Dr. Dong Wang: Transcription, DNA Damage and Repair, Chemotherapy

Research Summary: Molecular Mechanisms of DNA Damage Processing Pathways

Dr. Wang’s research focuses on understanding the mechanisms of cellular responses to DNA damage. Specifically, the goals of Dr. Wang’s research are 1) to understand how DNA damage is recognized during transcription, 2) to elucidate the structural basis of DNA damage processing pathways, and 3) to pave the way for rational improvement of novel anticancer drugs.

The DNA template for transcription is not only the site of continuous attack by harmful environmental agents, but also represents a major target for cancer therapy. Alkylating anticancer agents and platinum- based chemotherapeutic drugs, such as cisplatin, are widely used and among the most effective anticancer treatments. These drugs form DNA lesions, triggering a variety of cellular processes, including transcription inhibition, DNA repair pathways, signaling pathways that activate cell cycle checkpoints and apoptosis.
Dr. Wang’s group takes a multidisciplinary approach to study key protein complexes involved in these processing pathways. Understanding how cell process these DNA lesions will help us to understand the mechanisms of drug action and resistance and pave the way for rational improvement of novel anticancer drugs.

Education: B.Sc. in Chemistry (1998) Peking University; Ph. D. in Biological Chemistry (2004) MIT, Postdoc Fellow in Structural Biology at Stanford University School of Medicine (2009).

Awards and Honors: UCSD Academic Senate Research Grant Award (2010); CIBA Young Scientist Award (2010); NIH Pathway to Independence Award (K99/R00, 2008); Leukemia & Lymphoma Society Career Development Program Special Fellow Award (2007); ASBMB Travel Award (2007&2008); ASBMB Chromosome Cycle Theme Poster Award (2007); Anna Fuller Fund Graduate Fellowship (2002).

Leadership Experience: Executive committee member, Stanford University Postdoc Association (2007-2008); Executive council member, Chinese- American Biopharmaceutical Society (2007-2008); Co-Chair, Chinese Life Sciences Postdocs and Students at Stanford (2005-2007).

Key Contributions to Pharmaceutical Sciences:

• Investigate the action and resistance mechanisms of platinum anticancer agents.
• Structural studies of transcription inhibition by a variety of anticancer agents.

Selected Recent Publications

Wang et al. (2005). Cellular processing of platinum anticancer drugs. Nature Rev. Drug Discov. 4:307- 320.

Wang et al. (2006). Structural basis of transcription: Role of the trigger loop in substrate specificity and catalysis. Cell 127:941-954.

Wang et al. (2009). Structural basis of transcription: Backtracked RNA polymerase II at 3.4 Å resolution. Science 324:1203-1206.

Liu et al. (2010). Structure of an RNA polymerase II – TFIIB complex and the transcription initiation mechanism. Science 327:206-209.

Huang et al. (2010). RNA polymerase II trigger loop residues stabilize and position the incoming nucleotide triphosphate in transcription. Proc. Natl. Acad. Sci. USA, 107:15745-15750.

Wang et al. (2010). X-ray structure and mechanism of RNA polymerase II stalled at an antineoplastic monofunctional platinum-DNA adduct. Proc. Natl. Acad. Sci. USA, 107:9584-9589.

Potential Collaborative Programs with the Pharmaceutical Industry

• Diverse array of laboratory approaches including structural biology and biochemical characterization of novel compounds for anticancer chemotherapy.