Daniel Gonzalez Lab
Daniel Gonzalez Lab
I am an Associate Professor in the Division of Pharmacotherapy and Experimental Therapeutics (DPET) at the UNC Eshelman School of Pharmacy. DPET seeks to improve lives by leading the world in translating experimental and clinical pharmacology discoveries into precision medicine.
The primary goal of my research program is to optimize pharmacotherapeutic efficacy and safety through the use of innovative clinical trial designs and application of mathematical modeling and simulation techniques, with an emphasis in pediatric populations. This is first accomplished by characterizing the differences in pharmacokinetic (PK) and pharmacodynamic (PD) relationships across human development, elucidating and quantifying influential factors of drug disposition, and the degree of interindividual variability surrounding them. Assessment of such changes are then related to deviations in drug effects and overall patient outcomes. With such characterizations established, optimal dosing regimens are derived, with a clinical impact in patient populations for which evidence-based dosing recommendations are frequently absent.
My experiences have afforded a highly collaborative and multidisciplinary research program that leverages pharmacological, mathematical, and statistical concepts for better-informed clinical trial design and medical decision-making. My research group is involved in numerous drug development programs focused on evaluating pediatric use of both new and off-patent therapeutics. As a principal investigator, I have received funding from the National Institutes of Health as well as the Thrasher Research Fund, have authored over 70 manuscripts and abstracts to advance such practice, and have served as the primary research advisor for 7 post-doctoral fellows and 3 graduate students.
Clinical Pharmacology Studies in Children
Quantification of pharmacokinetic (PK) and pharmacodynamic (PD) parameters and the factors that influence them constitute the major focus of my research program. The unique constellation of ethical and logistical considerations inherent to pediatric drug trials present immense challenges in accruing sufficient data through traditional approaches. Children thus represent a vulnerable and understudied patient population, resulting in widespread off-label use of medications.
By performing clinical pharmacology studies and employing both population and physiologically-based PK/PD modeling and simulation techniques, we seek to characterize differences in drug exposure and effect across the pediatric age spectrum and identify the clinical correlates most associated with favorable pharmacotherapeutic outcome. The ultimate goal of such an approach is the provision of pediatric dosing information to clinicians for the betterment of patient care.
My group is directly involved in drug development programs focused on characterizing PK/PD properties, safety, and efficacy of new and off-patent drugs in the pediatric population.
Use of Electronic Medical Record Data to Assess Drug Disposition, Efficacy, and Safety
There are often ethical and logistical challenges to performing clinical trials in the pediatric population. Electronic medical record (EMR) data represents an easily accessible and voluminous resource for the assessment of drug efficacy and safety outcomes. In addition, for drugs where drug concentrations are assessed as part of routine medical care, these data can be used to validate existing PK/PD models. My group is involved in multiple projects focused on characterizing the clinical pharmacology properties of drugs widely used in the pediatric population using EMR data.
Daniel Gonzalez, Pharm.D., Ph.D.
Daniel Gonzalez’s research interests include pediatric clinical pharmacology and the application of mathematical modeling and simulation techniques to characterize the pharmacokinetics and pharmacodynamics of drugs, guide dosage selection, and improve drug safety in children.
Jaydeep Sinha, Ph.D.
Dr. Jaydeep Sinha is a pharmacist and a pharmacometrician by training. Dr. Sinha is an Assistant Professor in the Department of Pediatrics of the UNC School of Medicine and an affiliate of the Gonzalez Lab. His current research focuses on delivering safe and effective drugs to children using clinical pharmacology modeling and simulation (M&S). Dr. Sinha earned his Ph.D. degree in pharmacometrics from the University of Otago in New Zealand. He worked in M&S roles for several years in academia and the pharmaceutical industry, including his experience as a postdoctoral research associate at the UNC Eshelman School of Pharmacy and as a translational M&S scientist at a Bristol Myers Squibb drug discovery research center.
Victória Etges Helfer is a UNC/GSK PK/PD Fellow. She received her Ph.D. in Pharmaceutical Sciences at the Federal University of Rio Grande do Sul, Brazil. Her research and training were focused on the application of popPK modeling approach to evaluate antimicrobial brain penetration and its effect against resistant bacteria. Currently, her research interests include the development and application of population PK/PD and PBPK models to optimize drug use in special populations.
Angela Jeong, Pharm.D., Ph.D.
Angela Jeong is a UNC/Nuventra PK/PD Fellow. Prior to joining the fellowship, Angela received her PharmD and PhD in Experimental and Clinical Pharmacology at University of Minnesota. During her PhD training, Angela studied the role of a post-translational protein lipidation called prenylation in the pathogenesis of Alzheimer’s using immunoassays, transcriptome, and click chemistry-meidated metabolic labeling of prenylation substrates. Her current research project in Gonzalez lab involves the application of PBPK modeling of PPI in children with obesity. Angela is also interested in developing a quantitative systems pharmacology model for pathology progression in neurodegenerative disorders including Alzheimer’s disease.
Patty Maglalang is a graduate student in the Division of Pharmacotherapy and Experimental Therapeutics. Patty obtained her Doctor of Pharmacy degree in 2021 at the University of Minnesota. During her undergraduate and pharmacy training, she conducted translational and clinical research such as preclinical studies and pharmacokinetic modeling to investigate novel therapeutics for rare neurological disorders. Her research interests include utilizing clinical pharmacology tools to optimize the efficacy and safety of therapeutics in the fields of neurology and special populations.
Sean McCann is a graduate student in the Division of Pharmacotherapy and Experimental Therapeutics. He received his Bachelor of Science in 2018 from Kettering University in Michigan. Previously, he conducted preclinical research focusing on toxicology, oncology, and pharmacokinetics in both industry and academic institutions. His research includes pharmacokinetic/pharmacodynamic modeling of off-patent drugs in pediatric populations.
Liz Thompson is a graduate student in the Division of Pharmacotherapy and Experimental Therapeutics and a Pediatric Cardiology and Critical Care fellow at Duke University. She is currently also a Duke Clinical Research Institute Research Fellow and part of the collaborative UNC-Duke Clinical Pharmacology T32 Training Program. She obtained her MD from Georgetown University School of Medicine. Her research interests include characterizing and optimizing drug use in critically ill children with congenital heart disease using modeling and simulation.
Wendy Wen obtained her Bachelor of Science in Pharmaceutical Sciences degree in April 2020 and Doctor of Pharmacy degree in April 2022 at the University of Pittsburgh School of Pharmacy. During her undergraduate training, she conducted meta-analysis in evaluating alarm criteria for interpreting the significance and diagnostic value of somatosensory evoked potential in spine surgery and conducted research in characterizing connections between human aquaporin 2 and Nephrogenic Diabetes Insipidus. During her Pharm.D. training, she conducted pre-clinical research in development and evaluation of 20-hydroxyeicosatetraenoic acid (20-HETE) CYP inhibitors to ameliorate brain injury after pediatric cardiac arrest. She also conducted clinical research in the development of a robust UPLC-MS/MS method for the simultaneous quantification of sildenafil and N-desmethyl sildenafil in multiple biological matrices. Her research interests include using pharmacokinetic/pharmacodynamic modeling tools and clinical pharmacology tools to optimize drug therapies and evaluating safety and efficacy of therapeutics in pediatric populations.
|Jackie Gerhart||2017-2022||Ph.D., M.B.A.||Associate Director, Pfizer, Collegeville, PA|
|Stephen Balevic||2019-2022||M.D., Ph.D., M.H.S.||Assistant Professor of Adult and Pediatric Rheumatology, Duke University, Durham, NC|
|Sara Salerno||2015-2020||Pharm.D., Ph.D.||Senior Quantitative Pharmacologist, Gilead Sciences, Inc.|
|Christoph Hornik||2015-2019||M.D., Ph.D., M.P.H.||Associate Professor of Pediatrics, Duke University, Durham, NC|
Academic Post-Doctoral Fellows
|Jennifer Ford||2020-2021||Ph.D||Scientist, Johnson & Johnson, Spring House, PA|
|Jaydeep Sinha||2019-2021||Ph.D.||Assistant Professor, UNC School of Medicine, Chapel Hill, NC|
|Samit Ganguly||2018-2020||Ph.D.||Scientist, Clinical Pharmacology at Regeneron Pharmaceuticals, Tarrytown, NY|
|Shufan Ge||2017-2018||Ph.D.||Manager, Modeling & Simulation, Pharmacokinetics, Pharmacodynamics, and Metabolism at Sanofi, Bridgewater, NJ|
Dr. Alan Forrest
|2015-2017||Pharm.D.||Associate Director, Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT|
|Nilay Thakkar||2015-2016||Ph.D.||Clinical Pharmacologist, Clinical Pharmacology & Modeling and Simulation at GlaxoSmithKline, Philadelphia, PA|
UNC/GSK Pharmacokinetics/ Pharmacodynamics Post-Doctoral Fellows
|Eleni Caratzas||2020-2022||Ph.D., MSc.||Senior Scientist, Clinical Pharmacology and Pharmacometrics, Janssen Pharmaceuticals, Spring House, PA|
|Fernando Carreño||2019-2021||Ph.D.||Manager, Clinical Pharmacology Modeling and Simulation, GlaxoSmithKline, Collegeville, PA|
UNC/IQVIA Pharmacokinetics/ Pharmacodynamics Post-Doctoral Fellows
Dr. Kim Brouwer
|2014-2015||Ph.D.||Director of Clinical Pharmacology, EMD Serono, Billerica, MA|
|Michael Hwang||2016-2017||Pharm.D.||Clinical Pharmacokineticist, MedImmune, San Francisco, CA|
Dr. Julie Dumond
|2017-2018||Pharm.D.||Principal Scientist, Novartis, Boston, MA|
UNC/Nuventra Pharmacokinetics/ Pharmacodynamics Post-Doctoral Fellows
|Shirley Wu||2018-2019||Pharm.D.||Pharmacometrician, Nuventra, Durham, NC|
UNC-Duke Collaborative Clinical Pharmacology T32 Post-Doctoral Fellows
|Ryan Beechinor||2016-2018||Pharm.D.||Clinical Oncology Pharmacist, Department of Pharmacy, University of California, Davis Medical Center|