Sharyn Baker, PharmD, PhD
The research in Dr. Baker’s lab is focused on identifying mechanisms of drug resistance in Acute Myeloid Leukemia and the preclinical evaluation of new therapeutic strategies to treat or circumvent resistance. These studies utilize molecular biology, pharmacology and next generation sequencing techniques and in vitro/in vivo models of cancer. Her research also involves characterizing the clinical pharmacology of investigational and approved anticancer agents in laboratory models and cancer patients to improve drug therapy. Dr. Baker’s lab works in a collaborative team environment so that the most promising preclinical findings are translated to clinical trials, and in turn, clinical observations provide feedback to inform preclinical studies.
Moray Campbell, PhD
Dr. Campbell’s research goals include understanding how epigenetic disruption of transcriptional programs drive hormone-responsive cancers, such as prostate and breast cancer, and exploiting this understanding in diagnostic and therapeutic settings. Specifically, he has focused on distortion of the actions of nuclear hormone receptors in these cancers, via several mechanisms including altered functions of co-regulators, such as NCOR2/SMRT, and disrupted targeting by non-coding RNA, such as miRNA. Within the context of prostate cancer, Dr. Campbell has extended this work to examine epigenetic mechanisms that contribute to cancer health disparities. To achieve these goals, his research focuses on the analyses and integration of high-dimensional datasets to dissect genomic and epigenomic mechanisms.
Xiaolin Cheng, PhD
Dr. Cheng’s research centers on computational drug discovery and design. His research utilizes a myriad of molecular modeling and simulation techniques (e.g., molecular dynamics, free energy calculations, etc.) and data analytics (e.g., machine learning, network analysis, etc.), to understand the molecular basis of drug action and to design rationally small-molecule therapeutics. Working at the interface between medicinal chemistry and structural pharmacology, Dr. Cheng’s goal is to bring a dynamics and systems perspective into the structure-based drug design paradigm. In this context, his laboratory is particularly interested in the design and discovery of allosteric and multi-target drugs for the treatment of cancer and other diseases.
Ema Cocucci, MD, PhD
Dr. Cocucci studies basic mechanism 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.
Christopher Coss, PhD
Roughly half of all cancer patients experience unexpected weight loss as a consequence of their disease. This phenomenon is known as cancer cachexia and is associated with reduced quality of life, increased risk of adverse response to cancer treatment and overall increases in cancer-related death. Despite being recognized for millennia, cancer cachexia has no known effective treatment. Dr. Coss’ Lab focuses on therapeutically targetable cachectic mechanisms. The drivers of cachexia are not well understood and an improved understanding of anabolic resistance and catabolic processes in cachectic animal tissues inform his team's novel therapeutic approaches for the treatment of cancer cachexia. His lab also focuses on chemotherapeutic drug disposition in cachectic cancer patients. Incredible heterogeneity exists between cancer patients’ body composition and how drugs behave once administered. An improved understanding of how patient body composition impacts chemotherapeutic drug disposition will inform the design of improved chemotherapeutic dosing regimens.
Yizhou Dong, PhD
Dr. Dong’s research, cell-specific and multifunctional drug delivery in vivo, has been regarded as one of the most challenging issues in the field of drug delivery. A wide variety of cell types in humans still cannot be efficiently and specifically reached by delivery systems such as lung epithelial cells, metastatic tumor cells, and immune cells. An even more formidable task is delivering multiple payloads into specific cells and tissues. In order to address these challenges, Dr. Dong’s Drug Discovery and Delivery Laboratory focuses on the following research areas, developing cell specific drug delivery systems, constructing multifunctional drug delivery systems and demonstrating therapeutic efficacy of these systems in animal models for treating genetic disorders, infectious diseases and cancers.
Platform biotechnologies under development in the Drug Discovery and Delivery Laboratory include:
- Developing new biomaterials for therapeutic and diagnostic applications
- Engineering RNA molecules including mRNAs and the CRISPR systems
- Constructing targeted drug conjugates such as antibody/ligand drug conjugates.
James Fuchs, PhD
The research in Dr. Fuchs' lab designs and prepares novel molecules for therapeutic applications against cancer and infectious diseases. His lab utilizes fundamental chemical knowledge and synthetic methodology to facilitate the process of drug discovery and development through the generation of biological probe molecules, the synthesis of lead compounds and the optimization of drug properties.
Rajgopal Govindarajan, DVM, PhD
The Govindarajan lab is interested in understanding the solute carrier (SLC) transporters in health, disease, and drug disposition. The focus of research has been on the generation and characterization of null-mutant (knockout) mice carrying targeted disruptions of mouse SLC genes. The scope of work encompasses research related to the development of targeted therapies for SLC-mutated human genetic disorders and experimental therapies for human pancreatic cancers.
Dale Hoyt, PhD
The circulatory system delivers blood to all parts of the body, and is compromised by many diseases such as atherosclerosis, stroke and heart attacks. Blood vessels may also grow into cancerous tumors and help them to expand and metastasize. By discovering drugs that can help or hurt blood vessels, they may be able protect the circulatory system and normal organs or inhibit cancer growth. Dr. Hoyt’s lab focuses on how stresses, including DNA damage, bacterial infection and inflammation can be manipulated to help or hurt blood vessel cells. His lab is assessing new drug targets in vascular cells to accomplish this.
Shuiying Hu, PhD
Many chemotherapeutic agents can cause neurological side effects, impacting quality of life. The incidence of chemotherapy-induced peripheral neuropathy (CIPN) is particularly high with agents such as paclitaxel and oxaliplatin, occurring in up to 80% of patients receiving such agents. There are currently no effective strategies for prevention of CIPN, and rationally designed intervention studies are needed to better address this gap. Dr. Hu’s research interests are focused on the development of transport modulators that could be used in conjunction with neurotoxic chemotherapy to understand drug transporter regulation mechanism; to determine the role of drug transporters on anticancer agents induced inter-individual pharmacokinetic variability, antitumor efficacy and drug to drug interaction; to evaluate contribution of solute carrier to chemotherapy-induced CIPN; and to develop preclinical and clinical studies with potential implications to ameliorate the incidence and severity of debilitating side effects of cancer drugs.
A. Douglas Kinghorn, PhD, DSc
The research in Dr. A. Douglas Kinghorn’s lab deals with the extraction, purification, and characterization of the chemical structures of biologically active substances of tropical plants. Examples of the use to society of these lead compounds are as potential cancer chemotherapeutic and chemopreventive agents, therapies for the tropical infectious disease leishmaniasis, and as sweetening and taste-modifying components of foods and beverages.
Robert J. Lee, PhD
Dr. Lee’s lab is working on developing nanoparticle-based drug delivery systems. Many cancer drugs have side effects and can be made safer and more efficacious with novel drug delivery systems. Other drugs such as oligonucleotides require an effective delivery system to be translated into the clinic. Dr. Lee’s lab is focused on developing lipid-based and targeted drug delivery systems for drugs and nucleic acids with potential applications in oncology and other diseases.
Tom Li, PhD
Dr. Li‘s lab focuses on the design, synthesis and biochemical testing of small molecules for cancer and infectious diseases. For the cancer area, his lab focuses on prostate cancer, the second most common cancer in the U.S. Androgen deprivation therapy (ADT) has been the mainstay of prostate cancer therapy. However, most patients will progress to castrate resistance prostate cancer (CRPC) after several years of treatment. The survival rate of CRPC is only 30%. Dr Li’s research effort focuses on the design of several classes of agents to treat CRPC. In the area of infectious disease, his lab focuses on the design of agents for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection, which causes 20,000 U.S. deaths per year. The agents his lab is designing target metabolic pathways unique to bacteria. In both the prostate cancer and MRSA areas, they have generated several series of compounds and are currently undertaking active testing.
Navjot Pabla, PhD
Dr. Pabla's laboratory studies the pathological signaling mechanisms that contribute to the development and progression of renal disorders. Acute kidney injury and renal cell carcinoma are the two major areas of interest. They utilize high-throughput screening assays and functional genomics to identify molecular targets for renal diseases, followed by validation in mouse models of kidney diseases. The overall goal of these studies is to identify new therapeutic strategies to treat acute kidney injury and renal cell carcinoma, diseases for which no effective therapies are currently available.
Blake R. Peterson, PhD
Dr. Peterson’s research group is working to discover small molecules that affect the proliferation of cancer cells and associated immune cells that support malignancy. To find these compounds, the Peterson laboratory creates fluorescent molecular probes that are designed to facilitate drug discovery. These probes are used in conjunction with phenotypic drug discovery methods to identify both anticancer agents with novel mechanisms of action and their molecular targets. To optimize and evaluate these compounds, they use synthetic organic chemistry, medicinal chemistry, and chemical biology approaches. These strategies, in conjunction with assays based on confocal microscopy, flow cytometry, and other fluorescence-based techniques, provide a platform for the identification of new therapeutic agents.
Mitch A. Phelps, PhD
Dr. Phelps’ research aims to develop novel anticancer and immune-modulatory therapies and improve upon existing therapies through translational research. This includes clinical research studies that aim to evaluate the clinical pharmacology of novel or existing, FDA-approved therapies, or their combinations, in patients with various forms of hematologic and solid tumor malignancies. Dr. Phelps’ group uses quantitative bioanalysis and pharmacometric approaches (PK/PD modeling and simulation) to explore mechanisms of drug resistance, identify individual patient factors contributing to PK and PD variability, and individualize dosing regimens. Pharmacometric and quantitative approaches are also applied in preclinical in vitro and in vivo animal models to study effects observed in the clinic and to support development of novel, targeted agents (small molecules, oligonucleotides, and proteins) and/or novel drug delivery platforms (immunoliposomes, exosomes).
Alex Sparreboom, PhD
The Sparreboom lab is interested in mechanisms by which small-molecule anticancer drugs reach sites of elimination and indirectly affect inter-individual pharmacokinetic variability. Ongoing projects are focused on the role of the transporters OCT2 and MATE1 in the pharmacokinetics of platinum-based chemotherapeutics, and utilize an arrays of experimental models, including transporter-deficient zebrafish, mice, and rats. Within the Experimental Cancer Pharmacology Laboratory, members of the Sparreboom lab actively collaborate with Dr. Sharyn Baker on characterizing the pharmacokinetic properties of novel agents used in the treatment of acute myeloid leukemia, and with Dr. Shuiying Hu on the contribution of organic anion transporting polypeptides to the toxicity of tubulin poisons.
Jack Yalowich, PhD
Dr. Yalowich’s lab focuses on the mechanisms of action and resistance to a class of anticancer agents known as DNA topoisomerase II (topo IIα) inhibitors, such as the anticancer agent etoposide; a natural product analog. Ongoing projects characterize alternative RNA processing of topo IIα pre-mRNA that results in decreased expression of topo IIα 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. A variety of natural products are also under study as new and effective anticancer agents. Finally, members of the Yalowich lab actively collaborate with Dr. Mark-Mitton-Fry to evaluate the mechanisms of action and efficacy of newly synthesized Novel Bacterial Topoisomerase Inhibitors (NBTIs).