Yiyong (Ben) Liu, PhD

• PhD in Biochemistry and Molecular Biology, East Tennessee State University
• Postdoctoral Training, HHMI, Duke University Medical Center

Research in my laboratory focuses on stress responses and their relationships with aging and cancer. Living organisms are constantly challenged by endogenous insults as well as environmental agents. Mounting appropriate stress responses to counter these attacks is key to health and longevity. We study DNA damage responses, immune responses, and how these responses relate to aging and oncogenesis.

Our current work includes the following three areas:

• Age-related alterations in neuroimmune regulation

Two of the main characteristics of the aging of the immune system are chronic activation of the innate immune system that results in low-grade inflammation known as inflammaging and increased susceptibility to pathogen infections. If an activated immune system is a requisite for fighting infections, what explains the increased susceptibility to infections in the elderly with a chronically active immune system? Our recent study in C. elegans revealed that old worms had elevated expression of immune genes (likely reflecting inflammaging) as well as genes involved in neural signaling, especially in neural circuits that suppress immunity. We hypothesize that aging-associated elevation of the basal immune response trigger immunosuppressive neural circuits that act as a compensatory mechanism to maintain immunological homeostasis, which in turn inhibits the immune response to pathogen infections. To test this hypothesis, we are investigating age-related changes in neuroimmune regulation and how such changes may contribute to immune aging and aging-associated diseases.

• Roles of collagens in stress resistance and longevity

We have demonstrated that functional loss of C. elegans NPR-8, a G protein-coupled receptor related to the mammalian neuropeptide Y receptors, increases worm lifespan at 25°C but not at 20°C or 15°C. The increased resistance to warm temperature is achieved through the upregulation of collagen genes and is controlled by specific neurons. Independent research showed that collagen production and function decline with age, and that elevated collagen expression is a shared feature of multiple conserved longevity pathways and essentially every longevity intervention. Collagen expression also increases survival against oxidative stress and pathogen infection. These findings, together with ours, suggest that collagen expression promotes stress resistance and longevity and that such promotion is regulated by the nervous system. We are currently investigating the molecular and cellular mechanisms underlying the influence of NPR-8-regulated collagen expression on stress resistance and longevity.

• Age-dependent oncogenesis

Cancer is largely an aging-related disease but is rarely studied in the context of aging. DNA damage accumulates during natural aging, which could transform normal cells into highly mitotic malignant cells that form tumors. In collaboration with Dr. Yue Zou at the University of Toledo, we have established a mouse model in which a mitochondria-specific isomeric form of ataxia telangiectasia and Rad3-related protein (ATR) is oncogenic, increases in cells as DNA damage accumulates during aging, and eventually drives spontaneous oncogenesis. Using this model, we are currently characterizing epigenetic changes in age-dependent oncogenesis.

 

• Palani SN, Sellegounder D, Wibisono P, and Liu Y. The longevity response to warm temperature is neurally controlled via the regulation of collagen genes. Aging Cell 2023, Accepted.
• Wang AJ, Wibisono P, Geppert BM, and Liu Y. Using single-worm RNA sequencing to study C. elegans responses to pathogen infection. BMC Genomics 2022, 23:653.
• Wibisono P, Wibisono S, Watteyne J, Chen C, Sellegounder D, Beets I, Liu Y*, and Sun J*. Neuronal GPCR NMUR-1 regulates distinct immune responses to different pathogens. Cell Reports 2022, 38(6):110321. *Co-corresponding author.
• Liu Y* and Sun J*. Detection of pathogens and regulation of immunity by the Caenorhabditis elegans nervous system. mBio 2021, 12(2):e02301-20. *Co-corresponding author.
• Wibisono P, Liu Y, and Sun J. A novel in vitro Caenorhabditis elegans transcription system. BMC Molecular and Cell Biology 2020, 21(1):87.
• Sellegounder D, Liu Y, Wibisono P, Chen C, Leap D, and Sun J. Neuronal GPCR NPR-8 regulates C. elegans defense against pathogen infection. Science Advances 2019, 5(11):eaaw4717.
• Sellegounder D*, Yuan CH*, Wibisono P, Liu Y, and Sun J. Octopaminergic signaling mediates neural regulation of innate immunity in Caenorhabditis elegans. mBio 2018, 9(5):e01645-18. *Co-first author.
• Liu Y and Sun J. G protein-coupled receptors mediate neural regulation of innate immune responses in Caenorhabditis elegans. Receptors & Clinical Investigation 2017, 4:e1543.
• Liu Y, Sellegounder D, and Sun J. Neuronal GPCR OCTR-1 regulates innate immunity by controlling protein synthesis in Caenorhabditis elegans. Scientific Reports, 2016, 6:36832-36845.
• Sun J, Liu Y, and Aballay A. Organismal regulation of XBP-1-mediated unfolded protein response during development and immune activation. EMBO Reports, 2012, 13:855-860.
• Liu Y, Kadyrov FA, and Modrich P. PARP-1 enhances mismatch dependence of 5’-directed excision in human mismatch repair. DNA Repair, 2011, 10:1145-1153.
• van Oers JM, Rao S, Werling U, Liu Y, Genschel J, Hou H Jr, Sellers RS, Modrich P, Scharff MD, and Edelmann W. PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance. Proc Natl Acad Sci USA, 2010, 107:13384-13389.
• Liu Y, Fang Y, Shao H, Lindsey-Boltz L, Sancar A, and Modrich P. Interactions of human mismatch repair proteins MutSα and MutLα with proteins of the ATR-Chk1 checkpoint pathway. J Biol Chem, 2010, 285:5974-5982.
• Liu Y, Wang Y, Rusinol A, Sinensky M, Liu J, Shell SM, and Zou Y. Involvement of xeroderma pigmentosum group A (XPA) in progeria arising from defective maturation of prelamin A. FASEB J, 2008, 22:603-611.
• Liu Y and Zou Y. New insights into the roles of XPA and RPA in DNA repair and DNA damage responses. Current Chemical Biology, 2007, 1:151-160.
• Wu X, Shell SM, Liu Y, and Zou Y. ATR-dependent checkpoint modulates XPA nuclear import in response to UV irradiation. Oncogene, 2007, 26:757-764.
• Liu Y, Rusinol A, Sinensky M, Wang Y, and Zou Y. DNA damage responses in progeroid syndromes arising from defective maturation of prelamin A. J Cell Sci, 2006, 119:4644-4649.
• Zou Y, Liu Y, Wu X and Shell S.M. Functions of human replication protein A (RPA): From DNA replication to DNA damage and stress responses. J Cell Physiol, 2006, 208:267-273.
• Liu Y, Kvaratskhelia M, Hess S, Qu Y, and Zou Y. Modulation of replication protein A function by its hyperphosphorylation-induced conformational change involving DNA binding domain B. J Biol Chem, 2005, 280:32775-32783.
• Liu Y, Yang Z, Utzat CD, Liu Y, Geacintov NE, Basu AK, and Zou Y. Interactions of human replication protein A with single-stranded DNA adducts. Biochem J, 2005, 385:519-526.
• Liu Y, Liu Y, Yang Z, Utzat C, Wang G, Basu AK, and Zou Y. Cooperative interaction of human XPA stabilizes and enhances specific binding of XPA to DNA damage. Biochemistry, 2005, 44:7361-7368.