Antiretroviral therapy (ART) has reduced the incidence of Kaposi’s sarcoma (KS) in developed western countries. However, 95% of the estimated 40 to 60 million people infected with HIV have no access to these drugs. HIV/AIDS-associated KS is still a significant problem in the U.S. among individuals who are noncompliant due to toxicities and those who progress to AIDS without receiving drug therapy. KS is cause by Kaposi’s sarcoma-associated herpesvirus (KSHV) and is characterized as an angioproliferative tumor of vascular endothelial cells and produces rare B cell lymphoproliferative diseases in the form of pleural effusion lymphomas (PEL) and some forms of Multicentric Castleman’s Disease (MCD). Only 1-5% of cells in KS lesions actively support lytic replication of KSHV, and it is clear that cellular factors must interact with viral factors in the process of oncogenesis and tumor progression. Identifying novel host-factor determinants that contribute to KS pathology is essential for developing prognostic markers for tumor progression and metastasis as well as novel therapeutics for the treatment of KS. 

Our studies thus far have shown that galectin-3, fibulin-2 and fibulin-5 are dysregulated genes in KSHV infected dermal microvascular endothelial cells (DMVEC). All of these genes are implicated in malignancy and most likely contribute to KS pathogenesis. Thus, we are interested in evaluating galectin-3, fibulin-2, and fibulin-5 in order to determine their usefulness as diagnostic markers for KS tumor progression/metastasis, and whether they would serve as a target(s) for a novel treatment strategy. 

Our hypothesis is that downregulation of galectin-3, fibulin-2 and fibulin-5 contributes to KS pathogenesis and tumorigenesis, and that modulation of their expression in the tumor microenvironment could serve to either alter virus replication and/or reduce tumor angiogenesis, progression and metastasis. Thus reconstitution or over-expression of these genes in KS tissue and AIDS-associated pleural effusion lymphomas (PELs) could alter and/or reduce viral pathogenesis associated with KS and hence serve as molecular targets for therapeutic interventions. 

Dr. Ward's research interests include psoriasis, psoriatic arthritis (PsA), osteogenesis imperfecta (OI), lupus, hidradenitis suppurativa (HS), other inflammatory skin diseases, multi-‘omics, microbiome, and skin disease co-morbidities.

Our research focuses on how obesity and aging reshape immune responses and lead to inflammatory diseases. Immune cells are sensitive to their metabolic environment, which affects intracellular metabolism and signaling and fine-tune immune functions. We are interested in understanding how metabolic cues regulate communication between immune cells, focusing on dendritic cells and T cells. Our Lab studies how obesity and aging disturb the immune and metabolic balance and lead to excessive inflammation, including diseases such as psoriasis and asthma. We decode molecular mechanisms that link dendritic cell metabolism to tissue inflammation by combining mouse models of inflammatory skin and lung diseases with systems immunology approaches.

The immune system underlies the pathophysiology of nearly every disease, yet therapies that modulate immunity for clinical benefit have yet to reach their full potential. Our laboratory works at the interface of materials science and immunobiology to innovate solutions for immunotherapy. We are guided by the principle that the immune system must dictate therapeutic design requirements and we turn to nature for inspiration to engineer highly modular and tunable materials to accomodate these criteria. By bringing together expertise in colloid and surface engineering, advanced polymerization techniques, cell engineering, and drug delivery, we are developing molecularly engineered materials that specifically target and tightly regulate the delivery of immunomodulator drugs to the organs, cells, and intracellular pathways of the immune system. In doing so, we are making substantial process in a number of arenas.

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Organisms have evolved an array of life history strategies that reflect the tension of maximizing fitness in a world beset with predators, parasites, and hostile environments. In the Tate Lab, we are particularly interested in understanding the impact of parasites on the evolution of immune systems, and the conflicts that arise when organisms need to balance investment in immunity with other life history traits.

To this end, we couple theoretical approaches with experiments on tractable beetle systems to explore the causes and consequences of variation in both infection and immunity at the molecular, organismal, and population levels of biological organization.

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The goal of the Hurley laboratory is to reduce the death and suffering caused by prostate cancer. Cancer localized to the prostate is often curable with treatments such as surgery or radiation therapy; however, once prostate cancer has spread beyond the prostate to other organs or to the bone, it is an incurable disease. Dr. Hurley focuses on identifying both cancer cell-autonomous and non-cancer cell-autonomous genetic and molecular pathways that promote lethal prostate cancer and cause therapy resistance. She and her lab have identified SPARCL1 as a gene down-regulated in high-grade and metastatic prostate cancer that is a significant, independent prognostic marker of disease progression to metastases. SPARCL1 is a secreted extracellular matrix protein that restricts cellular adhesion, migration, and invasion. Her lab is currently examining how the loss of SPARCL1 contributes to cancer metastasis. This work also focuses on another secreted protein, Asporin. Asporin is expressed by cancer-associated stromal cells, and its increased expression is associated with worse outcomes. Findings from this research support that Asporin broadly impacts many cell types in the tumor microenvironment. Dr. Hurley and her lab are currently researching how Asporin mechanistically promotes metastatic development, and she is also interested in the utility of tumor-specific genetic alterations detected in the blood as predictors of therapy resistance.