Laura Blaha is a predoctoral trainee and a Ph.D. candidate in Biomedical Engineering. Blaha’s research seeks to develop an in vitro model of competition in soluble signaling in cancer extravasation to reveal a link between organ preference in metastasis and chemokine gradients in the extravasation microenvironment. Inflammatory breast cancer (IBC) is an aggressive cancer that results in cancer cells blocking lymphatic vessels in the skin. Because of its rapid growth, IBC is most often diagnosed after it has become metastatic, spreading to nearby lymph nodes or other body organs. Until IBC can be reliably diagnosed at a non-metastatic stage, hope for treating IBC lies in understanding and treating metastasis. Metastasis begins with primary tumor cells invading underlying stroma and entering the circulatory system. Eventually, circulating tumor cells arrest in the vasculature of a different organ and exit the vessel to establish micrometastases, a process called extravasation. Recent work to understand the mechanisms of metastasis has focused primarily on cell migration within a primary tumor and intravasation into the circulatory system. What remains to be studied are the signals that drive extravasation. The hypotheses driving these studies are: 1) Metastatic cancer cells arrested in the vasculature before extravasation can migrate in response to multiple chemokine gradients simultaneously and 2) Organ preference in metastasis is the result of certain metastatic target organs having a competitive advantage over other organs with respect to the chemokine profile they present to metastatic cancer cells arrested in the vasculature.
Christina Lisk is a predoctoral trainee in Dr. Lee Wetzler’s lab. She is matriculated in the Molecular and Translational Medicine Program within the Department of Medicine. The Wetzler lab has been investigated the role of PorB, the major outer membrane and porin isolated from Neisseria meningitidis, as an adjuvant and immunogenic modulator for two decades. Over this time, they have shown multiple unique properties of PorB, including its recognition by TLR2, its potent adjuvant activity, its ability to elicit Th1 and Th2 responses and induce increased costimualtion of T cells, increase levels of antigen specific IgG upon immunization and enhancement of antigen presenting cells (APC) trafficking to lymphoid organs. Currently the lab is exploring the induction of antigen uptake and intracellular trafficking in multiple APC types (dendritic cells, macrophages, and B cells) by PorB in vitro by utilizing confocal microscopy (including live imaging) and ELISAs. These studies will increase our knowledge of PorB, the ability to generate antigen specific antibodies, and improve its use as a vaccine adjuvant. Christina’s individual role in Wetzler’s lab research includes the effect of vaccine adjuvants in enhancing immune protectivity of immunogens. Moreover, she examines the mechanisms of TLR ligand based adjuvanticity, especially in regards to the effects on germinal centers and the cells involved in this phenomena. These topics are essential to the understanding of immune protection and related to both inflammation and microbial pathogenesis.
Cari Meisel is a predoctoral trainee in the Department of Biomedical Engineering and the Department of Pharmacology and Experimental Therapeutics working in Dr. Joyce Wong’s lab. Meisel’s work focuses on Atherosclerosis. Currently, Atherosclerosis is one of the most common cardiovascular diseases in the U.S., with aggregate inpatient hospital costs of over $10 billion in 2011 alone. While it was once thought to be a proliferative process caused simply by endothelial damage in arteries, recent work has indicated that inflammation acts as an important regulatory process at each stage of atherosclerosis. As such, there has been a recent focus on the use of anti-inflammatory therapeutics for treatment of atherosclerosis. Several such therapeutics (e.g. methotrexate, darapladib) have been examined in clinical trials for treatment of atherosclerosis; however, these compound were either shown to be ineffective (e.g. darapladib), or demonstrate significant systemic side effects (e.g. methotrexate). Therefore, Meisel works to develop a targeted nanocapsule capable of carrying an anti-inflammatory compound specifically to an atherosclerotic plaque. This approach would allow for treatment of the inflammatory processes causing the plaque while eliminating the majority of the negative systemic side effects observed with compounds such as methotrexate.
George Papadopoulos is a predoctoral trainee in Dr. Caroline Genco’s laboratory and a third year PhD candidate in the Molecular and Translational Medicine Program. Dr. Genco’s lab is located on the Tufts Medical Campus, where George is currently enrolled as a visiting student in the immunology graduate program. Research in the Genco lab focuses on the role of the innate immune system in pathogen-induced chronic inflammation using Porphyromonas gingivalis as a model organism. P. gingivalis is a Gram-negative, oral pathogen implicated in periodontal disease, a highly prevalent chronic inflammatory disease characterized by the destruction of tooth supporting tissue. In addition to pathology at the initial site of infection, mounting evidence support a role for P. gingivalis in the development and progression of systemic diseases including atherosclerosis. The Genco lab developed a model in which oral infection of atherosclerosis-prone mice induces both local (oral bone loss) and systemic (atherosclerosis) inflammation. Using transgenic mice and defined bacterial mutants, they have defined both host and pathogen specific mechanisms linking oral infection with P. gingivalis to local and systemic immunopathology. George’s thesis work focuses on defining the role of type I interferon in P. gingivalis-induced chronic inflammation.
Luis Agosto is a postdoctoral trainee in the laboratory of Dr. Andrew Henderson. Luis received his Ph.D. in Cellular and Molecular Biology with an emphasis in Virology from The University of Pennsylvania (UPENN). His project currently focuses on how bacterial exposure influences macrophage function and inflammation in the context of HIV infection which has implications for HIV associated diseases of multiple organ systems. Tissue macrophages are known to be important mediators of bacterial clearance but their functions are dysregulated in the context of co-infections with HIV. Periodontal disease caused by the anaerobic bacterium Porphyromonas gingivalis is a common opportunistic infection resulting from untreated HIV infection and provides a model to interrogate the dysregulation of macrophage immune function, inflammatory disease progression and HIV replication during co-infections. Luis is investigating the effect of P. gingivalis in the replication of HIV in monocyte-derived macrophages and how the immune functions of macrophages are affected by co-infection of both pathogens. He finds that co-infections of macrophages with P. gingivalis results in a significant impairment of HIV replication. This impairment in viral replication is due in part to a significant decrease in the expression of integrated HIV. His group also finds that this impairment in HIV expression correlates with a change in the anti-inflammatory phenotype of macrophages. Importantly, the repression of HIV expression can reversed using phorbol esters suggesting that this may be a novel mechanism for establishing HIV latency in primary macrophages. These observations suggest that co-infections of macrophages with HIV and bacterial pathogens may influence the establishment and maintenance of latent HIV in macrophages.
Dequina Nicholas is a postdoctoral trainee in the Nikolajczyk lab. Dequina works on a joint project between the Nikolajczyk and Denis labs on the role that obesity and type 2 diabetes-associated inflammation plays in disease pathogenesis and cancer. She completes cytokine profiling from immune cells from multiple human tissues (blood, adipose tissue, breast adipose tissue) and spearheads cutting-edge multivariate analyses to define inflammatory signatures of obesity stages with follow up mechanistic work on candidates that may shift lymphocyte metabolism in obesity confounded with inflammation. She also determines how inflammatory signatures facilitate the transition from obese/metabolically healthy to obese/type 2 diabetes by treating immune cells from healthy people with obesity-associated cytokine “signatures” alone, or in the presence of adipocytes. She similarly tests the impact of inflammatory signatures on breast ductal cells to identify direct links between obesity and breast cancer.