for a particularly important calcium channel to open and start these processes?