Department of Pathology


The major focus of our lab is to determine the role of chemokines, especially CXCL12, and various inflammatory molecules, such as S100A7, and anti-inflammatory molecules, such as Slit2 and cannabinoids, in pathogenesis of various diseases.

We are analyzing the role of pro-inflammatory molecule, S100A7, in breast cancer progression and metastasis. We have shown that S100A7 is highly expressed in ER-α-negative breast carcinoma. Our laboratory has shown that S100A7 enhances breast cancer growth through modulation of pro-inflammatory and pro-metastatic pathways using a novel inducible bi-transgenic mouse model. Furthermore, we have shown that S100A7 may mediate its effects by binding to receptor for advanced glycation end products (RAGE). In addition, we have shown that S100A7 may play a differential role in ERα+ and ERα- cells. We are further analyzing the role of S100A7 in ERα+ and ERα- breast cancer, especially triple-negative, using various breast cancer mouse model systems.

We also are analyzing the role of chemokine receptor CXCR4 and its ligand, CXCL12, in breast cancer progression, angiogenesis, and metastasis. We have elucidated CXCL12-induced and CXCR4-mediated novel signaling pathways that regulate breast cancer metastasis. We are further analyzing the role of CXCL12/CXCR4/CXCR7 pathways that regulate breast cancer progression and its metastasis to various organs, such as the lungs and bones, using in vivo mouse models, including CXCL12 conditional knockout mouse models.

Our laboratory also is identifying small molecular weight anti-inflammatory molecules that have potential to be used as drugs to block breast and lung cancer growth and metastasis. In this regard, we have shown that synthetic cannabinoids, which are small molecular weight molecules and do not possess psychoactive activity, inhibit breast and lung cancer growth and metastasis in vitro and in vivo using nude mice and transgenic mouse models. We also have shown that synthetic cannabinoids that bind to cannabinoid receptors CB1 and CB2 may modulate the activity of epidermal growth factor receptor and chemokine receptor CXCR4. Our laboratory is further analyzing the CB1/CB2-mediated molecular mechanism that leads to inhibition of growth and metastasis in lung and breast cancers using various transgenic and knockout mouse models.

Our laboratory recently has shown that a novel anti-inflammatory molecule, Slit2, which binds to the Robo receptor, inhibits breast tumor growth. We have shown that the Slit2/Robo complex inhibits tumor growth by modulating the beta-catenin and CXCR4-mediated signaling pathways. In addition, we have shown that Slit2/Robo possesses anti-inflammatory properties and may modulate the tumor microenvironment. We are further characterizing the role of the Slit2/Robo complex in inhibiting breast cancer progression and metastasis through modulation of the tumor microenvironment. We also are performing structural and functional studies to determine the domain on Slit2 that possesses anti-tumorigenic activity.

In addition to regulating tumor growth, we have shown that Slit2 inhibits HIV infection. We have documented for the first time an important role for Slit2 as an inhibitor of HIV-1 replication. We have shown that Slit2 attenuated the replication of diverse clinical isolates and drug-resistant strains of HIV-1. Further elucidation of molecular mechanisms revealed that Slit2 may inhibit HIV infection by blocking viral entry through modulation of the cytoskeleton. We are further exploring the Slit2/Robo1-mediated mechanisms that block HIV entry. The above studies could facilitate the development of innovative therapeutic strategies against HIV-1 infection.

Our laboratory also is analyzing the crosstalk between chemokine receptors CXCR4/CCR5 and T cell receptor in regulating HIV. We have demonstrated a novel function of SLP-76, a key adaptor protein in the TCR signaling complex, in regulating HIV-1 release in T-cells. We are further analyzing the molecular mechanisms by which T-cell receptor regulate HIV entry and release.