Ningling Kang, Ph.D., studies cellular and molecular mechanisms by which hepatic stellate cells, the liver resident pericytes, regulate tumor implantation and metastatic growth in the liver. The long-term goal of Dr. Kang's team is to uncover mechanisms and identify therapeutic targets within the hepatic tumor microenvironment for reducing tumor progression and metastasis.
Dr. Kang's team uses primary hepatic stellate cell culture, a hepatic stellate cell/tumor cell co-implantation mouse model, an experimental liver metastasis mouse model, and gene knockout mouse models. Additionally, she and her team members utilize noninvasive in vivo xenogen imaging techniques to detect and quantitate tumor implantation and growth in mice.
Dr. Kang's research has been funded by a research project grant from the National Cancer Institute and other organizations. She is a member of Mayo Clinic Center for Cell Signaling in Gastroenterology and Mayo Clinic Cancer Center.
- How do IQPAP1/Rac1/VASP protein complexes regulate TGF-beta receptors and TGF-beta activation of hepatic stellate cells into myofibroblasts? Although both IQGAP1 and VASP are actin regulatory proteins, IQGAP1 and VASP play contrasting roles in the regulation of hepatic stellate cell activation in vitro. IQGAP1 of hepatic stellate cells suppresses their activation while VASP promotes their activation.
- Do Smurf1 and Smurf2 regulate the hepatic tumor microenvironment and liver metastatic growth? Smurfs are the E3 ubiquitin ligases that promote the degradation of TGF-beta receptors. It is undetermined if Smurf1 and Smurf2 regulate hepatic stellate cell function and the hepatic tumor microenvironment.
- Creating conditional knockout mouse lines. Two mouse lines in which IQGAP1 or VASP is deleted specifically in hepatic stellate cells will be created. These animal models will be used for further in vivo liver metastasis studies.
Significance to patient care
Many cancers show a preference for liver metastases. Dr. Kang's research focused on bidirectional interactions between tumor cells and the hepatic tumor microenvironment could help to develop strategies to target the liver-specific mechanisms for preventing and treating metastatic liver diseases.
- Sheila Sherlock Clinical and Translational Research Award in Liver Diseases, American Association for the Study of Liver Diseases, 2006-2007
- Howard Temin Award (K01 Grant), National Cancer Institute, 2007-2012