Facilities & Labs
Members of the Garrett lab met with breast cancer advocate Patty Emery in March 2019. From left: graduate student Samar Alanazi, Rosalin Mishra, PhD, Joan Garrett PhD, Patty Emery, graduate students Long Yuan and Hima Patel
The overarching aim of our research program is to better understand signal transduction pathways involved in cancer. Our work covers the gamut of basic cancer biology through translational studies in mouse models and human tissues, and interfaces with clinical trials. Our lab uses a variety of technologies including mammalian tissue culture, molecular analyses of gene and protein expression, gene expression microarrays, next-generation DNA sequencing, bioinformatics, protein microarrays, mass spectrometry, mouse models, and live animal imaging.
Experimental Therapeutics
We are interested in developing new strategies to combat cancer, particularly cancer metastases and drug resistance. The motivation stems from the recognition that metastatic cancer represents a devastating eventuality affecting cancer patients with high relapse and mortality rates for which there are currently no effective therapies. Chemotherapy, radiation and surgery are the mainstays of cancer treatment. We adopt the best elements of these modalities into building a treatment design that has the systemic reach of chemotherapy and the spatiotemporal control of radiotherapy and surgery. We accomplish this by selecting light-sensitive chemotherapeutics and activating them with photoelectronic energy from radiopharmaceuticals to impart precision in cell killing akin to molecular surgery (Nature Nanotech, 2015; Nature Commun, 2018).
Experimental Imaging
We are also interested in developing new strategies to precisely image infectious agents in the body in real-time using clinical imaging modalities. The motivation stems from the recognition that there are no contrast agents in clinical use that can identify the different pathogens accurately, swiftly and in real-time. We are designing probes that would have high selectivity for the pathogen and avoid uptake by mammalian cells to provide superior contrast during imaging. We employ the entire process workflow, including cell based assays and animal models, to evaluate the probes for clinical applications as well as investigational tools to better understand host-pathogen and pathogen-pathogen interactions.
Welcome to the Experimental Molecular Imaging and Therapeutics (EMIT) Lab. We are an interdisciplinary research group with interests in design and development of new investigational and interventional tools for human diseases, from cancer to infections. We combine the principles of pharmacology, chemical biology, nanoscience, molecular biology, nuclear imaging and microbiology to find exciting ways to solve biomedical challenges.
Experimental Therapeutics
We are interested in developing new strategies to combat cancer, particularly cancer metastases and drug resistance. The motivation stems from the recognition that metastatic cancer represents a devastating eventuality affecting cancer patients with high relapse and mortality rates for which there are currently no effective therapies. Chemotherapy, radiation and surgery are the mainstays of cancer treatment. We adopt the best elements of these modalities into building a treatment design that has the systemic reach of chemotherapy and the spatiotemporal control of radiotherapy and surgery. We accomplish this by selecting light-sensitive chemotherapeutics and activating them with photoelectronic energy from radiopharmaceuticals to impart precision in cell killing akin to molecular surgery (Nature Nanotech, 2015; Nature Commun, 2018).
Experimental Imaging
We are also interested in developing new strategies to precisely image infectious agents in the body in real-time using clinical imaging modalities. The motivation stems from the recognition that there are no contrast agents in clinical use that can identify the different pathogens accurately, swiftly and in real-time. We are designing probes that would have high selectivity for the pathogen and avoid uptake by mammalian cells to provide superior contrast during imaging. We employ the entire process workflow, including cell based assays and animal models, to evaluate the probes for clinical applications as well as investigational tools to better understand host-pathogen and pathogen-pathogen interactions.
Our research specialty is in the area of complex fluids, nanotechnology, microfluidics, neutron scattering and drug delivery. We combine experimental and theoretical approaches to develop novel nano-architectures with applications in the areas of sustainability, green chemistry, pharmaceuticals/drug encapsulation and delivery, surfactant and formulation science, gas sorption and material science.
Supramolecular Chemistry
Our research focuses on synthesizing novel cavitands, and their complexes with metal, photoactives, and drugs. Preorganization of cavitands in a bowl shape with upper- and lower-rim functionality, offers a favorable environment for guest interaction and inclusion. In particular, we are interested in rationalizing the principles of self-assembly, templation and nucleation, through combined solid and solution phase studies.
Complex Fluids
The mobility and involvement of solvent molecules are different in crystals and in gels. We are particularly interested in studying the nucleation and equilibriums involved in the following hierarchical assembly processes:
- One-dimensional growth of gel fiber
- Crystallization of nano-assemblies in space (three-dimensional growth)
- Binary nucleation process in a supramolecular gel phase crystallization (multi-dimensional grwoth)
Neutron Scattering
We utilize small angle neutron scattering (SANS) technique to study the size and shape of self assembled systems (colloid, microemulsion, fibrillar assembly, metal nanocapsule, polymer), in solution.
Also, we use neutron reflectometry technique to estimate the penetration of an active in free state and in complexed (to our synthesized host) state into a model skin membrane.
Crystal Engineering
In our group, we exploit the principles of Crystal Engineering to design new functional materials. In particular, we are interested in the encapsulation of photoactives and active ingredient compounds by non-covalent molecular assemblies. This includes capture of substrates in molecular nanocapsules or nanotubules assembled by means of hydrogen bonding or non-covalent interactions.
Soft Multiporous Framework
We aim to exploit macrocycle-derived supramolecular gel network as an inexpensive, synthetically tuneable and efficient, multiporous system for selective gas sorption and separation.
Cosmetic Science
To develop cosmetics that are safe and effective on human skin, manufacturers must have a deep understanding and knowledge of the chemistry involved in the formulations and their mechanisms of action. Our research focuses on integrating principles of modern biophysics into materials that would define the next generation of this field. We assess structure-property relationships to develop novel skin care, oral care and hair care products. In addition, we probe into mechanisms of delivery and deposition actives onto the skin/hair and elucidate the parameters to control them. We construct novel nanometric delivery vehicles, based on the principles of self-assembly and molecular recognition.
Dr. Georg F. Weber has made major contributions to metastasis research by discovering the interaction between the molecules osteopontin and CD44, by defining the physiologic role of metastasis genes as stress response genes, and by identifying a gene expression core signature of metastases. While his laboratory continues to address fundamental questions, other ongoing research seeks new venues for diagnosis and therapy of cancer progression.
Anti-Cancer Metastasis Treatment
We had earlier shown that cancer dissemination is controlled by aberrant expression or splicing of metastasis genes. We recently found that metastatic gene expression patterns are generally characterized by a core program of gene expression that induces the oxidative metabolism, activates vascularization/tissue remodeling, silences extracellular matrix interactions, and alters ion homeostasis. This program distinguishes metastases from their originating primary tumors as well as from their target host tissues. (Hartung et al. A core program of gene expression characterizes cancer metastases. Oncotarget 2017;8:102161. Hartung et al. Site-specific gene expression signatures of cancer metastases. Clin Exp Metastasis, DOI 10.1007/s10585-019-09995-w 2019). We are exploring ways to target the core signature with suitable drug combinations.
Nuclear Osteopontin
The cytokine Osteopontin is an important progression mediator in over 30 cancers. This lab has contributed some of the most significant advances to understanding the underlying mechanisms. We have reported the importance and uniqueness of Osteopontin splicing in cancer. Several Osteopontin variants are expressed in invasive, but not in non-invasive, human tumor cells. These splice variants may be indicators for progression or recurrence risk and for treatment responses (He et al. An osteopontin splice variant induces anchorage independence in human breast cancer. Oncogene 2006;25:2192. Zduniak et al. Osteopontin variants in breast cancer treatment responses. BMC Cancer 2016;16:441.Walaszek et al. Breast cancer risk in premalignant lesions: Osteopontin splice variants indicate prognosis. Brit J Cancer 2018;119:1259). In some cancer cells, spliced osteopontin is present in the nucleus. We are studying the role of nuclear osteopontin in cancer progression.
Mitochondrial Effects by Osteopontin
Cancer metabolism has experienced a renaissance of research interest since 2006. We were among the first groups to report that cancer cell metabolism during metastasis is dramatically different from the much-studied Warburg effect. Enhanced energy production is a prerequisite in this process. Osteopontin-c supports anchorage-independence through inducing oxidoreductase genes that are associated with the mitochondrial energy metabolism and with the hexose monophosphate shunt. The Osteopontin-a-induced glucose uptake fuels this process. (Shi et al. Osteopontin-a alters glucose homeostasis in anchorage independent breast cancer cells. Cancer Lett 2014; 344:47. Shi et al. Energy metabolism during anchorage independence. Induction by osteopontin-c. PlosOne 2014;9:e105675. Weber. Metabolism in cancer metastasis. Int J Cancer 2016;138:2061). The impact of Osteopontin on mitochondrial function is incompletely elucidated. We are working on deepening our understanding of it.