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		Search Text: Home/< Back ToThe Science/Translational Research
  Translational Research
    The Laboratory of Translational Research, led by Dr. Joel Moss, focuses on clinical and translational areas of investigation.
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          Joel Moss
  Joel Moss, M.D., Ph.D.
          Senior Investigator
          Email
      Meet the Team
            Contact us
  Senior Investigator Research Interests
            
  Research Interests
              Dr. Moss’s basic research focuses on the post-translational modification of proteins and other molecules by ADP-ribosylation in health and disease. His clinical work focuses on the pathogenesis of cystic lung diseases, such as lymphangioleiomyomatosis (LAM).

Early in his career, Dr. Moss and collaborators discovered that the bacterial toxin, cholera toxin, exerted its effects on mammalian cells by ADP-ribosylation, the transfer of an ADP-ribose group from NAD to an acceptor molecule. He later discovered that mammalian cells contain endogenous enzymes with activities that mimic the ADP-ribosyltransferase (ART) activity of cholera toxin. Subsequently, in trying to determine why the ADP-ribosyltransferase activities of mammalian cells are not toxic, Dr. Moss identified ADP-ribosylarginine hydrolases (ARHs), enzymes that release the ADP-ribose moiety from its acceptor. Exquisite control by ARTs and ARHs makes physiological ADP-ribosylation an effective cellular regulatory mechanism with diverse functions.

Dysregulation of ADP-ribosylation is, conversely, a hallmark of disease. Dr. Moss and colleagues demonstrated that ADP-ribosylation neutralizes the activity of defensin HNP-1, a key effector of the innate immune system that is secreted by neutrophils to kill microorganisms. ADP-ribosylated HNP-1 was identified in the airways of patients with pulmonary disease (e.g. asthma, pulmonary fibrosis) but not in healthy individuals. Further, ADP-ribosylation of arginine was shown to result in the irreversible, non-enzymatic conversion of the arginine to ornithine, a non-coded amino acid. In cholera, the toxin-generated level of intestinal cyclic AMP system activation is significantly greater than normally observed. Dr. Moss and his colleagues showed that in mice lacking the opposing ARH, ARH1, the effects of cholera toxin were demonstrably amplified. More recently, Dr. Moss’s laboratory has shown that mice lacking ARH1 spontaneously develop multiple tumor types, indicating a role for ADP-ribosylation in cancer. Dr. Moss and colleagues subsequently showed that other ARH enzymes (e.g., ARH3) participate in the responses of cells to oxidative stress. He and his team are studying multiple mouse models of disease involving ADP- ribosylation-related genetic knockouts to further elucidate the role of these genes in health and disease.

Given an opportunity to begin a clinical program in parallel with his basic research, Dr. Moss chose to focus on LAM, a disorder characterized by the slow cystic destruction of the lung, affecting primarily women of reproductive age. LAM results from the proliferation of abnormal smooth muscle-like cells and occurs with elevated frequency among women with Tuberous Sclerosis Complex (TSC), an autosomal-dominant syndrome caused by mutations in the TSC1 or TSC2 gene. Dr. Moss and his colleagues initially established the natural history of LAM and the molecular and cellular phenotypes of the LAM cell, the cell responsible for the destruction of the lung parenchyma. Dr. Moss and colleagues took part in a multicenter study showing that sirolimus, an inhibitor of the mechanistic Target of Rapamycin (mTOR), could stabilize lung function. They went on to report that sirolimus therapy resulted in the resolution of the lymphatic manifestations of LAM.

Dr. Moss and his colleagues have extended their study of LAM to include other destructive lung diseases, such as other rare diseases, e.g., pulmonary Langerhans cell histiocytosis, Burt-Hogg-Dube, and common diseases, e.g., COPD
  Clinical Trials and Studies
Study of the Disease Process of Lymphangioleiomyomatosis
				Recruiting
											
											All Ages
					
											All Genders
					
																		Not Accepting Healthy Volunteers

				Have you been diagnosed with LAM? This study is trying to understand the genes and proteins that are responsible for causing lung damage in patients with LAM. To participate in this study, you must be between 16 and 99 years old and diagnosed with LAM. This study is located in Bethesda, Maryland.Nebulized or Inhaled Albuterol for Lymphangioleiomyomatosis
				Recruiting
											
											Adult, Older Adult
					
											Female
					
																		Not Accepting Healthy Volunteers

				Are you an adult female who has been diagnosed with LAM? This study is examining which delivery method of albuterol—inhaled or nebulizer—is better at improving lung function in adult women who have LAM. This study is located in Bethesda, Maryland.Role of Genetic Factors in the Development of Lung Disease
				Recruiting
											
											All Ages
					
											All Genders
					
																		Accepting Healthy Volunteers

				Do you or your child have a lung disease? This study will investigate the genes involved in the breathing process and in the development of lung diseases such as asthma or sarcoidosis to improve understanding of the role they play. To participate in this study, you or your child must be between 2 and 90 years old. This study is located in Bethesda, Maryland, at the NIH Clinical Center.Cutaneous Tumorigenesis in Patients with Tuberous Sclerosis
				Recruiting
											
											Adult, Older Adult
					
											All Genders
					
																		Not Accepting Healthy Volunteers

				Do you have tuberous sclerosis and want to help researchers better understand the disease? This study is investigating what causes multiple skin tumors to develop in people with tuberous sclerosis. To participate in the study, you must be at least 18 years old. This study is located at the NIH Clinical Center in Bethesda, Maryland.Discovery of Sirolimus Sensitive Biomarkers in Blood
				Recruiting
											
											Adult, Older Adult
					
											Female
					
																		Not Accepting Healthy Volunteers

				Do you have LAM and would be willing to help research? This study aims to identify the right dose of sirolimus to treat people who have LAM. To participate in this study, you must be female, between 18 and 90 years old, and diagnosed with LAM. This study is located in Bethesda, Maryland.
Featured Publications
                Effect of beta-agonists on LAM progression and treatment.
            Authors:Le K, Steagall WK, Stylianou M, Pacheco-Rodriguez G, Darling TN, Vaughan M, Moss J.
                                                                                                                        
            Proc Natl Acad Sci U S A.
      
                2018 Jan 30;115(5):E944-E953
        Read Publication
                      Use of CT Imaging to Quantify Progression and Response to Treatment in Lymphangioleiomyomatosis.
            Authors:Gopalakrishnan V, Yao J, Steagall WK, Avila NA, Taveira-DaSilva AM, Stylianou M, Chen MY, Moss J.
                                                                                                                        
            Chest.
      
                2019 May 01;155(5):962-971
        Read Publication
                      Rates of change in FEV1 and DLCO as potential indicators for mTOR inhibitor therapy in premenopausal lymphangioleiomyomatosis patients.
            Authors:Taveira-DaSilva AM, Julien-Williams P, Jones AM, Stylianou M, Moss J.
                                                                                                                        
            Eur Respir J.
      
                2018 Apr 19;51(4):1702258
        Read Publication
                      PARP1 inhibition alleviates injury in ARH3-deficient mice and human cells.
            Authors:Mashimo M, Bu X, Aoyama K, Kato J, Ishiwata-Endo H, Stevens LA, Kasamatsu A, Wolfe LA, Toro C, Adams D, Markello T, Gahl WA, Moss J.
                                                                                                                        
            JCI Insight.
      
                2019 Feb 21;4(4):e124519
        Read Publication
                      Role of a TRIM72 ADP-ribosylation cycle in myocardial injury and membrane repair.
            Authors:Ishiwata-Endo H, Kato J, Tonouchi A, Chung YW, Sun J, Stevens LA, Zhu J, Aponte AM, Springer DA, San H, Takeda K, Yu ZX, Hoffmann V, Murphy E, Moss J
                                                                                                                        
            JCI Insight
      
                2018 Nov 15;3(22):
        Read Publication
                                View More Publications
  Meet the Team

    Joel Moss

            Joel Moss, M.D., Ph.D.
                Senior Investigator
                Joel Moss graduated summa cum laude from Brandeis University in 1966 with a B.A. in chemistry and earned his M.D. and Ph.D. degrees from New York University School of Medicine in 1972. Following internship and residency at Johns Hopkins Hospital, Dr. Moss joined the NHLBI in 1974 as a research associate and pulmonary fellow. Since 2007, he has been head of the Translational Research Section and of the Lymphangioleiomyomatosis (LAM) Research Program. Dr. Moss has received multiple awards, including LAM Foundation Award (1999 and 2010), and the New York University Alumni Achievement Award in Basic Science in 2009. Dr. Moss is an honorary member of the Peruvian Thoracic Society and received the Chiba (Japan) Medical Society Award. He is also a member of American Society for Clinical Investigation for which he was a Councillor and Vice-President. In 2009, Dr. Moss was elected to the Johns Hopkins University Society of Scholars. He is a Fellow of the American College of Chest Physicians. Dr. Moss has authored or coauthored more than 630 papers, edited and co-authored several books and is a co-inventor of several patents. Dr. Moss has been an editor of the Journal of Biological Chemistry and the Journal of Clinical Investigation. He is currently an Editor of the American Journal of Respiratory Cell and Molecular Biology and is a designated Associate Editor of CHEST through 2015.

NHLBI Orloff Award 2016: Dr. Joel Moss
    
          Contact the lab
    10 Center DrBethesda, MD 20892United States
        Phone:
                    301-496-1597
                Fax:
            301-496-2363
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            Pauline Barnes, R.N.
        

    Scientific Support Staff

        barnespm@mail.nih.gov
            Linda Stevens
    
            Linda Stevens
        

    Scientific Support Staff

        stevensl@nhlbi.nih.gov
            Mary Haughey
    
            Mary Haughey, R.N.
        

    Research Nurse

        mh325z@nih.gov
            Angelo Taviera Dasilva
    
            Angelo Taveira Dasilva, M.D., Ph.D.
        

    Staff Clinician

        dasilvaa@nhlbi.nih.gov
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            Hai Ping Wu
        

    Scientific Support Staff

        wuhp@nhlbi.nih.gov
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            Ivan Rosas, M.D.
        

    Special Volunteer

        ivan.rosas@nih.gov
            Wendy Steagall
    
            Wendy Steagall, Ph.D.
        

    Scientific Support Staff

        steagalw@nhlbi.nih.gov
            Jiro Kato
    
            Jiro Kato, D.D.S, M.D.
        

    Staff Scientist

        jk256k@nih.gov
            Gustavo Pacheco
    
            Gustavo Pacheco, Ph.D.
        

    Staff Scientist

        gp64v@nih.gov
            Hiroko Endo
    
            Hiroko Endo, Ph.D.
        

    Postdoctoral Fellow

        endohiro@mail.nih.gov
            Xiangning Bu
    
            Xiangning Bu, Ph.D.
        

    Postdoctoral Fellow

        xiangning.bu@nih.gov
            Amanda Jones
    
            Amanda Jones, R.N.
        

    Nurse Practitioner

        jonesam@mail.nih.gov
            Li Zhang
    
            Li Zhang, Ph.D.
        

    Postdoctoral Fellow

        zhangl12@mail.nih.gov
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            Patricia Julien-Williams
        

    Nurse Practitioner

        williamspa@mail.nih.gov
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