Research Topics

Project 1: Galectin-1 as a novel therapeutic target for lung cancer

Galectins can directly influence cell transformation, invasion, angiogenesis and metastasis. Furthermore, elevated levels of Gal-1 contribute to chemoresistance in lung cancer cells. Since malignant transformation is not simply a disease of abnormally proliferating epithelial cells, but rather encompasses complex interactions between the neoplastic cells and the tumor microenvironment, targeting a molecule that participates in multiple aspects of neoplastic transformation could be a highly effective therapeutic strategy. Since Gal-1 is a secreted protein, it is an ideal target for small molecule inhibitors. Currently, there have been limited attempts at targeting this key molecule. Using rational drug design and state of the art software, the Molecular Modeling Core at our institution has identified several hundred potential small molecule inhibitors from a database of over 4,500,000 publicly available compounds that block Gal-1 binding to its substrates. Several of these potential inhibitors have been commercially obtained and will be tested for their ability to block Gal-1 mediated cell adhesion in a multiplex screening process. These candidate Gal-1 inhibitory compounds will be rigorously tested in order to identify the most potent and efficacious Gal-1 antagonist in in vitro lung cancer models. If successful, this novel strategy can be fairly rapidly translated to the clinic where it would greatly impact lung cancer treatment and patient survival.

Project 2: Inhibition of Tumor Growth by Inducing Anti-tumoral T-cell Immune Responses with Adenosine Deaminase Enzyme

Tumor-derived secreted and cell surface effectors elicit immunosuppressive signals resulting in increased T regulatory (Treg) lymphocytes among other suppressive mediators. T regulatory cells have been proposed to contribute to creating a suppressive milieu that protects tumor cells from immune destruction. Although these effector pathways have been the focus of drugs designed to break immune tolerance in late stage cancer patients, immunotherapeutic targeting strategies in cancer patients have largely failed to improve overall survival. Recent studies have shown that adenosine is highly expressed and secreted from T regulatory cells and acts to potentiate their pro-tumoral immunosuppressive potential. Adenosine-regulated immunosuppressive mechanism limits promising cancer therapies using anti-tumor T cells. We hypothesize that solid tumors are protected from anti-tumor T cells because of the immunosuppressive signaling via T cell-expressing A2A adenosine receptor (A2AR) activated by extracellular adenosine produced abundantly within the tumor microenvironment by the immunosuppressive T regulatory cells. Recently published data support our hypothesis that anti-tumoral T cells are inhibited by extracellular adenosine because of A2AR-triggered increase in intracellular levels of cAMP. Increase of intracellular cAMP induces Protein Kinase A-mediated signaling changes, which in turn, diminish T cell signaling and anti-tumoral T effector responses. Blockade of adenosine activity with drugs such as ADAGEN will exert a powerful adjuvant effect on T cells and induce the rejection of many established primary tumors. We predict that therapeutic targeting the Adenosine (T regulatory Cell) ---- A2AR (anti-tumoral T effector cells) signaling with adenosine deaminase (ADA) activity will be sufficient to drive T cell-mediated immune responses from a pro-tumoral toward an anti-tumoral phenotype leading to an efficacious anti-cancer immunity.

Professional Memberships

1. American Medical Student Association (AMSA), 2012-present
2. Student National Medical Association: SNMA, 2012-present

"1^st & 2nd year IPIBS Students usually do not have much information which can suit for the following subheadings in their profile page. They gain numerous skills and publications during the period of PhD program."