Congratulations to the faculty in the UF College of Pharmacy who received research awards in July and August 2023.
Principal Investigator and Multiple Principal Investigator Awards
Dr. Jay McLaughlin was awarded a five-year R01 with approximately $500,000 coming to UF. Injection drug use increases the likelihood of contracting HIV, and opioid drug abuse and HIV have long been described as interrelated epidemics. In this new R01 (DA057884), MPI, Dr. McLaughlin will collaborate with Dr. Nazira El-Hage of FIU to analyze the autophagic function of the protein Beclin1 in reward behaviors induced by repeated exposure to morphine alone and in combination with EcoHIV, examining how the autophagy process regulates behavioral addiction and viral infection.
Opiates continue to be useful pharmacotherapies for treatment of pain, but suffer from severe side effects that has led to an epidemic in America. Over the last four years of this new R01 (DA057790), MPI Dr. Jay McLaughlin will collaborate with a research team led by Dr. Susruta Majumdar of Washington University on the development of safe, effective and well-tolerated pain medications without side effects by targeting delta opioid receptors based on new insights of receptor activity. The resultant compounds are hoped to improve both quality and length of life of patients in chronic pain.”
Dr. Jane Aldrich was awarded $150,000 from the Parkinson’s Foundation with Co-I Dr. Paramita Chakrabarty in the department of neuroscience. The project titled “Exploration of compounds that target alpha-synuclein phosphorylation,” to evaluate the lead compound in mouse models of aSyn pathology to demonstrate that it can modulate PP2A and aSyn, and to screen analogs of the lead compound in a cellular model to identify compounds with enhanced potency to modulate PP2A and decrease aSyn phosphorylation.
Dr. Chenglong Li received an award from the U.S. Department of Defense for two years of funding totaling $478,000 for a project titled, “Developing YAP/TEAD Inhibitors for Novel Nash-Associated Hepatocellular Carcinoma Therapeutics.” Along with partnering PI Dr. Pi at Tulane University, the project aims to optimize a protein-protein interaction inhibitor lead compound into drug-like small molecule with in vivo efficacy for potential targeted anti-cancer therapy. The Hippo signaling pathway normally controls organ size. However, if dysregulated, it would result in tumorigenesis and drug resistance. If successful, these compounds could be developed into a new class of drugs targeting the transcription engine in this oncogenic pathway.
Drs. Jürgen Bulitta (MPI), Günther Hochhaus (MPI) and Rodrigo Cristofoletti (Co-I) received a two-year FDA U01 award valued at $500,000. The development of generic Orally Inhaled Drug Products (OIDPs) currently requires considerable time and resources. This project leverages latest population pharmacokinetic (popPK) and physiologically based pharmacokinetic (PBPK) modeling and simulation approaches to evaluate, whether pharmacokinetic bioequivalence studies can reliably provide information on potential differences in the regional pulmonary drug deposition of orally inhaled drug products relevant for the bioequivalence assessment of generic OIDPs. Thereby, this project might result in a streamlined drug approval process for generic inhaled drug products.
Dr. Chengguo Xing with MPI Dr. Ramzi Salloum were awarded a three-year R33 titled, “The potential of kava in enabling tobacco cessation – its holistic effects in managing stress and insomnia associated with abstinence” totaling $1.5 million. This award aims to evaluate the effects of a specific dietary supplement (kava) on a panel of biological signatures associated with tobacco use, stress, and sleep via a double-blind randomized placebo-controlled three-arm clinical trial with the long-term goal of developing a kava-based tobacco cessation intervention.
Dr. Francine Azeredo and Drs. Stephan Schmidt were awarded $400,000 for four years from Gilead Sciences for a project titled “Development of a semi-mechanistic disease-drug platform for hepatitis B.” The partnership is to establish a disease-drug-trial platform for HBV by integrating viral dynamics markers and treatment effects. The final goal of the platform is to be used as a tool for testing/confirming hypothesis and decision-making during drug development.
Co-Investigator Awards
Drs. Haesuk Park and Jenny Lo Ciganic, in collaboration with Dr. Christopher Kaufmann, were awarded a grant from Sleep Research Society Foundation titled, “Longitudinal impact of narcolepsy and cardiovascular disease: A claims-based study” with $209,000 coming to the UF College of Pharmacy. This one-year study will seek to identify whether age at narcolepsy diagnosis and use of medications for narcolepsy (specifically stimulants) modifies associations between the disorder and both hard and subclinical cardiovascular disease outcomes and cardiovascular-specific health care resource utilization across the lifespan.
Drs. Stephan Schmidt and Almut Winterstein, in collaboration with Dr. Roger Fillingham in the UF College of Dentistry and Ohio State, were awarded funds from Agency for Healthcare Research and Quality R01. This project proposes longitudinal research among older adults to assess the associations of uncontrolled pain, co-occurring chronic conditions or geriatric symptoms (multimorbidity), and opioid–drug interactions with risk for opioid use disorder or overdose.
Drs. Chenglong Li and Robert Huigens are Co-Is on a five-year $2.5 million NICDR R01 with PI Dr. Jose Lemos in the UF College of Dentistry titled “Mechanisms of Metal Ion Homeostasis of Oral Streptococci.” The project aims to investigate the mechanisms utilized by S. mutans to survive under high zinc stress and determine how the use of zinc-containing dental hygiene products affects survival of bacteria associated with oral health or disease. Finally, they will explore the therapeutic potential of a S. mutans protein that confers zinc tolerance for the prevention and treatment of dental caries. Dr Li will be responsible for effort and management of ZccE structural modeling, inhibitor lead discovery and optimization through computer-aided structure-based design. Dr. Huigens will be responsible for overseeing the analogue design and chemical synthesis component of this award.
Dr. Julio Duarte, in collaboration with Dr. Ellen Keeley in cardiology, were awarded two years of funding from the American Heart Association totaling $200,000. The project “Omega-3 fatty acids and myocardial inflammation in HFpEF,” will measure heart muscle inflammation and the level of omega-3 fatty acids in patients with stiff heart muscles that cannot relax in an effort to prove that higher levels of omega-3 fatty acids will match up with less heart inflammation. If this is true, medicines that raise omega3 fatty acids may help patients with this type of heart failure.
Despite a grave unmet need, there exist no FDA-approved drugs for the treatment of psychostimulant use disorder. In this new UG3 (DA058553), Sparian Biosciences will develop drugs from the lab of Dr. Chris McCurdy acting as dual sigma receptor antagonists and inhibitors of the dopamine transporter. Drs. Jay McLaughlin, Abhisheak Sharma and Brandon Warren will examine the pharmacodynamic and pharmacokinetic properties of selected dual-acting ligands, collecting Pre-IND data to advance the lead molecule to Phase 1 clinical trials as a treatment for psychostimulant use disorder.
Graduate Student Awards
Hulin Tang was awarded a Pre-Doctoral Fellowship from AFPE totaling $10,000. The objective for the project, titled “Newer Glucose-Lowering Drugs and Risk of Parkinson’s Disease in people with type 2 diabetes.” The objective of this proposal is to compare the effectiveness and determine heterogeneous treatment effects (HTEs) of newer GLDs on the risk of PD among patients with T2D. The central hypothesis is that newer GLDs are associated with a lower risk of PD in older adults with T2D.
Francisco Marchi through Dr. Jatinder Lamba’s R01 titled “Genomics of AML Prognosis” was awarded a diversity supplement. The supplement proposes to leverage artificial intelligence and machine learning tools to develop DNA methylation-based signatures of clinical utility in pediatric AML. Of note, all the DNA methylation data to be used in this proposal is already available and was generated in part during previous cycle of the parent R01. The long-term goal is to develop a robust a DNA methylation signature with high sensitivity and specificity that can be rapidly translated to clinics for patient prognostication.
Nam Nguyen was awarded a Pre-Doctoral Fellowship from AFPE totaling 10k. The objective for the project, titled “CRISPR Synthetic Lethality Screen Identifies Genomic Resistant/Sensitive Modulators of Standard Chemotherapy in Pediatric Acute Myeloid Leukemia (pAML),” is to perform a custom genetic loss-of-function synthetic lethal CRISPR screen to elucidate the molecular determinants underlying the sensitivity and resistance to standard chemotherapies and other approved treatments, as well as to profile novel biomarkers, targets and pathways for drug resistance. Custom functional screens driven by selected genes will reduce false discovery due to robust statistical power and further characterize drug sensitive/resistant functional modulators in depth compared to our previous laborious and expensive genome-wide loss of-function screens. The long-term goal is to apply these findings to personalize and prioritize treatment to improve patient outcomes.