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Urinary immune cell profiling in sepsis-associated acute kidney injury

Alexander Flannery, PharmD, PhD, FCCM, BCCCP, BCPS
Assistant Professor, Pharmacy Practice and Science (College of Pharmacy)
Clinical Research Catalysts (CRC) Pilot Award, July 2021 - present

Up to 50% of cases of acute kidney injury (AKI) are attributed to sepsis, which is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Combining their expertise in sepsis-AKI research and immunology, Drs. Flannery and Feola are collaborating to characterize the urinary immune cell profile as it evolves over time in patients with sepsis-associated AKI to better understand the potential role of various immune cells in kidney injury and repair, particularly macrophages. Additionally, the pilot will allow them to refine techniques to study gene expression at the single cell level with scRNA-seq technology. Together, these studies will use non-invasive urine samples to forge an improved understanding of the immunobiology in various stages of kidney injury and repair due to sepsis.

Co-PI: David Feola, PharmD, PhD (Pharmacy Practice and Science)

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Mechanistic and pharmacologic studies of selective mithramycin analogues targeting EWS-FLI1 in Ewing sarcoma

Markos Leggas, PhD
Professor, Pharmaceutical Science (College of Pharmacy)
Markey Run for the Roses Award, January 2021 - present

Ewing sarcoma family of tumors (ESFT) is a family of resilient devastating cancers of bone and soft tissue affecting primarily children and young adults. Current highly cytotoxic combination therapy of five drugs provides only 30% overall survival. The goal of this project is to gain molecular insights into the mode of action of MTM via structural, biochemical and pharmacological studies to generate a highly efficacious and selective anti-ESFT treatment. The Markey Run for the Roses Award is a one-time 10% match of the YR1 direct costs (up to $40K) for a new multi-PI NCI R01 grant.

Co-PIs: Jurgen Rohr, PhD (Pharmaceutical Sciences); Oleg Tsodikov, PhD (Pharmaceutical Sciences)

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Anti-inflammatory and gingival absorption properties of a new mPGES-1 inhibitor

Octavio Gonzalez, DDS, MS, PhD
Associate Professor, College of Dentistry
Igniting Research Collaborations (IRC) Pilot, January 2021 - present

Periodontal disease is a chronic inflammatory disease that, if not treated, leads to local (i.e., tooth loss) and systemic effects (increased risk for cardiovascular disease, poor diabetes control, and Alzheimer’s disease). Microsomal prostaglandin E synthase-1 (mPGES-1) is known as a promising target for development of a next generation of anti-inflammatory drugs. Through structure-based de novo drug design, the Zhan Lab has designed and discovered a novel type of potent and highly selective mPGES-1 inhibitors targeting the conserved region of the active site that are suitable for preclinical studies. In this pilot, the Gonzalez lab will evaluate the potential of a novel, potent and highly selective mPGES-1 inhibitor in treatment of periodontitis and the Zhan lab will conduct inflammatory biomarker analysis.

Co-PIs: Chang-Guo Zhan, PhD (Pharmaceutical Sciences)

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Opioid prescribing in dentistry: Building and implementing a framework to nudge provider behavior

Douglas Oyler, PharmD
Assistant Professor, Pharmacy Practice & Science (College of Pharmacy)
Igniting Research Collaborations (IRC) Pilot, January 2021 - present

This project aims to evaluate patient- and provider-specific factors related to opioid prescriptions after dental extractions through medical record analysis and qualitative interviews with prescribers. Additionally, the project will use state-level prescription drug monitoring program data to build a framework for evaluation of future electronic medical record interventions to address opioid prescribing in dentistry. This collaboration leverages expertise from Dentistry, Medical Informatics, Public Health, Behavioral Science, and Opioid Safety to address an ongoing public health concern in Kentucky.

Co-PIs: Marcia Rojas-Ramirez, PhD (College of Dentistry), Hilary Surratt, PhD (Behavior Science, College of Medicine), Dana Quesinberry, JD, DrPH (KIPRC, College of Public Health), Philip Bernard, MD (Pediatrics, College of Medicine), Craig Miller, DDS, MS (Oral Diagnosis, College of Dentistry)

doug oyler standing in lobby with arms crossed

Cognitive reserve and driving mobility

Caitlin Pope, PhD
Assistant Professor, Department of Health, Behavior & Society (College of Public Health)
Igniting Research Collaborations (IRC) Pilot, January 2021 - present

In the United States, Alzheimer’s disease and related dementias (ADRD) are the 5th leading cause of death for adults 65 and older and are estimated to affect approximately 13.8 million adults in 2050. One proposed mechanism of maintaining cognitive abilities in the face of brain neuropathology over time is cognitive reserve. To date, there is a lack of research on cognitive reserve and functional abilities such as driving mobility and if any differences seen in driving mobility in early stages of cognitive impairment can be attributed to cognitive reserve. This project will examine the association between cognitive reserve and driving mobility in older adult drivers across a continuum of cognitive impairment.

Co-PIs: Daniela Moga, MD, PhD (Pharmacy Practice & Science); Yang Jiang, PhD (Behavioral Neuroscience, College of Medicine)

Older Woman Driving a Car

A study of macrophage gene expression in sarcoidosis and the effect of azithromycin derivatives

Parijat Sen, MD
Assistant Professor, Internal Medicine (College of Medicine)
Igniting Research Collaborations (IRC) and COBRE for Translational Chemical Biology co-Pilot, January 2021 - present

Sarcoidosis is a multi systemic granulomatous inflammatory condition affecting more than 200,000 Americans and many more globally. Due to a lack of clear understanding of the involved immune pathways, current therapies are mostly limited to various systemic immunosuppressive agents. This project aims to explore the effect of azithromycin, an FDA-approved antibiotic with immunomodulatory properties, on gene expression in macrophages (a predominant inflammatory cell forming sarcoid granulomas) through transcriptomic assays. The pilot also aims to explore a library of synthetic derivatives of azithromycin to try and identify compounds which retain the immunomodulatory effect on macrophages but lack antimicrobial properties. This project involves a diverse team with expertise in clinical care of sarcoidosis, immunology and biosynthetic molecular development to identify novel targets and molecules for sarcoid therapy.

Co-PIs: David Feola, PhD, PharmD (Pharmacy Practice & Science); Jamie Sturgill, PhD (Internal Medicine, College of Medicine), Steven Van Lanen, PhD (Pharmaceutical Sciences)

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Early reduction of Post-Operative Pain and inflammation to Expedite Return to function after KNEE arthroscopy (PROPER KNEE trial)

Austin Stone, MD PhD
Assistant Professor, Orthopaedic Surgery (College of Medicine)
Igniting Research Collaborations (IRC) Pilot, January 2021 - present

Meniscus tears requiring surgery occur in 15% of Americans ages 10-65 years, which makes arthroscopic meniscal procedures the most commonly performed orthopaedic surgery in both civilian and military populations. It is common to use an opioid drug for post-operative pain relief. Through development and use of a unique drug repurposing approach, called DREAM-in-CDM (Drug Repurposing Effort Applying Integrated Modeling-in vitro/vivo-Clinical Data Mining), the Zhan Lab has identified a potent mPGES-1 inhibitor (targeting the open conformation of mPGES-1 predicted computationally) among existing FDA-approved non-opioid drugs. In this project, a pilot clinical trial will be conducted by a very talent multidisciplinary team to test the efficacy of the non-opioid drug in treatment of post-operative pain.

Co-PIs: Chang-Guo Zhan, PhD (Pharmaceutical Sciences); Lauren Whitehurst, PhD (Psychology, College of Arts & Sciences), Cale Jacobs, PhD (Orthopaedic Surgery, College of Medicine), Nicole Cascia, PhD, CES (Orthopaedic Surgery, College of Medicine)

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Novel mith-platin conjugates for treatment of platinum-complex resistant ovarian cancers

Jill Kolesar, PharmD, MS, FCCP, BCPS
Professor, Department of Pharmacy Practice & Science
Inter-Departmental Collaboration (IDC) Pilot, July 2019 - present

More than 20,000 women will be diagnosed with, and approximately 14,000 will die of, ovarian cancer in 2021. To address this unmet medical need, Drs Kolesar, Rohr and Tsodikov are working together to develop new medications for treating ovarian cancer, mithplatins. Mithplatins overcome common resistance mechanisms in ovarian cancer and will be synthesized, tested for DNA binding and damaging capabilities and evaluated in preclinical models. This highly innovative work introduces an entirely novel class of compounds that are both clinically relevant and mechanistically important, providing key insights into the action of mithplatins on DNA binding and repair.

Co-PIs: Jurgen Rohr, PhD (Pharmaceutical Sciences); Oleg Tsodikov, PhD (Pharmaceutical Sciences

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We wish to remember and honor those who inhabited this Commonwealth before the arrival of the Europeans. Briefly occupying these lands were the Osage, Wyndott tribe, and Miami peoples. The Adena and Hopewell peoples, who are recognized by the naming of the time period in which they resided here, were here more permanently. Some of their mounds remain in the Lexington area, including at UK’s Adena Park.

In more recent years, the Cherokee occupied southeast Kentucky, the Yuchi southwest Kentucky, the Chickasaw extreme western Kentucky and the Shawnee central Kentucky including what is now the city of Lexington. The Shawnee left when colonization pushed through the Appalachian Mountains. Lower Shawnee Town ceremonial grounds are still visible in Greenup County.

We honor the first inhabitants who were here, respect their culture, and acknowledge the presence of their descendants who are here today in all walks of life including fellow pharmacists and healthcare professionals.