Lingeng Lu, MD, PhD

1. Genetic, epigenetic and environmental factors in cancer risk and progression

As a chronic disease, human cancer has a complex etiology, resulting from the comprehensive consequence of genetic, epigenetic and environmental factors. Genetic and epigenetic aberrations frequently occur in malignancies. In this project, we aim to evaluate the significance of genetic variations, gene expression and non-coding RNA (miRNAs and lncRNAs) and DNA methylation, RNA methylation-associated genes, cancer stem cell-associated genes and environmental factors, as well as their interactions in cancer etiology, diagnosis and prognosis using population-based case-control studies (endometrial, liver, bladder, brain, gastric, esophageal, pancreatic cancer) and case cohort studies. We also investigate the mechanisms of functional variants via the approaches such as DNA/RNA secondary structures, eQTL and pQTL. The long-term goal is to individualize prevention and treatment of human cancer.

2. Circulating exosomes and HIV-associated neurological disorders and cancer

Exosomes are bilayer membranous nano-vesicles actively released into the circulation by living cells, and contain enriched bioactive molecules (proteins, DNA/RNA, lipids), mirroring the cells of origin and mediating cell-to-cell communications in a hormone manner. We aim to investigate the associations of exosomal bioactive molecules in plasma (non-coding RNAs and proteins) and HIV-associated neurological disorders (in collaboration with Dr. Spudich at Neurobiology and Dr. Emu at Infectious Diseases), and the risk of cancer. The long-term goals are to develop novel strategies to prevent neurological impairment of HIV patients during antiretroviral therapy (ART) for the HIV project, and to early detect human cancer, and to monitor the disease progression via liquid biopsy.

3. Exercise and healthy living in breast cancer and ovarian cancer survivors

Exercise and healthy eating are beneficial effects on human health. We aim to investigate the effects of exercise and healthy lifestyles intervention on the risk factors and immunosuppression of breast and ovarian cancer in the survivors. The long-term goal is to prevent the cancers and reduce the mortality by modifying lifestyles.

4. Immune checkpoints and cancer progression

Immune escaping is a hallmark of tumors. Immune responses in tumors depend on neoantigen presentation, T cell infiltration and effector T cell activation. We aim to examine the associations between microenvironmental factors, immune checkpoints and T cell activation, and tumor progression. The long-term goal is to develop novel strategies to individualize immunotherapy.

5. Telomere, aging and cancer

Telomeres are the repeat sequences at the end of chromosomes for genome stability and integrity, and get shorter each time a cell divides. When telomere length reaches a critical threshold, the cell enters senescence and stops growth. Telomere lengthening machinery maintains the telomere length in malignancies, allowing an limited cellular lifespan. We aim to understand how environmental factors and lifestyles affect telomere length, how telomere machinery associates with aging and cancer progression and treatment.