The Pharmacometrics Center of Excellence (PCE) partners strong faculty knowledge base in computer modeling of drug efficacy and toxicity with wet-lab analytic approaches. Together, the group is highly expert conducting pre-clinical through post-marketing studies. The Center builds on the existing synergies in the University's Core Facilities.

Mission

To DESIGN innovative strategies that maximize safe and effective pharmacotherapy, to DEVELOP the next generation of translational clinicians and scientists through advanced pharmacometric education, and to DISSEMINATE the results to improve health outcomes.

Investigators

Director: Marc Scheetz, Pharm.D., MSc
Dr. Scheetz is a Professor and Director of the 1) Midwestern University Pharmacometrics Center of Excellence, and 2) Post-Doctoral Fellowship Program in Infectious Diseases Pharmacotherapy. He currently practices as an Infectious Diseases pharmacist at Northwestern Memorial Hospital in downtown Chicago. Dr. Scheetz's primary research interest lies in the interface of the pharmacokinetic/pharmacodynamic interaction (i.e. between antimicrobials, pathogens, and hosts).He is particularly interested in assessing modifiable pharmacologic variables in the treatment of infectious diseases and identifying optimal exposures against the backdrop of toxicity.His group studies toxicology in the laboratory, as well as through clinical data modeling. Dr. Scheetz is actively engaged in drug development and formerly served as a member of the FDA Antimicrobial Drugs Advisory Committee.

N. "Jim" Rhodes, Pharm.D., MSc
Dr. Rhodes is an Associate Professor and member of the Midwestern University Pharmacometrics Center of Excellence. He currently practices as an Infectious Diseases and Antimicrobial Stewardship pharmacist at Northwestern Memorial Hospital in downtown Chicago. Dr. Rhodes's interests include anti-infective pharmacokinetics and pharmacodynamics. His research is primarily focused on clarifying the antimicrobial-exposure-response profiles in pre-clinical and translational models. His research program also seeks to evaluate how contemporary antimicrobial utilization influences resistance and clinical outcomes. He is actively engaged in infectious diseases organizations and serves as a reviewer for multiple peer-reviewed journals and funding organizations.

Medha Joshi, MPharm, Ph.D.
Dr. Medha D. Joshi is an Associate Professor in Pharmaceutical Sciences at Midwestern University's College of Pharmacy, Glendale Campus. Dr. Joshi has expertise in lipid based drug delivery systems including solid lipid nanoparticles (SLN), micro emulsions, self-emulsifying drug delivery systems (SMEDDs), nanosuspensions, and liposomes etc. targeted drug delivery. Her research program at Midwestern university is focused on application of nanoparticulate targeted delivery a) to neurogenetic peptides for their delivery to the blood brain barrier, and b) reduction of maternal-fetal toxicity of drugs across the placental barrier. She has more than 30 peer-reviewed research articles, two patents, and three book chapters to her credit. She has been a principle investigator and co-investigator on several intramural and extramural grants, including the Alzheimer's Drug Discovery Foundation and NIH AREA grants.

Annette Gilchrist, Ph.D.
Dr. Annette Gilchrist is an Associate Professor with Midwestern University, and adjunct faculty member at Northwestern University. Dr. Gilchrist has a PhD in Immunology from the University of Connecticut Health Center and a MS in Biochemistry from the University of Connecticut. Previously, she was with Cue Biotech and Caden Biosciences, companies she co-founded that focused on identifying modulators of G protein-coupled receptors (GPCRs) utilizing novel approaches (US Patent Numbers 6,559,128; 7,208,279; and 7,294,472). Her current research is on allosteric and functionally selective modulators of GPCRs with her primary receptors of interest being the chemokine receptor CCR1 and the recently deorphanized FFAR2. Dr. Gilchrist is an International Editor for the British Journal of Clinical Pharmacology and recently served as a guest co-editor for a Frontiers in Endocrinology Bone Research themed issue on "Chemokines and Bone."

Shridhar Andurkar, Ph.D.
Dr. Andurkar serves as Professor and Chair of the Department of Pharmaceutical Sciences. He earned his M.S. and Ph.D. in Medicinal Chemistry from Auburn University, Department of Pharmaceutical Sciences. He completed his postdoctoral studies at the University of Houston, Department of Chemistry. Dr. Andurkar has more than 25 years of experience in the design, synthesis, isolation and purification, structural elucidation, drug metabolism, and pharmacological studies of bioactive molecules. His current research interests are in the design, synthesis, and pharmacological evaluation of novel analgesics and antiepileptic agents, as well as the study of novel synthetic organic chemical methodologies, stereoselective synthesis, and evaluating the impact of stereochemistry on biological activity. He serves as scientific advisor to Aagami Inc., and Pharmazz Inc.

Gwendolyn Pais, Ph.D.
Dr. Gwendolyn Pais is a Scientist within the Midwestern University Pharmacometrics Center of Excellence. Dr. Pais earned her PhD from the University of Illinois at Chicago for her research on the mechanism of estrogen regulation of Notch in breast cancer. She completed a Postdoctoral training in Molecular Pharmacology at Midwestern University with the Gulati group where she worked on endothelin-1 as a potential biomarker of renal injury in neonates of different gestational ages. She is currently engaged in identifying biomarkers of renal injury in preclinical studies with the Scheetz group to aid in the Pharmacokinetic/Toxicodynamic (PK/TD) modeling of antibiotics in infectious diseases. Her interests include utilizing quantitative systems pharmacology to prevent drug-induced nephro and neurotoxicity.

Roxane Rohani, Pharm.D.
Dr. Roxane Rohani is currently a fellow in the Infectious Diseases Pharmacotherapy Fellowship program at Midwestern University's College of Pharmacy. As a part of the fellowship, Dr. Rohani is clinically engaged at Northwestern Memorial Hospital with a focus in Infectious Diseases and Antimicrobial Stewardship. Dr. Rohani’s ongoing research involves pharmacokinetic-pharmacodynamic modeling and simulation of antimicrobials to optimize their clinical use and safety. 

Jack Chang, Pharm.D.
Dr. Jack Chang is a fellow in the Infectious Diseases Pharmacotherapy Fellowship program at Midwestern University’s College of Pharmacy. As a part of the fellowship program, Dr. Chang also practices as an infectious diseases pharmacist at Northwestern Memorial Hospital in downtown Chicago. Dr. Chang was engaged in antimicrobial stewardship and quality improvement metrics during his PGY1 residency. His research interests are focused on developing pharmacokinetic, pharmacodynamic, and toxicodynamic models in order to achieve translational advances in antimicrobial utilization and safety.  

Student Involvement

We welcome interested students to join in our research. Current CPDG students may access our opportunities via the “CPDG Resources” Canvas site, then click “Faculty Research Participation,” then click the link found under “Connect with Faculty,” and review our investigators’ options that are listed.

Publications & Presentations

Publications:
Miglis C, Rhodes NJ, Liu J, Gener J, Hang E, Scheetz M. Quantifying the Importance of Active Antimicrobial Therapy among Patients with Gram-negative Bloodstream Infections: Cefepime as a Representative Agent. International Journal of Antimicrobial Agents. 2018. Epub 2018/10/14. doi: 10.1016/j.ijantimicag.2018.10.004. PubMed PMID: 30315921.

Avedissian SN, Scheetz MH, Zembower TR, Silkaitis C, Maxwell R, Jenkins C, Postelnick MJ, Sutton SH, Rhodes NJ. Measuring the impact of varying denominator definitions on standardized antibiotic consumption rates: implications for antimicrobial stewardship programmes. Journal of Antimicrobial Chemotherapy. 2018;73(10):2876-82. Epub 2018/08/08. doi: 10.1093/jac/dky275. PubMed PMID: 30085084.

Presentations:

Joshi M, Chang J., Hlukhenka K., Pais G., Avedissian S., Gulati A., Prozialeck W, Hubka T., Scheetz MH, Griffin B. (2018) Elucidation of fetal and maternal vancomycin-induced kidney injury using a pregnant rat model, PharmSci 360, November 2018, Washington DC.

Joshi M, Hlukhenka K., Pais G., Prozialeck W, Scheetz M, Griffin B. In vitro evaluation of vancomycin loaded liposomes for its potential of reduced nephrotoxicity in rat epithelial kidney (NRK) cells, ASHP Midyear 2018

Aljefri D, Avedissian S, Rhodes NJ, Postelnick M, Scheetz MH. 1391. Vancomycin Area under the Curve (AUC) to Predict Nephrotoxicity: A systematic Review and Meta-analysis of observational studies. ID Week; San Francisco 2018.

Avedissian S, Liu J, O'Donnell J, Pais G, Becher L, Joshi M, Prozialeck W, Lamar P, Lodise TP, Scheetz MH. 1419. 24-Hour Pharmacokinetic Relationships for Intravenous Vancomycin and Novel Urinary Biomarkers of Acute Kidney Injury. ID Week; San Francisco 2018.

Avedissian S, Rhodes NJ, Liu J, Aljefri D, Postelnick M, Sutton S, Zembower T, Martin D, Pais G, Cruce C, Scheetz MH. 1821. Understanding the components and calculation of the SAAR, Illustrative Data. ID Week; San Francisco 2018.

Cruce C, Postelnick M, Martin D, Sutton S, Wunderink R, Zembower T, Scheetz MH, Rhodes NJ. 209. Impact of a risk-based CAP prescribing guideline paired with antimicrobial stewardship to improve antibiotic prescribing for patients at low risk for drug resistant pathogens. ID Week; San Francisco 2018.

Lee B, Constantino-Corpuz J, Apolinario K, Wang S, Nadler B, Scheetz MH, Rhodes NJ. 1068. Evaluation of Cefazolin versus Anti-Staphylococcal Penicillins for the Treatment of Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections in Acutely-Ill Adult Patients: Results of a Systematic Review and Meta-Analysis. ID Week; San Francisco 2018.

Liu J, Avedissian S, Pais G, Joshi M, Rhodes NJ, Scheetz MH. 1394. A Translational Pharmacokinetic Rat Model of Cerebral Spinal Fluid (CSF) and Plasma Concentrations of Cefepime. ID Week; San Francisco 2018.

Liu J, Mercuro N, Davis S, Yarnold P, Patel T, Petty L, Kaye K, Scheetz MH. 1871. Identifying time periods of high and low vancomycin use. ID Week; San Francisco 2018.

Facilities

Laboratory:
Facilities for laboratory work to be performed in Science Hall and Alumni Hall on the Downers Grove Campus of Midwestern University (MWU) is detailed below. Science Hall is a state-of-the-art research building that opened in 2011. This five-story 209,149 sq. ft. scientific research facility is located in the center of MWU's 125-acre campus. Dr. Scheetz has a lab in Science Hall (i.e. room 547A, across the hall from his dedicated laboratory space in the Animal Facility). Dr. Scheetz's primary laboratory in Science Hall is sufficient for all work described here (~750 sq. ft. shared with 250 sq. of dedicated space for Dr. Scheetz). Well-functioning equipment include: -80⁰ C freezer (TSU Series, Thermo Scientific), -20⁰ C freezer (VWR), a 4⁰ C refrigerator (VWR), X-600M notifiable temperature monitoring system with probes for all freezers and refrigerators (Xytronix), CO2 incubator (Eppendorf Galaxy® 170 S), Oven (Isotemp 500 series, Fisher Scientific), Biological Safety Cabinet Class II Type A2 (LabGard ES, NuAire), Refrigerated Centrifuge (Thermo Sorvall 4L), Metabolic Shaking Incubator (Dubnoff), Fixed speed vortex mixer (VWR), Bacti-Cinerator IV (Mc Cormick Scientific), DEN-1 McFarland Densitometer (Grant-bio), programmable micro-infusion Pump (kd Scientific), three Fusion Touch Pumps (SAI Infusion Technologies), inverted tissue culture microscope (Nikon Eclipse TS2), inverted fluorescence microscope (Nikon Eclipse TiE), microtome (Microm), cryostat (Microm HM 505 E), blade sharpener (Leica SP9000), weighing balance (Ohaus PA 124C, 120 g max weighing capacity). Two modern computers exist for student and personnel use in the laboratory, including necessary software and a laser printer (See Technology) within the SH547A laboratory. LN2 storage dewars exist for storage of cell lines in Science Hall 307, a shared space for investigators.

Xenobiotic assay work is completed in a newly opened CORE laboratory, which is within a 5-minute walk of the Center investigators. The College of Pharmacy purchased an Agilent 1260 Infinity Binary LC paired with Agilent 6420 Triple Quadrupole LC/MS system (2017). A service contract exists on the LC-MS/MS and associated software through 2022. As a backup, a HPLC is available in an assay laboratory. Well-functioning equipment in the assay lab include: HPLC (Agilent Technologies, 1260 Infinity with Thermostat, Quaternary Pump, assay software, and computer), weighing balance (Ohaus PA 84C, 80 g max weighing capacity), refrigerated centrifuge (Sorvall ST 40R, Thermo Scientific), UL Transonic Cleaner (FS 110, Fisher Scientific), refrigerator with -20⁰C freezer (Fisher Scientific), and microwave oven. Redundancy in instruments protects against down-time for repairs.

Midwestern University Core Facility:
Our projects are supported by the instruments and technical staff in the Midwestern University Core Facility. This 1,360 ft2 facility located on the Downers Grove campus is fully supported by Midwestern University and houses state-of the-art instruments that are available to faculty, staff, and students. Instrument training and maintenance is overseen by a dedicated research associate and elected faculty advisor. The shared instruments that will be used include Beckman Coulter CytoFLEX flow cytometer with 488nm and 638nm lasers, Sakura Tissue-Tek VIP tissue processor and Tissue-Tek TEC embedding station, Thermo Scientific MICROM HM 325 microtome, Jeol JCM-6000 Plus Scanning Electron Microscope with tilt and rotating stage, Leica EM ACE600 sputter and carbon coating system, Eppendorf 5920R refrigerated centrifuge, Agilent 6420 Triple Quad LCMS, Perkin Elmer EnSpire Plate Reader with absorbance, luminescence, fluorescence, and time resolved fluorescence. Additional CORE equipment available for use include the MAGPIX xPONENT 4.1 System with MILLIPLEX Analyst Single Seat, Enspire Multimode Plate reader (Perkin Elmer) and the Applied Biosystems 7300 Real Time PCR System thermocycler. The MAGPIX xPONENT system allows the multiplexing of the biomarker proteins. The Applied Biosystems 7300 Real Time PCR System thermocycler is housed in the core facility room SH405. The confocal microscope (Nikon A1A) is core equipment located in Science Hall 429.

All laboratory space, personal and shared, is easily accessible to investigators and can be accessed within a 5 minute walk from their offices. The Center members are experts in the use of the equipment detailed here.

Computer/Technology:
MWU Information Technology Services (ITS) maintains all of the computers and printers, and supports software applications. Statistical data modeling is completed with the following software programs that have been purchased or have been freely obtained with a perpetual license by Center members: Stata Statistics/Data Analysis v15.0, SigmaPlot 13.0, R version 3.5.1 with Pmetrics v.1.5.2 library, GraphPad Prism v7.04, TableCurve 2D v.5.01, SPSS v.19 with add-on module SPSS Classification Trees 13.0, ADAPT Pharmacokinetic/Pharmacodynamic Systems Analysis Software 5.0.49 utilizing Compaq Visual Fortran v6.6 Standard-Academic, GFortran, and USC*PACK. All PC-based computers have a wide spectrum of institutionally-licensed Microsoft Office Software. All MWU computers are wired to the University's local area network which provides reliable, fast access to the Internet. ITS provides excellent technical support.

Contact Us

Feel free to reach us at MWUPCE@midwestern.edu