研究项目和附属机构
研究兴趣
博士的长期目标. Wong's research are to develop a translational research program that spans the bench and the clinic to understand the molecular, cellular and circuit bases of neuropsychiatric and neurodegenerative disorders, 尤其是那些伴有代谢紊乱的患者. Type 2 diabetes and other metabolic consequences of obesity are associated with higher rates of depression, 焦虑和痴呆. 目前关注的焦点是. Wong's lab include: Characterization of novel biomarkers in major depression and the role of specific genes or pathways in depression, 包括炎性体信号, 表观遗传标记, 可变剪接, 还有肠道微生物群.
我们目前有4个项目:
1) To determine the specific role(s) of PHF21B (plant homeodomain finger protein 21B) in neuronal function relevant to social recognition impairment; this is relevant because social cognitive impairments are a central feature of several neurodegenerative, neuropsychiatric, 神经发育(e.g., autism spectrum and attention deficit hyperactivity disorder) conditions, and also occur following acute brain damage after traumatic brain injury and stroke.
2) A innovative research line focused on investigating the interface between neuroinflammation and serotonin signaling in chronic stress.
3) A line of research focusing on the role of pre-mRNA splicing in the pathophysiology of chronic stress.
4) A line of research focused on the role of 可变剪接 in the cognitive decline of Alzheimer’s disease (AD) and aging.
协会/会员
EDUCATION
之前的预约
RESEARCH ABSTRACT
My research has resulted in over 200 publications, cited over 13,000 times (h-index 57). I have contributed primarily to three lines of investigation, as follows:
- My lab has a strong track record studying the genomics of antidepressants and major depressive disorder, which started in 2000 as part of the National Institute of General Medical Sciences, NIH药物基因组学研究网络(PGRN). In that project, we studied a Mexican-American population with major depression in Los Angeles. Our group conducted the first NIH-funded studies of antidepressant pharmacogenomics in Hispanics, with findings that have been independently replicated. We have examined candidate systems and pathways, including corticotropin-releasing hormone (CRH)及CRH受体1 (CRHR1)、脑源性神经营养因子(BDNF)及其受体， NTRK2. 我们重新测序了几个基因，包括 BDNF, NTRK2, and CRHR1, and discovered a substantial number of new variants. Recently, we have identified several genes that may be associated with major depression and replicated the PHF21B gene. These new functional genetic markers have provided the basis for a provisional patent, which we are now studying at the functional neuroscience level.
- We have contributed to understanding the role of neuroendocrine/neuroimmune aspects of MDD. We have studied cytokines and immune mediators in the central nervous system, with implications for the underlying biology of major depressive disorder, and published work in this area include the localization of gene expression for interleukin 1 receptor antagonist (Il1rn)、I型白细胞介素1受体(Il1r1)和诱导型一氧化氮合酶(Nos2)在哺乳动物的大脑中. We also showed that IL1RN is an endogenous neuroprotective agent. I was the first to suggest that the central and peripheral cytokine compartments are integrated, 但是有不同的监管. In collaboration with colleagues at Columbia University, we showed that inflammation-mediated up-regulation of secretory sphingomyelin phosphodiesterase represents a link between inflammatory cytokines and atherogenesis. We have recently focused on the role of the inflammasome in the microbiome-gut-brain axis, shedding new light on the bi-directional pathway that links gut microbiota, the inflammasome, 以及类似抑郁的行为.
- We have a line of endocrine research that has a special focus on the biology of human leptin. We discovered that despite being produced by a dispersed mass of fat cells, leptin is secreted in an organized manner with distinct pulsatility and circadian rhythm and that it appears to regulate the minute-to-minute rhythms of several endocrine axes, 比如下丘脑-垂体-肾上腺轴, 下丘脑-垂体-甲状腺轴, 下丘脑-垂体-性腺轴. We were the first to suggest that leptin may have antidepressant effects. We also advanced the concept that leptin has pro-cognitive effects in humans.