Cancer

Many organic small molecules serve as drug leads for drug discovery and drug development programs. Understanding the structure and mechanism of action of these small molecules is essential for drug lead optimization. Also having a reliable synthetic access to these organic small molecules is important to aid in SAR studies and lead optimization in the search for new drugs for various diseases. Dr. Adu-Ampratwum's area of interest includes exploring novel synthetic methods for the synthesis of small organic molecules as lead compounds for drug discovery. His current research area focuses on designing and synthesizing small molecules to study HIV and cancer biology and as potential therapeutics.

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.

Dr. Carcache de Blanco's research interests focus on the discovery of bioactive constituents from natural product sources with potential application in cancer chemoprevention and chemotherapy. She is also interested in the study of botanical dietary supplements and other herbal products used in traditional medicine.

Dr. Cheng’s laboratory aims to develop an interdisciplinary research program centered on Computer Aided Drug Design and Discovery. Closely collaborating with experimental chemists and biologists, our group utilizes a myriad of computational modeling & simulation, and data analytics techniques to understand molecular basis of drug action and to rationally design new drug molecules. Our group also has long-standing interests in: a) developing and applying multiscale computational techniques to investigate the structure, dynamics and function of complex biomolecular (and cellular ) systems; and b) bridge large-scale molecular simulation with systems biology (cellular metabolism and signaling networks) towards a new drug discovery paradigm.

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.

The research in Dr. Fuchs' lab focuses on the design and preparation of bioactive 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 and modification of lead compounds, and the optimization of drug properties. The overarching goals of these studies are to understand the mechanisms through which small molecules interact with proteins or other biomolecules in the context of disease progression and to improve the potential utility of promising new compounds to help them advance toward the clinic. Recently, the Fuchs lab has collaborated with numerous labs in the areas of natural product drug development for various cancers, the preparation of protein degraders active against leukemia, and HIV-1 capsid and integrase drug development.

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

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.

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 research interests of Dr. Kinghorn are on the isolation, characterization and biological evaluation of natural products of higher plant origin, and he has worked in particular on compounds with potential antimicrobial, cancer chemotherapeutic, cancer chemopreventive, sweet-tasting, and bitterness-blocking effects, in addition to the scientific study of botanical dietary supplements.

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. Lee's lab is focused on targeted drug delivery systems based on nanoparticles. Nanoparticles can serve as carriers of therapeutic agents, including nucleic acids such as siRNA, miRNA and anti-miRs, and facilitate their therapeutic delivery. The lab's effort is focused on improving nanoparticle composition based on rational design and directed at clinical applications. Ongoing projects include developing miR-targeting lipid nanoparticles and targeted chemotherapeutic drug formulations and bioconjugates for therapy of solid tumors, leukemias, diabetic wounds, and other diseases.

Dr. Li’s research interest focuses on the design, syntheses and studies of small molecules for cancers and infectious diseases. In the cancer area, our group focus on prostate and pancreatic cancer. Novel molecules are developed using the strategies of drug repurposing and structure-based drug design (in collaboration with Dr. Xiaolin Cheng). In the research of infectious disease, our focus is on the development of small molecules for the treatment of COVID-19. Novel molecules are generated through computational chemistry, molecular modeling and virtual screening targeting the interface of spike protein and human ACE-2 receptor.

Dr. Peterson’s research group works to design, synthesize, and discover small molecules that affect the proliferation of cancer cells and associated immune cells that support malignancy. To identify these compounds, the Peterson laboratory synthesizes fluorescent molecular probes as tools for drug discovery. These probes are used to create target-based or phenotypic drug discovery assays to identify anticancer agents with novel mechanisms of action. To optimize and evaluate these compounds, they use synthetic organic chemistry, medicinal chemistry, and chemical biology approaches. In conjunction with high throughput screening by confocal microscopy, flow cytometry, and other related techniques, his laboratory identifies chemical probes of biological systems, uncovers mechanisms of biologically active agents, and discovers hit and lead compounds for the development of therapeutics.

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).

New natural product sources (new and unidentified fungal and bacterial microorganisms, microbial endophytes, new endemic and medicinal plant species, etc.) contain many undiscovered potential bioactive secondary metabolites that can be used to combat world’s deadly diseases including cancer, malaria, viral infections, and chemoresistance. Their investigation must be prioritized in order to discover new pharmacophores for potential drug candidates. My lab focuses on (1) bioassay-guided isolation, structural elucidation and development of bioactive compounds from natural sources, (2) Drug discovery from Madagascan natural products and (3) drug discovery from ethnomedicine. One of our recent ongoing projects is on the development of insecticides that can be used to control mosquito vector of Zika virus from Madagascan endemic plants.

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. 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).