Dr. Caritis and Dr. Venkataramanan have worked collaboratively over the past 30 years in the field of Obstetric Pharmacology. A large group of research scientists at the University of Pittsburgh serve as co-investigators for the OPRC and provide mentoring to trainees in their specific areas of expertise. Drs. Venkataramanan and Caritis have been awarded the only T-32 training grant in Obstetric Pharmacology in the United States [LINK TO PROGRAM]. T32 trainees are integrated into the Pittsburgh OPRC.
Steve Caritis, MD, is a specialist in Maternal-Fetal Medicine with considerable experience in pharmacology, clinical trials, collaborative research and federal and industry-supported research in pharmacology. In addition to being the PI for the OPRU for the last 11 years, Dr. Caritis was the PI for the Maternal-Fetal Medicine Units Network for 25 years where he directed three pharmacologic intervention trials and several pharmacokinetic and pharmacodynamics studies. Drs. Caritis and Venkataramanan have reported on the pharmacology of 17-hydroxyprogesterone caproate (17-OHPC) and have suggested that the currently recommended dose may be inadequate for a significant proportion of treated women. The pharmacokinetic properties of and fetal exposure to 17-OHPC were described in singleton gestation as part of an OPRU-funded multicenter trial. Dr. Caritis has suggested a new strategy for administration of glyburide based on data from an OPRU–funded study. Drs. Caritis and Venkataramanan have reported that the dose of oseltamivir may need to be increased by 40% in pregnant women to provide the same exposure seen in non-pregnant subjects. Dr. Caritis and Venkataramanan have performed a pharmacokinetic and pharmacodynamic study with ProStrakan, a pharmaceutical company, to evaluate the pharmacokinetics of the granisetron patch (Sancuso) when used for nausea and vomiting of pregnancy. Dr. Caritis participated in a clinical trial by Duchesne that recruited pregnant women with nausea and vomiting of pregnancy. The results of this trial led to approval of Diclectin for the disorder. Dr. Caritis’ role as educator in the field of Obstetric Pharmacology is demonstrated in the awarding of the T-32 and his many teaching and mentoring roles. Dr. Caritis supervises research staff in all aspects of subject recruitment, writing of progress reports, submission of abstracts and manuscripts related to the clinical projects, submission of proposals to the IRB, and he provides clinical teaching and supervision of trainees in the clinical arena.
Raman Venkataramanan, PhD, is a basic, translational, and clinical investigator in this project. He is Professor of Pharmaceutical Sciences at the University of Pittsburgh School of Pharmacy. He also holds a joint appointment as Professor of Pathology in the University of Pittsburgh School of Medicine. He is a member of the Magee-Womens Research Institute (MWRI), Thomas E. Starzl Transplantation Institute, and the Center for Clinical Pharmacology and the McGowen Institute for Regenerative Medicine at the University of Pittsburgh. He is the Director of the Clinical Pharmacokinetics Laboratory at the University of Pittsburgh and the Therapeutic Drug Monitoring Program at UPMC. Dr. Venkataramanan is an expert in the field of biopharmaceutics and pharmacokinetics. The primary goal of Dr. Venkataramanan’s research is to identify factors that regulate the pharmacokinetics and pharmacodynamics of drugs in various patient populations in order to optimize drug therapy. In collaboration with the PI, Dr Steve Caritis, he has studied the pharmacokinetics of several drugs (ritodrine, 17-OHPC, oseltamivir, granisetron). In addition to the clinical studies, he also uses in vitro systems (human hepatocyte cultures, microsomes, isolated organ perfusion systems) and animal models to mechanistically understand the regulation of various processes that alter drug absorption and disposition. His group has developed analytical methods for measuring 17-OHPC, characterized the stability, metabolic fate and drug interactions of 17-OHPC, and has evaluated the effect of pregnancy on various CYPs, UGTs and transporters using primary cultures of human hepatocyte cultures. In these ongoing studies, he is evaluating the mRNA expression, protein expression and activity of several drug metabolizing enzymes and transporters and the pharmacokinetics of several drugs. Dr. Venkataramanan has mentored 36 graduate students, more than 60 undergraduate students and 23 fellows and several junior faculties. He also has been recognized for his mentoring activities by the University of Pittsburgh (Mentoring Award – 2009), by the American College of Clinical Pharmacology (BMS Mentor Award-2009) and by the American Pharmacists Association (Tyler Ward for stimulation of clinical research – 2010. Dr. Venkataramanan will oversee all laboratory related activities, provide input for the clinical pharmacology work, analyze pharmacokinetic and pharmacodynamics data, and will supervise staff and trainees in the laboratory.
Co-Investigators in the Pittsburgh OPRC
Phil Empey, PharmD, PhD, has successfully conducted clinical studies that prospectively isolated RNA from normal and lactating breast tissue samples for microarray expression profiling of drug transporters during lactation. Through this work he identified the active transport processes that were up regulated in humans during breastfeeding and that may be responsible for the accumulation of medications in breast milk. He has also developed a breast cancer resistance protein overexpressing cell line in order to conduct flux assays for screening drug interactions with this transporter, which is highly expressed during lactation.
Xiaochao Ma, PhD, has worked in the field of pharmacology and toxicology for 16 years with a focus on drug-drug interactions and drug toxicity. His laboratory has considerable experience in studying human pregnane X receptor (PXR) and its role in regulation of drug metabolism and toxicity. He utilizes genetically engineered mouse models in his research. In addition, he is interested in identifying small molecule biomarkers of drug-induced liver injury using a metabolomic approach.
Thomas Nolin, PharmD, PhD, is focused on mechanistically examining the effect of kidney disease and renal replacement therapy on pharmacokinetics, pharmacodynamics, non-renal drug clearance, and elucidating the impact of altered non-renal clearance on corresponding drug exposure and response. He has also overseen the development, validation, and implementation of numerous analytical methods, including a novel ultra-high performance liquid chromatography-tandem mass spectrometry method for measuring multiple analytes simultaneously.
Jane Pringle, PhD, is an epidemiologist by training with extensive experience in health services research. Her particular areas of expertise are addiction services research, especially research involving the application of screening, brief intervention and referral to treatment (SBIRT) within various healthcare settings. She has conducted numerous health services research studies and program evaluation efforts involving innovative addiction treatment, intervention and prevention models. She is the Co-Chair of the Pennsylvania Department of Drug and Alcohol Program’s Clinical Standards Committee, and is a consultant to the Substance Abuse Mental Health Services Administration (SAMHSA) in their review of state behavior health homes.
Lisa Rohan, PhD, has focused on design of drug delivery strategies and development of biologically relevant in vitro models for vaginal microbicides formulation assessment. Her laboratory has experience with the development of pharmaceutical products utilizing many dosage form platforms including ring, semi solids including hydrogels and polymeric dosage forms. She has developed delivery systems for small molecule, protein and peptide, and genetically modified bacteria anti-HIV drug candidates.
Greg Siegle, PhD, is an Associate Professor of Psychology with expertise in the use and integration of psychophysiological data including pupillometry and sympathetic measures such as galvanic skin response with clinical data. Dr. Siegle directs the Program in Cognitive Affective Neuroscience (PICAN) at the Western Psychiatric Institute. His expertise will assist in evaluating biomarkers of withdrawal.
Alex Soto, MD, PhD, is interested in developing organotypic cultures with multi-cellular cues for complete and stable maturation of stem-derived liver cells to engineer functional human liver tissue in vitro and use them for modeling liver drug discovery and therapeutics. He has focused on hepatic development and the molecular pathways of mouse and human embryonic stem cell differentiation towards mature hepatic phenotype. He has designed a simple and effective differentiation protocol involving natural stages of liver development by the addition of soluble factors and the co-culture of a combination of non-parenchymal liver cell lines for improved maturation and developed novel biological and surgical approaches in hepatic cell therapies.
Ralph Tarter, PhD, is a specialist in drug addiction research, who has been funded by NIDA and has directed the University of Pittsburgh Center for Education and Drug Abuse Research (CEDAR) over the last 20 years.
Jon F. Watchko, MD, is a Neonatologist at Magee who has participated in care of infants in the NICU over the last 25 years. Dr. Watchko has published extensively on p-glycoprotein and helped write the clinical care guidelines at Magee for drug addicted newborns.
Alan Wells, MD, MSc, has been investigating tumor progression (focusing mainly on the hormone-responsive breast and prostate carcinomas) since 1994. His work is focused on the whole of tumor progression including metastatic competency and phenotypic plasticity. Working with Dr. Linda Griffith (MIT) using her liver organotypic bioreactor, he has evaluated the functional capacity of hepatcoytes in 3-D microfluidic architecture.
Sean Xie, PhD, MBA, is the Director of the Computational Chemical genomics screening center (funded recently by NIDA). The goal is to develop novel computational chemical genomics, computational biology and computational genomics technologies for facilitating quantitative systems pharmacology and translational research in the area of drug abuse/addiction and neurological disorders. He has published many computational chemistry algorithms and cheminformatics tools, including LiCABEDS (Machine learning algorithm based novel GPCR ligand affinity and specificity prediction), CLAP (3D chemistry-space matrix based compound library acquisition profiling algorithm), FastMolPol (fast approaches for molecular polarizability calculations), ga-QSAR (genetic algorithm-optimized QSPR models for bioavailability, protein binding, and urinary excretion), LigFrag-RPM (Residue Preference Mapping of PDB Ligand Fragments), Fragment-based QSAR algorithm, HTDocking, TargetHunter, and BBB-predictor.
Wen Xie, MD, PhD, has a broad background in the functional characterization of nuclear hormone receptors and sulfotransferases, with specific training and expertise in key research areas for this application. He has laid the groundwork for the research by dissecting the roles of nuclear receptors and their target drug metabolizing enzymes in physiology and diseases.