Seven projects funded through translational science pilot grant program

Penn State Clinical and Translational Science Institute generates innovative health research ideas and promotes collaboration through its Bridges to Translation pilot grant program, which seeks to link researchers not traditionally in health research with those who can help mold a new idea.

The institute recently funded seven diverse projects in Bridges to Translation V. These grants allow researchers to explore new ideas and gather information in preparation for more substantial grant opportunities from outside organizations.

After a competitive process, Bridges to Translation V grants were awarded to principal investigators Winnie Adebayo and Cara Exten; Amy Arnold; Nikolay Dokholyan; Michael Hayes and Susan Veldheer; Charleen Hsuan; Dahlia Mukherjee; and Jane Schubart and Rebecca Bascom. The projects are:

Barriers to health care in rural transgender adults

Winnie Adebayo and Cara Exten are studying the barriers to health care and the unmet health needs of rural transgender adults.

“The overall goal of this research is to identify the barriers transgender individuals are experiencing to seeking and receiving health care,” Exten said. “Results from this study will allow us to identify critical points of intervention. We plan to disseminate results to health care providers, clinics and trainers of health care providers to inform and educate about the barriers. We intend to use these results to aid in the development of intervention programming to reduce health care barriers affecting this vulnerable population.”

Collaboration is vital for the project, Adebayo said.

“We will be working closely with co-investigators Carly Smith and Katharine Dalke from the College of Medicine, and Julie Barroso, a mixed-methods expert from the Medical University of South Carolina,” Adebayo said. “We will also collaborate with Penn State Center for Sexual and Gender Diversity and clinics and community-based organizations that serve transgender populations across the state of Pennsylvania.”

Adebayo and Exten are both assistant professors of nursing.

Understanding ‘brain fog’ in postural tachycardia syndrome

Amy Arnold is studying the disabling disorder postural tachycardia syndrome. The disease causes an excessive increase in heart rate upon standing that is accompanied by symptoms such as dizziness and fatigue.

“One of the most underappreciated and bothersome symptoms of this syndrome is impaired cognition or ‘brain fog,’ which occurs to a level that interferes with daily activities such as work and education,” Arnold said. “However, the reasons why patients have problems with cognition are not well understood. This project will determine if brain activity in response to mental tasks is different in postural tachycardia syndrome patients compared with healthy subjects when at rest and during a physical challenge that mimics standing.”

A better understanding of the causes of this “brain fog” can lead to new treatments to improve symptoms. The findings from this project may also have broader importance to improve understanding of brain mechanisms involved in standing in healthy individuals and patients with other cardiovascular disorders.

This study will collaborate with four College of Medicine departments, including experts in cardiology, cardiovascular autonomic disorders including postural tachycardia syndrome, brain imaging modalities, cognitive neuroscience and neuropsychological testing.

Arnold is an assistant professor of neural and behavioral sciences.

Speeding up drug discovery

Nikolay Dokholyan is studying the use of software algorithms to speed up drug discovery.

“Drug discovery is a costly and long process: a drug discovery process can take over a decade and cost several billion dollars,” Dokholyan said. “One of the primary time and money consuming steps is the identification of potential lead compounds that would be further tested in animals and clinic.”

Dokholyan and his collaborators created software called MedusaDock, which helps screen potential compounds by taking into account the complex physical and chemical interactions between small molecules and proteins. Many drugs are small molecules. This process can be slow, even using computer software.

Dokholyan teamed up with Mahmut Kandemir and Kamesh Madduri, both from the School of Electrical Engineering and Computer Science, graduate student Mengran Fan and postdoctoral fellow Jian Wang to accelerate the algorithms.

“We came up with the plan to port our software to graphical processor units – also called GPUs – which would allow calculations to be massively parallel,” Dokholyan said. “GPUs are now in high demand for their ability to process a large number of simple mathematical operations and have been the centerpiece for mining bitcoins. We plan to utilize GPUs to increase the speed and processing power of MedusaDock. This proposal is a harmony of very distinct but complementary expertise. Neither of the sides would have been able to achieve the goals without working together.”

To further improve the speed, the team also decided to first predict potential binding sites before performing more expensive simulations. Dokholyan believes that through these efforts, time for each attempt will decrease from up to eight minutes to less than a minute.

Dokholyan is G. Thomas Passananti Professor and vice chair for research in the Department of Pharmacology and a professor of biochemistry and molecular biology.

Barriers to sharing social influence information

Michael Hayes and Susan Veldheer are studying what gets in the way of patients and their care providers sharing information about social influences that affect health.

“Some evidence suggests as much as 40 percent of health outcomes are determined by social influences, such as the conditions in the places where people live, learn, work and play,” Hayes said. “With safe, acceptable and effective ways to use information about social influences, patients will receive better care and achieve greater health.”

The project will provide essential data to identify barriers to and solutions that enable the routine collection of such information as the standard of patient care.

“Collaboration is critically important and lies at the heart of our pilot project,” Veldheer said. “We will do this through a series of Clinical and Translational Science Institute-conducted Community Engagement Studios and research-team led focus group meetings. There will also be ongoing collaboration among the pilot’s team of investigators and a related project led by Dr. Hayes and Dr. Andrea Hobkirk – a Penn State Cancer Institute Catchment Area Award that also aims to investigate social influences on health.”

Hayes is an assistant professor of psychiatry and Veldheer is an assistant professor of family and community medicine.

Laws regulating inter-hospital transfers

Charleen Hsuan will examine state laws regulating inter-hospital transfers, disparities in quality of emergency department transfers, and the association of one state law on transfers.

“The Emergency Medical Treatment and Labor Act requires Medicare-participating hospitals to provide emergency care to all patients, regardless of insurance status, race or ethnicity, and permits transfers of unstable patients with emergency medical conditions only under specified conditions,” Hsuan said. “This law enshrines the belief, recommended by the Institute of Medicine, that improving health care quality requires that care be equitable. However, hospitals continue to violate the law, including the transfer provision. This leaves a large potential for state laws to decrease disparities in hospital transfers.”

This project also serves as a pilot project for the institute’s policy impact core. The core’s work is related to T3, translation to practice, and T4, translation to population health, in the phases of translational science.

“Evidence-based policies such as transfer guidelines for hospitalized patients have the potential to affect public health, but only to the extent that they are used,” Hsuan said. “Laws are an important mediator of the relationship between the research that creates the guidelines and their public health effects, as they influence what providers do and thus what care patients receive.”

The project has collaborators from Health Policy and Administration and College of Health and Human Development at University Park and Public Health Sciences and Emergency Medicine at the College of Medicine.

Hsuan is an assistant professor of health policy and administration.

Study of major depressive disorder

Dahlia Mukherjee is studying the loss of interest or pleasure in activities that a person usually enjoys when they have major depressive disorder. This loss is called anhedonia and is linked to a responding poorly to treatment or having thoughts to self-harm.

“Current treatments for depression primarily focus on treating depressed mood and not anhedonia,” Mukherjee said. “Part of the reason why anhedonia is not addressed in treatment is that it is not well understood.”

Mukherjee’s project will look at changes in brain activation and inflammation levels in depressed people reporting high anhedonia. Understanding these biological changes can lead to better treatment options.

Mukherjee is collaborating with Charles Geier, who will analyze the brain imaging results;

Brandon Auer and Christopher Engeland, who will process and analyze samples; and Erika Saunders, who will help with patient recruitment and medication management of patients.

“I am very excited to be working with such an accomplished and talented group of people,” Mukherjee said. “Hopefully, with the support of this pilot grant, my colleagues and I will be able to determine clues to a better understanding of anhedonia.”

Mukherjee is an assistant professor of psychiatry.

Educating primary care doctors to help patients with a rare disease

Jane Schubart and Rebecca Bascom are studying Ehlers-Danlos Syndromes, a set of rare heritable disorders of connective tissue.

They will study the effectiveness of using Project ECHO for Ehlers-Danlos Syndromes. Project ECHO at Penn State College of Medicine offers a unique learning experience and support network. ECHO, which stands for Extension for Community Healthcare Outcomes, gives primary care physicians the tools they need and a professional network to treat patients in regions with little or no access to specialists. It links expert specialist teams at an academic ‘hub’ with primary care clinicians in local communities – the ‘spokes’ of the model. Together, they participate in weekly virtual clinics, combined with mentoring and patient case presentations.

“People with Ehlers-Danlos Syndromes are a vulnerable group who are falling through the cracks in our health care system,” Schubart said. “Primary care physicians with expertise in treating Ehlers-Danlos Syndromes are difficult to find and specialists have waiting lists of two-to-three years.”

Researchers will evaluate both the program implementation and its performance to determine whether the program will increase quality and access to Ehlers-Danlos Syndromes specialty care.

“The support of the Clinical and Translational Science Institute has been essential and has made possible our growing portfolio of collaborative research,” Schubart said

Schubart is an associate professor of surgery, medicine and public health sciences and Bascom is a professor of medicine.

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