My work focusses on the use of cell line expression data and corresponding drug responsiveness with the goal of identifying predictive expression profiles that will better direct use of effective therapeutics and avoid ineffective options.
Medications with high anticholinergic activity have adverse effects on neuropsychological performance. We are quantifying neuropsychological performance relationships with anticholinergic burden and genetic factors in patients with psychotic disorders, first degree relatives, and controls. We ultimately aim to identify key genetic variants associated with anticholinergic effects on cognitive phenotypes.
Using pre-clinical modeling to identify transcriptomic signatures that accurately predict drug resistance in multiple myeloma. Additionally, we are testing new chemotherapeutic approaches to target unique features of the myeloma epigenome and improve the efficacy of current therapies.
I am a senior undergraduate student in the College of Biological Sciences at the University of Minnesota. My research project involves studying Multiple Myeloma and the long-term effects of an epigenetic modifying drug called EPZ-6438 on human myeloma cell lines. This drug is an EZH2 inhibitor; EZH2 is a protein complex in the cell attributed with oncogenic activity in Multiple Myeloma. Thus far we have concluded EPZ-6438 to be a potential novel therapy in treating Multiple Myeloma.
Pharmacogenomic determinants of the serum uric acid lowering effects of the drug fenofibrate. We aim to determine if there are genetic markers that can be used as predictors of both drug response and serum uric acid levels that can be used to help guide clinical decision making in order to improve treatment of gout and help ease the burden of comorbid cardiovascular disease.
The current lifetime prevalence of psychotic disorders is approximately 4.1% with non-response to standard treatments being in the range of 40-50%. This reveals a need for improvements in current treatment practices and the use of pharmacogenomics can help to improve the precision of individual patient treatments; therefore, we are aiming to analyze various dopamine receptor and transporter single nucleotide polymorphisms (SNPs) in relation to participant’s antipsychotic dosing.
Fludarabine and cyclophosphamide are chemotherapeutics used in hematopoietic cell transplant (HCT) preparative regimens for their anticancer and immunosuppressive properties. We are investigating the relationship between fludarabine and cyclophosphamide pharmacokinetics, single nucleotide polymorphisms (SNPs), and non-relapse mortality, neutrophil engraftment, overall survival and acute graft-versus-host disease in patients undergoing allogeneic nonmyeloablative HCT. Understanding the relationships between target SNPs, pharmacokinetics, and clinical outcomes will facilitate the development of a personalized approach to HCT preparative regimens that improves safety and overall survival while minimizing the risk of acute graft-versus-host disease.
Tacrolimus is the cornerstone immunosuppressive agent after kidney transplantation, but its high pharmacokinetic variability is a well-known problem which contributes to adverse effects and poor outcomes. We are investigating the associations between intra-patient tacrolimus pharmacokinetic variability, CYP3A5 loss of function alleles, and acute rejection in a large cohort of African American and European American kidney transplant recipients.
MicroRNAs regulate gene expression, participate in normal neuro developmental and physiological processes, and have recently been implicated in the pathogenesis of several psychiatric disorders. My project aims to examine the relationship between microRNA genetic variants and antipsychotic treatment response outcomes in patients with psychosis. We hope that this project will enhance our understanding of miRNAs as therapeutic biomarkers in psychiatric disorders.
Methylphenidate is the most commonly prescribed medication to treat ADHD and it is metabolized to its inactive form by the CES1 protein. We are looking for variants within the CES1 gene that may explain differences in clinical response, side effect profile and dosing requirements in pediatric patients with ADHD.
Past Pharmacogenomic Trainees
Malek Okour, PhD
Pharmacokinetics and pharmacodynamics analysis of mycophenolic acid (MPA) in kidney transplant recipients. We aim into individualizing therapy while keeping in mind exposure relation to acute rejection and side effects.
Rebecca Pulk, PharmD
Tacrolimus is a calcineurin inhibitor immunosuppressant that widely used in kidney transplant. I am working to improve our ability to select an optimized tacrolimus dose for kidney transplant patients based on their individual clinical and genetic factors to decrease time to optimal coverage and improve clinical outcomes.
Youssef Roman, PharmD, PhD
The contribution of genetic polymorphisms in select genes responsible for uric acid disposition and the drugs used to treat hyperuricemia and gout. My ultimate goal is to identify key genetic variants to be used for guided drug selection to optimally manage patients with gout, hyperuricemia, and their associated comorbidities.
Kinjal Sanghavi, PhD
Improving immunosuppressive therapy in transplantation using population pharmacokinetic and pharmacogenetic approach. These approaches were used to optimize dosing for tacrolimus (for kidney transplant recipients) and fludarabine (for hematopoietic stem cell transplant recipients).