HyeonJoo Cheon, Ph.D.
Address
4100 John R St. Detroit, MI, 48201Office address
HWCRC Rm. 640.1
Department
Oncology
Research interests
The molecular mechanisms and the impact on cancer therapy of
• Cancer cell-produced type I-interferon/ Interferon addiction of cancer cells
• Cancer cell-intrinsic/ immune-independent function of PD-L1
• Combination therapy using radiation/ chemotherapy and anti-PD-L1
Research description
The Cheon Lab is interested in how cancer cells regulate their own synthesis of type-I interferon (IFN-I) and how they control their responses to IFN-I in the tumor microenvironment. Cancer cell-intrinsic IFN-I synthesis and response impact the effectiveness of radiation therapy, chemotherapy, and immunotherapy. IFN-I contributes to both cell death and survival depending on its strength and duration of stimulation. Acute responses to IFN-I are induced by therapeutic levels of intense DNA damage, leading to cell death through expression of cytotoxic IFN-stimulated genes (ISGs). On the other hand, chronic responses to low levels of IFN-I, induced by repeated exposures to low-level DNA damage, render cells more resistant to DNA damage by inducing pro-survival ISGs, the IFN-related DNA damage resistance signature (IRDS). Some cancer cells constitutively produce and are addicted to their own IFN-I (IFN addiction). They undergo spontaneous apoptosis when their IFN responses are blocked. Interestingly, programmed cell death ligand 1 (PD-L1), often expressed in cancer cells to avoid T cell attack, regulates both sides of IFN-I responses. High levels of PD-L1 inhibit acute cytotoxic IFN-I responses and sustain chronic pro-survival IFN-I responses, protecting cancer cells from DNA damage.
Our current research is focused on: i) determining effective therapeutic strategies that combine DNA damaging agents, IFN-I, and anti-PD-L1 antibodies, which can target cancer cell-intrinsic mechanisms, as well as immune-dependent mechanisms; and ii) elucidating the molecular and cellular mechanisms of how PD-L1 inhibits the JAK-STAT pathway in response to IFN-I, which induces cell killing, and iii) the mechanisms of how PD-L1 facilitates constitutive STING (stimulator of interferon genes) activation that leads to low levels of IFN-I synthesis in cancer cells, inducing chronic pro-survival responses. In the long run, our research will contribute to innovative approaches to treat therapy-resistant tumors using knowledge of IFN-I synthesis and signaling in cancer cells, which has not been previously understood because of the complexity of IFN biology.
PubMed - my bibliography
Education/training
B.S. 1993 Yonsei University, Seoul, South Korea
M.S. 1996 Yonsei University, Seoul, South Korea
Ph.D. 2004 Korea University, Seoul, South Korea
Postdoc 2009 Cleveland Clinic, Cleveland, OH