Pharmaceutics & Pharmacology

Dr. Baker’s cancer-relevant research interests broadly cover translational and clinical pharmacology of anti-cancer agents. Recently, her laboratory has focused on the preclinical development of anti-cancer agents for the treatment of acute myeloid leukemia (AML), with an emphasis on tyrosine kinase inhibitor (TKI) drug combinations. Dr. Baker’s research interests include developmental therapeutics for AML, clinical pharmacology of tyrosine kinase inhibitors, variability in anti-cancer drug disposition and investigational anti-cancer drug development.

My research is focused on cardiac arrhythmias (abnormal heart rhythms), particularly in heart failure. We use an integrated approach from proteins to cells to tissues to the intact organism to study the causes, and potential treatments of cardiac arrhythmias. My clinical practice is at the Ambulatory Care Center at the Ross Heart Hospital, where I provide patient care in antiarrhythmic medication monitoring.

Dr. Cocucci studies basic mechanisms of membrane trafficking and is interested in how these processes deviate during cancer development when compared to normal cells. His research adopts multiple techniques, including traditional biochemistry, cell biology, and high resolution fluorescent live cell microscopy. Dr. Cocucci’s goal is to define novel targets for cancer therapy and to improve drug delivery, studying the internalization pathways and the mechanisms of endosomal escape adopted by artificial and biological nanovectors.

Dr. Coss' research focuses on endocrine disease mechanisms and developing novel therapies for advanced prostate cancer. He also has an interest in chemoprevention of prostate and hepatocellular carcinomas using novel hormonal approaches.

My current research focuses on determining how targeted and cytotoxic chemotherapy impact the brain and how drug transporters contribute to these effects. Consistent with this research, I am interested in the translational pharmacology of anticancer therapeutics, especially the characterization of preclinical and clinical pharmacokinetics and pharmacodynamics.

Dr. Govindarajan’s laboratory is interested in understanding and overcoming drug resistance in pancreatic cancer. His training is in the areas of animal sciences, cancer biology and drug transport-based pharmacokinetics, and has extensively used cell and animal models to evaluate nucleoside and oligonucleotide therapies. He also developed several new insights into the pharmacology and cytotoxicity of nucleoside analog drugs. Current focuses in his laboratory are to understand the epigenetic alterations in pancreatic cancer and to evaluate novel epigenetic reversal agents for effective pancreatic cancer treatment. Understanding epigenetic regulation of pluripotent stem cell factors in microRNA biogenesis is also of interest.

Dr. Guo works on both basic research and its subsequent practical applications, focusing on understanding the mechanisms and assembly of viral DNA packaging motor, and using components of the biomotor for various applications. By applying interdisciplinary approaches including chemistry, biophysics, biochemistry, nanotechnology, bioengineering, molecular biology, cell biology, computer modeling, and pharmaceutical sciences, Dr. Guo studies RNA, DNA and proteins and their interaction.

Dr. Guo’s current project areas are:

RNA nanotechnology and its application for the delivery of siRNA/miRNA/drug for the treatment of cancers, viral infection, and genetic diseases
Nanobiotechnology, including structure, function and mechanism of Phi29 DNA-packaging nanomotor
Single molecule imaging and optical instrumentation to study the interaction of RNA, DNA, and protein
Single pore technology for DNA sequencing, macromolecule detection, and disease diagnosis, using channels of variety of viral DNA packaging motors

Our research team members are engaged in pre-clinical target identification for pharmacologic treatment of neurodegenerative and psychiatric disorders. We use in vivo and in vitro high-resolution fluorescence microscopy and high-content analysis of live neurons to reveal complex interactions between signaling pathways that regulate cell survival/function and circadian clock signaling. This work is designed to identify new avenues of chronotherapeutic target development for CNS disorders. Current work focuses on two related themes: (1) Alzheimer’s Disease and desynchronization of cortico-limbic circadian rhythms and (2) MAPK signaling: gates, oscillators and circadian timing.

The overall goal of Dr. Hu’s research is to evaluate the contribution of uptake transporters, in particular OCT and the OATP1B-type transporters, in the disposition and toxicity of anticancer drugs, with particular emphasis on peripheral neurotoxicity. Her laboratory utilizes multi-level approaches including in vitro, in vivo models, aims to understand the underlying mechanisms that drive the extensive inter-individual pharmacokinetic variability, drug transporter regulation, antitumor efficacy, and drug-drug interaction in response to drug therapy in cancer patients. Another area of research interest is to design of preclinical and clinical studies to evaluate pharmaceutical agents as modulators of side effects associated with tubulin poisons, such as paclitaxel and vincristine.

The long-term research goal in Dr. Hu's laboratory is to understand the mechanisms in myocardial ischemia and cardioprotection. The lab is particularly interested in studying the regulation of ion channels and their signaling molecules in the cardiovascular system, with a special emphasis on subcellular localization, traffic regulation, molecular mechanisms and their physiological relevance, particularly as these processes relate to human cardiovascular diseases. The ultimate goal is to explore the challenges in identifying therapeutic targets and to help developing preventive and therapeutic strategies for cardiovascular diseases.

The Hoo (Hu) research group focuses on the functional and mechanistic exploration of immune cell-derived extracellular vesicles (EVs) and EV-DNA in the context of diseases such as cancer and chronic inflammatory disorders. The ultimate goal is to inform the rationale design of non-viral gene therapies and diagnostic/prognostic tools. Specific research interests include functional and mechanistic exploration of immune cell-derived EVs and EV-DNA in disease settings such as cancer and auto-immune disorders, engineering core-shell lipid nanoparticles (LNPs) for the targeted delivery of nucleic acids, proteins, peptides, and small molecules to support therapeutic development for cancer, chronic inflammatory diseases, and autoimmune disorder and diagnostic/prognostic biomarker development based on circulating EVs and EV-DNA.

Dr. Johnson’s research is focused on understanding genetic and other sources of variability in drug response, building evidence to support translation of research to clinical practice, implementing genomic medicine in practice and documenting clinical outcomes associated with use of genomic medicine in practice. Her discovery research focuses primarily on cardiovascular drugs used in the treatment of hypertension and heart failure and used to prevent blood clots. Her pharmacogenetics implementation work is across a range of therapeutic areas and explores clinical trial approaches for documenting its impact on clinical outcomes. She’s also deeply committed to training the next generation of clinical and translational scientists.

Dr. Kebriaei’s research is focused on treatment of multi-drug resistant bacterial infections. Some examples of the diseases associated with these infections include bacteremia, endocarditis, bone and joint infections and implant associated infections.

Her current work is concentrated on both planktonic and biofilm states of bacteria and novel approaches for combating multi-drug resistant infections. She utilizes various classes of antimicrobials with distinct mechanisms of action to discover optimal treatment options for a wide range of infectious diseases. In addition, she designs and operates pharmacokinetic/pharmacodynamic models to simulate humanized doses in vitro. The majority of knowledge achieved from this research is translatable to bedside and leads to better patient outcomes.

The overarching goal of the Kroetz laboratory is to understand the molecular basis of interindividual variability in drug response and toxicity. Genomic association studies are used to identify genes and pathways involved in common toxicities associated with cancer therapy, including taxane-induced peripheral neuropathy and bevacizumab-induced hypertension. Functional genomic studies are then used to define the role of these genes and pathways in the dose-limiting toxicities. A second area of research is on the role of ABC transporters in drug resistance and physiologic function. Ongoing efforts include cryo-EM studies of MRP4 and investigation of MRP4 in resistance to immunotherapy.

Dr. Phelps’ lab is involved in both pre-clinical and clinical development of numerous small molecule anti-cancer and immuno-modulatory agents under development. Their work aims to understand the mechanisms involved in the absorption, distribution, metabolism, and excretion (i.e. pharmacokinetics, PK) of these agents, and how both the PK and pharmacodynamic (PD) effects of these agents are altered by genetic differences (polymorphisms) among individuals (i.e. pharmacogenetics, PG).

Professor Jennifer (Jen) Plahovinsak is the Director of the Master of Science in Translational Pharmacology program. Jen’ s research focuses on the design and development of technology-enhanced learning environments for science education, graphic and instructional design to support learning, key learner characteristics for graduate students, curricular development for online toxicology courses, and quality strategies for online program success. Additionally, her interests include the development of relevant preclinical models to support medical countermeasure research programs. Jen has been certified as a Diplomate of the American Board of Toxicology since 2015.

Research in the Radwański lab focuses on cardiac biophysics and pharmacology with the twin goals of understanding the mechanisms of life-threatening abnormal heart beats (cardiac arrhythmias), and developing effective antiarrhythmic therapies. By leveraging experience as both a clinical pharmacist and a cardiovascular researcher, and using cutting-edge biophysical approaches ranging from the single-ion channel level to the whole organism, they have identified a novel arrhythmia mechanism. Neuronal-type sodium channels account for a tiny fraction of sodium channels in the heart, but exert a disproportionately strong influence on cardiac calcium dynamics, particularly in disease. By applying pharmacology principles, in the context of this fundamental insight, they are developing novel therapeutic approaches, which effectively prevent arrhythmias, while avoiding the lethal side effects usually associated with classical antiarrhythmic agents. In essence, Dr. Radwański’s approach could be summarized as better clinical outcomes through basic scientific insights.

Dr. Sparreboom's research studies the contribution of solute carriers to chemotherapy-induced toxicity profiles, identifies chemical inhibitors of critical transporters, translates the findings to clinical trials in collaboration with scientists and oncologists, and ultimately improves the long-term outcome of patients with cancer by modulating the therapeutic window of widely-used chemotherapeutics. His research is currently focused on the development of transport modulators that could be used in conjunction with platinum-based drugs and tyrosine-kinase inhibitors, with emphasis on the development of innovative preclinical model systems.

Dr. Wei's area of research expertise is in geriatric pharmacoepidemiology, with specific focus areas on drug safety, drug effectiveness, and quality of medication prescribing in older adults, especially those with pain, neurodegenerative diseases (e.g., Alzheimer’s disease and related dementia [ADRD]), and nursing home stays.

Dr. Yalowich’s lab focuses on mechanisms of action and resistance to a class of anticancer agents known as DNA topoisomerase IIα (TOP2α; 170 kDa ) inhibitors, such as the anticancer agent etoposide. Ongoing projects characterize alternative RNA processing/intronic polyadenylation of TOP2α pre-mRNA that results in formation of a 90 kDa truncated form of TOP2α in acquired resistance to etoposide. Strategies to circumvent drug resistance involve CRISPR/Cas9 gene editing to restore proper RNA splicing function in resistant cells. In addition, the role of micro-RNAs as determinants of anticancer drug resistance is under investigation. Finally, the Yalowich lab actively collaborates with Dr. Mark-Mitton-Fry from the Division of Medicinal Chemistry and Pharmacognosy to evaluate the mechanisms of action and efficacy of newly synthesized Novel Bacterial Topoisomerase Inhibitors (NBTIs).