WSU Applebaum Faculty Research Award Program (FRAP) recipients announced

After a two-year hiatus, the Wayne State Eugene Applebaum College of Pharmacy and Health Sciences Faculty Research Award Program (FRAP) has returned for the 2022-23 academic year. Faculty members Sara Lolar, Andrew Lipchik and Timothy Stemmler were selected to receive funding for their research proposals.

The FRAP committee was chaired by Associate Professor of Pharmacy Practice Kyle Burghardt.

"The proposals chosen stood out among a highly competitive field of applications. I am looking forward to learning the results of these timely and relevant studies, which are slated to be shared with the WSU Applebaum community at a future College Research Day," Burghardt said. "We are grateful to Dean Brian Cummings for prioritizing faculty research and bringing FRAP back to support it."

FRAP Junior Clinical Track Faculty Award: $10,000
For faculty with current appointments as assistant professor, clinical track who do not currently have an active award above $100,000 from external sources.

Sara LolarSara Lolar
Assistant Clinical Professor of Physician Assistant Studies

Title: Physician Assistant scholarship: gender differences and factors that promote female authorship

Abstract: Success in research and advancement in academic rank are well-known challenges in the physician assistant (PA) profession. The majority of academic PAs (53%) have never published a peer-reviewed article in their career and 61% do not advance beyond the rank of assistant professor. Because a successful track record of scholarship is historically required for academic advancement, it can be presumed lack of research productivity is a reason PA faculty struggle with advancement at their institutions.

The existence of gender differences in scholarly productivity, advancement in rank, and representation in leadership roles are well researched in medicine. Gender differences and barriers in the PA profession remain poorly understood. A persistent bias promoting men over women has been shown in PA salary and promotion, but less is known about gender differences in scholarship. Because there are proportionally more women in the professoriate (70.1%), it is imperative to understand the role gender plays in scholarship and address bias if it exists.

FRAP Junior Tenure Track Faculty Award: $10,000
For faculty with current appointments as Assistant Professor, Tenure Track who do not currently have an active award above $100,000 from external sources.

Andrew LipchikAndrew Lipchik
Assistant Professor of Pharmaceutical Sciences

Title: Development of a toleragenic Beta-cell targeted antibody for immune suppression

Abstract: Allogeneic islet transplantation or autologous stem-cell derived beta cells offer a promising treatment to exogenous insulin therapy for type 1 diabetes. However, islet graft rejection is a common due to allogenic and autoimmune responses from the recipient's immune system. Therefore, long-term immunosuppressive therapy is required to support islet engraftment following transplantation, but results in serious health consequences for the recipient. These toxic side effects are the result of nonspecific effects of the immunosuppressive regimens. Here, we propose to use an approach similar to antibody drug conjugates for targeted delivery and remodeling of the islet microenvironment. Remodeling the extracellular microenvironment has proven to be an effect strategy to activation the immune system for the treatment of cancer through the blockade of immune checkpoint.

Here, we will demonstration the specific delivery of the monomeric sialic acid polymer, polysialic acid, to beta cells to generate an anti-inflammatory microenvironment. We will leverage the pleiotropic effects of sialic acid on the immune system to protect the beta cells from both autoimmune and allogeneic immune responses. These effects will be tested in vitro during phase I using purified immune cell populations and in vivo during phase II using two mouse models of allogeneic islet transplantation. This proof-of-concept therapy will be the first demonstration of new paradigm in anti-inflammatory therapies and immunosuppression for the treatment and support of islet transplantation and engraftment.

FRAP Fast Track Research Award: $20,000
For faculty with any type of appointment who are interested in starting a new line of work that differs from their current research program and requires initial funding to support pilot studies for future grant submissions that align with the new area of investigation.

Tim StemmlerTimothy Stemmler
Professor of Pharmaceutical Sciences

Title: Demonstrating Therapeutic Efficacy in Treatment of Friedreich's Ataxia of Iron- Chelating, HIF-1 Activators Through Biophysical Analysis of Prolyl Dehydroxylase Drugs

Abstract: Friedreich's ataxia (FRDA), the most prevalent inherited neuromuscular disease, is a predominantly neurologically defined mitochondrial disorder. Many FRDA patients develop cardiomyopathy that reduces life expectancy to about 40 years, with morbidity due primarily to degradation of cardiac function. FRDA has no known effective treatment; supportive and palliative measures only are currently available for clinicians to treat FRDA. As a recessive genetic disorder, reduced expression of the mitochondrial iron chaperone frataxin (FXN) causes the disease, and this could be a target for genetic intervention. However, this potentially curative clinical practice is decades away, based on the current status of this approach, despite some success with in cellulo models. FXN deficiency and its mitochondrial localization makes FRDA a disease of the mitochondria and therefore, of energy degradation, as is the case with a broad spectrum of neurodegenerative disorders. Given the essential role played by FXN in mitochondrial iron metabolism, dysregulation of cell iron is commonly a focus of research on disease mechanisms as well as therapeutic intervention. To date, no FRDA drug has been approved for clinical use in this or any other spinocerebellar ataxia. The co-enzyme Q biomimetics ibedenone, and omaveloxolone are leading examples of these efforts; the latter has been granted a Fast Track designation by the FDA. However, omaveloxolone does not target dysregulation of mitochondrial iron trafficking and function, but rather activates oxidative stress pathways leaving fundamental cell morbidity untreated. A research plan that engages rational therapeutic platforms to provide new insight into molecular mechanisms of FRDA is therefore needed.

Toward this end, commercially available PBT434 was the lead in a successful Phase I trial for treatment of Multiple System Atrophy (MSA), a Parkinsonian disorder (by Alterity Therapeutics). A Phase 2 trial has now been approved (New Zealand Medsafe). In pre-clinical studies, PBT434 has robust antioxidant activity and suppresses a-synuclein-related neurotoxicity in MSA mouse models. The Kosman Lab has demonstrated PBT434 rapidly and reversibly diffuses across cell barriers, decreases cell iron uptake and stimulates iron efflux. Recent work by our lab shows 434 has a micro-molar specific affinity for Fe2+ and a cell-accessible reduction potential (320 mV) that supports labialization of cytoplasmic ferrous ions leading to an altered transcriptional and translational profile. Our goal in this report is to fully characterize and compare the metal binding characteristics of PBT434 with related drugs and then explore their targeted iron delivery to the cytosolic iron chaperone "PCBP" that delivers metal for iron-dependent hydroxylases activity and FXN based Fe-S cluster assembly. Instrumentation and procedures for Fe-drug and Fe-drug-protein interactions are already established in the Stemmler lab, and this represents a new direction in research for our group.

About us

The Eugene Applebaum College of Pharmacy and Health Sciences is built on more than 100 years of tradition and innovation in the heart of Detroit. We have grown deep roots in our city, harnessing its powerhouse hospital systems and community service organizations as vibrant, real-world training grounds for students, with an ongoing focus on social justice in health care. And our research at all levels - from undergraduates to veteran faculty members - translates into creative solutions for healthier communities.

Wayne State University is a premier urban research institution offering approximately 350 academic programs through 13 schools and colleges to more than 25,000 students.

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