Yu-Ying He, Ph.D.

APPOINTMENTS

  • Associate Professor, Department of Medicine - Section of Dermatology, Cancer Research Center, Committee on Cancer Biology, Committee on Molecular Medicine/MPMM

EDUCATION

Ph.D., Chinese Academy of Sciences, 2000

CONTACT INFORMATION

The University of Chicago
AMB N007M / MC 5067 
5841 South Maryland Ave.
Chicago, Illinois 60637

yyhe@medicine.bsd.uchicago.edu

Phone:  (773) 795-4696

Website (Department of Medicine)

RESEARCH SUMMARY

Genetic and Environmental Determinants of Genomic Stability in Skin Cells

Our research addresses the fundamental question of how cells respond to radiation and chemicals from internal or external sources to cause cancer, with a focus on skin cancer. We use in vitro systems, clinically relevant animal models, genetically modified mouse models, and human patient samples to elucidate how intrinsic and extrinsic factors regulate DNA repair, DNA damage response, and cellular homeostasis in order to understand cancer susceptibility.  Because skin is an epithelial tissue, our findings are relevant to cancers of other epithelial tissues, and our research has the potential to identify new targets and strategies to improve prevention and treatment for both skin and other epithelial cancers. Our long-term goal is to identify previously unrecognized, therapeutically accessible molecular regulatory networks that predict susceptibility to skin cancer, and to improve our ability to prevent and treat it.

(i) Role of autophagy and p62 in tumor initiation and progression. Macroautophagy (hereafter autophagy) is a catabolic process by which cellular proteins, cytoplasm, and organelles are captured and targeted for proteolytic degradation in lysosomes. Autophagy dysfunction is associated with multiple human diseases, such as neurodegeneration, microbial infection, metabolic diseases, cardiovascular diseases, aging, and cancer. The multidomain protein p62/A170/SQSTM1 (hereafter p62) has been shown to be both a selective autophagy substrate and an autophagy adaptor protein that acts as a link between ubiquitination and autophagy. Autophagy is a pleiotropic cell survival mechanism with both pro- and anti-tumor effects. We focus on elucidating the regulatory and functional role of autophagy in skin carcinogenesis and cancer progression.

(ii) Molecular control of DNA damage response. Two crucial DNA damage response processes in tumor suppression are apoptosis and senescence, i.e. when the DNA damage burden is large, cells "commit suicide", or terminally differentiate. Dysregulation of apoptosis or senescence promotes tumor initiation and progression. Our research is centered on understanding the molecular basis for controlling DNA damage response.

(iii) Molecular control of DNA repair. We focus on investigation of the molecular mechanisms controlling the versatile DNA repair pathway nucleotide excision repair (NER). NER eliminates a wide variety of helix-distorting base lesions induced by ultraviolet B (UVB) radiation, tobacco smoking, cisplatin and oxidative damage. Since key NER proteins are difficult to target directly, identification of upstream regulators has the potential to provide valuable targets for enhancing NER and therefore tumor suppression. However, the molecular signaling pathways regulating NER has been poorly understood. We focus on the molecular mechanisms in regulating NER capacity. These findings have the potential to yield safe and efficient targets to improve DNA repair capacity and thereby to prevent skin cancer and other epithelial cancers.

(iv) Extrinsic control of DNA repair and DNA damage response. The mechanisms by which extrinsic factors cause skin cancer can define molecular targets for better prevention and therapy. Organ transplant recipients (OTRs) have a 65 to 250-fold increased risk of developing skin squamous cell carcinoma caused by treatment with immunosuppressants, and immunosuppression has been widely assumed to be the major extrinsic cause for increased skin cancer susceptibility. However, the molecular mechanism by which this occurs was unknown. We focus on the cell-autonomous molecular mechanism of skin tumorigenesis caused by immunosuppressive drugs. These findings have the potential to provide new opportunities and targets for developing better strategies to reduce the burden of this devastating disease in OTRs, without compromising the life-saving attributes of immunosuppressive drugs

Research Papers in PubMed