The context of molecular and cellular function in normal and diseased states is altered due to changes in the tissue microenvironment. Cellular function studied independently of the primary microenvironment may incompletely report molecular events critical to disease progression. Mentors within this team examine complex microenvironment as a component of the disease process. Their specific foci include host-microbe interaction in the context of tissue-specific inflammation; novel imaging technologies to probe disease progression in intact organisms; and stromal and epithelial cell interactions, crosstalk mechanisms, reconstitution of physiologically optimal microenvironment composition and organization, and accurate cellular retention of primary phenotypic responses in vitro. This team has internal synergy and adds novel mechanistic strength to the other teams.
Associate Professor of Biological Sciences
Research focus: Host immune response to viral infections. School of Biological Sciences.
- State University of New York at Geneseo, Geneseo, New York - B. S. in Biology, 1987
- University of Rochester, School of Medicine and Dentistry, Rochester, NY - M. S. in Microbiology and Immunology, 1994 Ph.D. in Microbiology and Immunology, 2002
Host responses to viral infection involve both innate and adaptive immunity. Dr. Brown's laboratory investigates how the activation of pattern recognition receptors in innate immunity impacts the development of T cell responses to infection, specifically focusing on CD4 T cell activation and the mechanisms by which they mediate protection against acute or chronic infection. Her current work uses pattern recognition receptor agonists as a vaccine strategy to enhance memory T cell responses and provide protection against lethal influenza infection. Students in Dr. Brown's laboratory use in vivo mouse models of viral infection in which various genes of the host response are deleted to determine protective immune mechanisms and identify promising vaccine strategies.
Associate Professor of Biochemistry
Research focus: Mitochondrial dysfunction biomarkers, environmental stressors, and mass spectrometry.
The propagation of stress responses resulting from various environmental exposures is not well understood at the molecular level. Dr. Adamec's research program uses a combination of chromatographic separation techniques coupled with mass spectrometric characterization to define molecular interaction profiles at the proteomic level and quantify specific metabolites. These approaches have been applied to the identification and validation of disease biomarkers accompanying oxidative stress exposure. Currently, students in Dr. Adamec's laboratory are working on projects to provide systems-level datasets in cell culture models that reflect spatial and temporal cellular signaling responses to oxidative stress. Additional collaborative projects include quantification of lipid metabolites in lipotoxicity, steroid metabolites in prostate cancer, glutathione pathway intermediate flux in reactive oxygen species challenged liver cells, and post-translational modifications of DJ-1 protein.
Associate Professor of Chemical and Biomolecular Engineering
Research focus: Tissue engineering, stem cells, and liver reconstruction.
- Postdoctoral Research Fellow, Harvard Medical School and Massachusetts General Hospital, 2009
- Ph.D., Chemical Engineering and Materials Science, Michigan State University, 2007
- M.S., Chemistry, Michigan State University, 2002
- B.S., Chemistry, University of Madras, India, 1999
Key challenges in regenerative medicine, effective cancer treatment, and systemic drug delivery still remain to be answered by reconstitution of tissue microenvironments in vitro that sustain phenotypic function of primary cells. Student projects in the Kidambi laboratory capitalize on multidisciplinary collaboration with biochemists and cell biologists to generate and systematically characterize specific three-dimensional coculture constructs. Students generate constructs to test different polymer materials, randomly or specifically patterned surfaces, and individual or combined stromal-epithelial cell cultures to optimize conditions for testing basic signaling mechanisms and/or effective drug delivery.
Associate Professor of Biological Systems Engineering
Research focus: Non-viral gene delivery, synthetic extracellular matrices, and protein-cell adhesion.
- Ph.D. Biological Sciences, Northwestern University
- M.S. Biological Systems Engineering, University of Nebraska-Lincoln
- B.S. Biological Systems Engineering, University of Nebraska-Lincoln
The tissue microenvironment plays a critical role in the accessibility of embedded cells to treatment by small molecule, nanoparticle, and other non-viral forms of gene therapy. One example of graduate student projects in the Pannier laboratory focuses on understanding how tissue matrix composition and physical properties impact DNA uptake from liposome or nanoparticle delivery modes. Student projects are also designed with the goal of optimizing the format of DNA-containing nanoparticles for effective delivery in tissue constructs and in vivo.
Assistant Professor of Food Science and Technology
Research focus: Host-microbial interaction in chronic gut inflammatory disease.
- B.S., Biochemistry, Western Kentucky University
- Ph.D., Immunobiology, Iowa State University
- Post Doc, Immunology, Microbiology and Parasitology, Iowa State University
Mucosal immune function is tightly linked to microbial diversity in the gut. Understanding the dynamic interactions between cells of the host immune system and microbial strain persistence is important for combatting chronic inflammation and conditions such as Crohn's disease. Student projects in the Ramer-Tait laboratory use cell culture models and germ-free mice to investigate the mechanisms that regulate host inflammatory response to microbial colonization.
Willa Cather Professor of Biochemistry
Research focus: Mechanisms of cancer metastasis, steroid inactivation, and hyaluronan signaling and turnover.
- B.S., Biochemistry, Molecular Biology, and Biophysics (1992)
- Ph.D., Biochemistry, Molecular Biology, and Biophysics (1997)
- Post-Doctoral Researcher, Laboratory Medicine and Pathology, University of Minnesota (2002)
Prostate cancer is a disease that has documented clinical associations with mechanisms involving oxidative stress, obesity, and viral or microbial infections. Dr. Simpson's expertise in this disease complements other emphasis areas in the proposed T32 training program, which is exemplified by her service on doctoral committees of students working with mentors in each of the four areas. Her students have projects that investigate how the extracellular matrix component hyaluronan impacts cellular signaling in the prostate to promote metastasis. Her students also examine the backup control for steroid inactivation mechanisms, which the laboratory has shown are critical in mice for responsiveness to androgen deprivation therapy, the first course of treatment for clinically advanced cancer.