|
Dr. Qin received his M.D. and Ph.D. in Investigative Dermatology from Beijing Medical University, People’s Republic of China in 1993. Dr. Qin was trained in the Dermatology Department at the University Hospital of Zurich, Switzerland for cutaneous T cell lymphoma research. In 1998 he was recruited as Research Associate to Skin Cancer Program of the Oncology Institute at Loyola University of Chicago, and was appointed Research Assistant Professor in 2002.
Dr. Qin’s research is in the area of defining targets for molecular therapy of skin cancer. His past research has elucidated the abnormalities of several transcription factors (AP-1, cMyc and STAT) in cutaneous T cell lymphoma and dissected the role of NFkB and p53 in keratinocyte apoptosis induced by death receptor ligation and UV irradiation. His ongoing study is focused on understanding the signals governing the drug resistance of human melanoma and exploring new targets for novel therapies. He has documented that targeting Notch pathway by gamma secretase inhibitor (GSI) and interrupting proteasome function by proteasome inhibitors can selectively kill tumor cell with specific induction of NOXA, a BH3-only proapoptotic protein. These studies may promise new therapeutic approaches for human melanoma.
Cutaneous Oncology Program
Dr. Jian-zhong Qin works together with Dr. Brian J. Nickoloff studying the molecular mechanisms of drug resistance and pursuing novel therapeutic targets in melanoma.
Malignant melanoma presents a therapeutic challenge. At present no effective therapy exists for metastatic melanoma because at this stage the tumor cells are highly resistant the conventional chemotherapy. This drug resistance in melanoma is most likely caused b y dysregulation of apoptotic processes. Therefore, identification of novel treatment agents targeting critical apoptotic pathways in melanoma is urgently needed.
Our current work focuses on two projects
- Overcoming melanoma drug resistance by targeting proteasomes
We have observed that proteasome inhibitors preferentially induced significant apoptosis in human melanoma cells, both in-vitro and in-vivo, whilst sparing normal melanocytes. They selectively induce the BH3-only protein NOXA in mela noma cells, but not normal melanocytes, and this induction of NOXA occurred in a p53-independent fashion. The kinetics of NOXA induction correlate with the activation of apoptotic machinery in melanoma cells. Blocking induction of NOXA using an antisense oligonucleotide significantly reduces the apoptotic response. We are now further characterizing the signal pathways leading to tumor selective killing and Noxa induction by targeting proteasome in melanoma.
- Targeting the Notch signal pathway for melanoma treatment
The Notch receptor and signal pathway controls differentiation, proliferation and apoptosis in a variety of different cellular contexts. Our preliminary data revealed strong expression of Notch 1, 2, 4 receptors in most primary and metastatic melanoma tissues, indicating that Notch signaling may play a role in human melanoma. Strategies targeting the Notch pathway could potentially be used to improve the effectiveness of melanoma treatment. We are currently studying the validity of the Notch pathway as a new therapeutic target in melanoma. By inhibiting the Notch signal pathway with a variety gamma secretase inhibitors and specific RNA interference (RNAi) techniques, we detect melanoma cell viability both in vitro and in vivo. We also dissect the signal pathways of tumor cell death after interrupting Notch signaling.
Publications
View a partial list of
Dr. Qin's publications through the National Library of
Medicine's PubMed online database.
|
