Dr. Hong Ling

Professor
Ph.D., University of Alberta
Postdoctoral Fellow, NIH 
Office: Medical Sciences Building Rm. 334
Phone: 519.661.3557
E-mail: hling4@uwo.ca
Ling Lab Website

Awards

  • Canada’s Premier Young Researcher: Peter Lougheed/CIHR New Investigator Award (2004)
  • Terry Fox New Investigator Research Award (2004)
  • CIHR New Investigator Salary Award (2004)
  • Canada Foundation for Innovation New Opportunities Fund Award (2005)
  • Early Researcher Award, Ontario Ministry of Research and Innovation (2008)

Research Interests

Research in my laboratory focuses on identifying the molecular mechanisms of DNA damage and how this is properly managed in cells. In particular, we study biological responses to DNA damage and mutagenesis caused by endogenous and environmental DNA-damaging agents, which have broad implications in cancer. To reach our research goals, we use X-ray crystallography to determine protein structures, combined with molecular biology, cell biology, protein chemistry and other biophysical methods. We are currently working on the following projects:

Translesion DNA synthesis and its regulation

DNA damage (lesions) blocks normal DNA replication and poses serious problems for cell survival. An important DNA damage tolerance mechanism is translesion DNA synthesis (TLS), which allows DNA replication to bypass the damaged sites. This process requires specialized DNA polymerases called translesion DNA polymerases. Most of these polymerases belong to the Y-family of polymerases, which are error-prone and cause mutations; hence, these enzymes need to be tightly regulated. Malfunction of their low-fidelity replication results in elevated mutation rates in cells, which lead to the onset of cancer. We study the structure-function of Y-family polymerases and their interactions with TLS regulatory proteins to reveal the molecular mechanism of TLS and its regulation. (This research has been funded by the CIHR.)

Human Y-family polymerases and carcinogenesis/drug resistance

Carcinogenesis and anti-cancer drug resistance are focuses of cancer research. Both processes are associated with translesion DNA synthesis (TLS). Polycyclic aromatic hydrocarbons, such as Benzo[a]pyrene (BP), are ubiquitous environmental pollutants and carcinogens. Cisplatin is one of the most widely used chemotherapeutic drugs for human cancers. These DNA damaging agents form BP- and cisplatin adducts that lead to elevated mutagenesis and drug resistance, respectively, through TLS. We work on understanding the structure-function relationship of translesion DNA polymerases with the cancer-related DNA lesions in order to identify the molecular events in TLS that cause carcinogenesis and cancer drug resistance. (This research was funded by NCIC and is currently funded by the CRS.)

Error-free DNA lesion bypass

The error-free DNA damage tolerance pathway bypasses DNA lesions without increasing the mutation rate. Homologous recombination (HR) or DNA strand exchange is required for error-free lesion bypass, but the molecular events involved are not clear. Recently, some key genes have been identified that are involved in the error-free lesion bypass. The gene products (proteins) are required for efficient HR and facilitate DNA strand switching. We work on structure-function studies of these proteins to reveal the molecular mechanism of error-free lesion bypass. (This project is funded by an NSERC Discovery Grant.)

Teaching

  • 3383f - Introduction to Biochemical Research
  • 4410a - Molecular Biology of DNA and RNA
  • 4425b - Proteomics and Protein Biotechnology
  • 4440a - Protein Structure, Analysis and Design
  • 4400f - Membrane Structure and Function
  • 4483e - Honor Thesis Research Project and Seminar (course coordinator)
  • 9523b - Advanced Analytical Methods in Biochemistry
  • 9525b - Synthetic Biology 

Publications

Available on Publication Page of Ling Lab Website