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		Search Text: Home/< Back ToThe Science/Obesity and Metabolic Diseases
  Obesity and Metabolic Diseases
    The broad interest of the Laboratory of Obesity and Metabolic Diseases, led by Dr. Haiming Cao, is to understand the complex regulation of energy metabolism and uncover its significance in the pathogenesis of metabolic disease.
    On This Page
    
          Haiming Cao
  Haiming Cao, Ph.D.
          Senior Investigator
          Email
      Meet the Team
            Contact us
  Senior Investigator Research Interests
            
  Research Interests
              The broad interest of the Cao group is to understand the complex regulation of energy metabolism and uncover its significance in the pathophysiology of metabolic disease. The worldwide obesity epidemic—along with an array of obesity-related disorders, particularly diabetes, fatty liver and cardiovascular diseases—has become a major public health threat in the 21st century. The molecular and pathological basis by which obesity induces metabolic disorders, however, remains incompletely understood, hampering the development of effective therapies against these debilitating diseases.Our current knowledge of energy metabolism is mostly based on studies of protein coding genes, which constitute less than 2% of the human genome. Although the remainder of the genome was initially considered to consist predominantly of gene deserts, thorough examinations of the mammalian transcriptomes in recent years have uncovered tens of thousands of long noncoding RNAs (lncRNAs). In humans, lncRNAs are at least three times more prevalent than protein-coding genes but their physiological function is largely unknown. The Cao group has recently demonstrated that a number of long noncoding RNAs could function as vital metabolic regulators in mice (Cell Metabolism, March 2015, Cell Reports, March 2016 and Cell Metabolism, October 2016). These findings also suggest that energy metabolism-associated lncRNAs may have systemic regulatory effects, and that the dysregulation of these lncRNAs could be the underlying cause for many metabolic abnormalities.If human lncRNAs play a similar role as their rodent counterparts, understanding their physiological significance could rapidly enhance our understanding of human metabolism and substantially increase the number of potential therapeutic targets for metabolic diseases. However, most human lncRNAs are human- or primate-specific, vastly limiting our ability to identify and experimentally define human lncRNAs that regulate metabolism. To address these intriguing and challenging questions, **the Cao group has recently developed two extensive pipelines leveraging the information of genome-wide association studies (Nature Communications, 2020) and clinical studies of metabolic disorders (Journal of Clinical Investigation, 2020) for the identification of human lncRNA metabolic regulators.** Furthermore, we have also identified micropeptides derived from putative human lncRNAs that play a critical role in nutrient sensing and glucose metabolism. To define the metabolic function of human-specific lncRNAs in a physiologically relevant setting, we have recently produced humanized mice in which over 90% of the mouse liver cells are replaced by human hepatocytes, or essentially mice carrying a human liver. Using these powerful pipelines and humanized murine model, the lab has recently demonstrated that multiple human-specific lncRNAs regulate critical signaling networks in human metabolism. The significance of these lncRNAs in human disease is currently being corroborated by studying their functions in samples from patients who suffer from a range of metabolic disorders.Videos

        
  
Haiming Cao, PhD, and his team won the Orloff Award for demonstrating the vital role of long noncoding RNA in metabolism and for developing a novel approach to study long noncoding RNA’s function in metabolic diseases. Watch Dr. Cao explain long noncoding RNA and his team’s work.
  Images






          disease mutation
      
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    Disease-causing mutation


        
            From our lab: Disease-causing mutation.


                      iPS cells from our mice
      
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    iPS cells from our mice


        
            Mice iPS cells


                      iPS cells from our patients
      
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    iPS cells from our patients


        
            Patient iPS cells


                      fat lab mouse
      
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    Our fat mouse


        
            Mice from our lab


                      individual fat cell
      
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    Our fat cell (individual)


        
            Individual fat cells


                      cluster of fat cells
      
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    Our fat cells (cluster)


        
            A cluster of fat cells


                      view of lab
      
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    View of our lab


        
            One view of our lab


                      secondary view of lab
      
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    Another view of our lab


        
            Secondary view of the lab


                      lab cell culture room
      
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    Our cell culture room


        
            The cell culture room of our lab


                      nhlbi lab building
      
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    Lab building from afar


        
            The lab building is located at the NIH campus in Bethesda, MD.
      disease mutation


                      
iPS cells from our mice


                      
iPS cells from our patients


                      
fat lab mouse


                      
individual fat cell


                      
cluster of fat cells


                      
view of lab


                      
secondary view of lab


                      
lab cell culture room


                      
nhlbi lab building
Featured Publications
                Identification of human long non-coding RNAs associated with nonalcoholic fatty liver disease and metabolic homeostasis.
            Authors:Ruan X, Li P, Ma Y, Jiang C, Chen Y, Shi Y, Gupta N, Seifuddin F, Pirooznia M, Ohnishi Y, Yoneda N, Nishiwaki M, Dumbovic G, Rinn JL, Higuchi Y, Kawai K, Suemizu H, Cao H.
                                                                
            J Clin Invest.
      
                2020 Oct 13:136336
        Read Publication
                      In vivo functional analysis of non-conserved human lncRNAs associated with cardiometabolic traits.
            Authors:Ruan X, Li P, Chen Y, Shi Y, Pirooznia M, Seifuddin F, Suemizu H, Ohnishi Y, Yoneda N, Nishiwaki M, Shepherdson J, Suresh A, Singh K, Ma Y, Jiang CF, Cao H.
                                                                                                                        
            Nat Commun. 
      
                2020 Jan 02;11(1):45
        Read Publication
                      Integrative Transcriptome Analyses of Metabolic Responses in Mice Define Pivotal LncRNA Metabolic Regulators.
            Authors:Yang L, Li P, Yang W, Ruan X, Kiesewetter K, Zhu J, Cao H
                                                                                                                        
            Cell Metab
      
                2016 Oct 11;24(4):627-639
        Read Publication
                      A Long Non-coding RNA, lncLGR, Regulates Hepatic Glucokinase Expression and Glycogen Storage during Fasting.
            Authors:Ruan X, Li P, Cangelosi A, Yang L, Cao H
                                                                                                                        
            Cell Rep.
      
                2016 Feb 16;S2211-1247(16):30040-7
        Read Publication
                      A Liver-Enriched Long Non-Coding RNA, lncLSTR, Regulates Systemic Lipid Metabolism in Mice.
            Authors:Li P, Ruan X, Yang L, Kiesewetter K, Zhao Y, Luo H, Chen Y, Gucek M, Zhu J, Cao H
                                                                                                                        
            Cell Metab
      
                2015 Mar 03;21(3):455-67
        Read Publication
  Meet the Team

    Haiming Cao

            Haiming Cao, Ph.D.
                Senior Investigator
                Haiming Cao earned his Ph.D. in biochemistry in 2003 from the University of Nevada Reno. He did his postdoctoral training at Harvard University from 2003 to 2010. Dr. Cao joined the NHLBI as an Earl Stadtman Investigator in 2011.
    
          Contact the lab
    10 Center DrBethesda, MD 20814United States
        Phone:
                    301-402-9032
                Fax:
  Yonghe Ma
    
            Yonghe Ma, Ph.D.
        

    Postdoctoral Fellow
            Cheng-fei
    
            Cheng-fei Jiang, Ph.D.
        

    Postdoctoral Fellow
            Kaiyuan Wu, PhD
    
            Kaiyuan Wu, Ph.D.
        

    Staff Scientist
            Zhe Li
    
            Zhe Li
        

    Postdoctoral Fellow

        zhe.li3@nih.gov
            Sunmi Seok, PhD
    
            Sunmi Seok, Ph.D.
        

    Staff Scientist

        sunmi.seok@nih.gov
            Hang Sun
        

    Postbaccalaureate Fellow

        hang.sun@nih.gov Back To Top Link
  

        

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