Martin E. Hemler

Martin E. Hemler

Professor of Pathology
Martin E. Hemler

Research in Dr. Hemler's laboratory is focused on novel mechanisms which affect tumor cell interactions with leukocytes, endothelial cells and fibroblasts within the tumor microenvironment. Specific projects are as follows:

1. EWI-2 (IgSF8) provides a novel link between melanoma and the tumor microenvironment. EWI-2 is a cell surface protein that is upregulated on malignant melanoma cells, and contributes to human melanoma xenograft growth in mice. To identify and characterize a potential EWI-2 counter-receptor, we prepared a tetrameric EWI-2 probe. Thus we obtained evidence for a EWI-2 counter-receptor on the surface of fibroblasts, endothelial cells and myeloid cells. Furthermore, we discovered that EWI-2 tetramer can trigger the selective production of a few key chemokines by monocytes. Hence, we hypothesize that EWI-2 on melanoma cells binds to a counter-receptor on fibroblasts, endothelial cells and myeloid cells within the tumor microenvironment, thus leading to favorable ‘pro-tumor' conditions. Efforts are currently underway to identify the EWI-2 counter-receptor. In the longer term, we suspect that inhibition of EWI-2‒counter-receptor interaction may be therapeutically beneficial for the treatment of melanoma.

2. The enzyme DHHC3 regulates tumor cell recognition by immune cells. Removal of the enzyme DHHC3 from breast and prostate tumor cells results in markedly diminished in vivo xenograft growth, but has minimal effect on in vitro cell growth. Diminished growth in vivo is accompanied by an increase in the ratio of M1/M2-type tumor associated macrophages, and/or by an increase in the presence of myeloid-derived suppressor cells. A mass spectrometry/proteomics approach has led to the identification of ~20 protein substrates that undergo DHHC3-dependent palmitoylation. Efforts are underway to identify which specific ‘loss of palmitoylation' events in the tumor are most critical with respect to regulating the immune cell microenvironment.

Contact Information

Dana-Farber Cancer Institute
Dana Bldg, Rm. 1430
44 Binney Street
Boston, MA 2115
p: 632-3410

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