Skip to main content
NIH Intramural Research Program, Our Research Changes Lives

Navigation controls

  • Search
  • Menu

Social follow links

  • Podcast
  • Instagram
  • Twitter
  • YouTube
  • LinkedIn

Main navigation

  • About Us
    • What Is the IRP?
    • History
    • Honors
      • Nobel Prize
      • Lasker Award
      • Breakthrough Prize
      • Shaw Prize
      • Presidential Early Career Award for Scientists and Engineers (PECASE)
      • Presidential Medal of Freedom
      • National Medal of Science
      • Searle Scholars
      • The National Academy of Sciences
      • The National Academy of Medicine
      • The National Academy of Engineering
      • The American Academy of Arts and Sciences
      • National Medal of Technology & Innovation
      • Samuel J. Heyman Service to America Medals
      • Crafoord Prize
      • Fellows of the Royal Society
      • Canada Gairdner Awards
    • Organization & Leadership
    • Our Programs
      • NCI
      • NEI
      • NHGRI
      • NHLBI
      • NIA
      • NIAAA
      • NIAID
      • NIAMS
      • NIBIB
      • NICHD
      • NIDA
      • NIDCD
      • NIDCR
      • NIDDK
      • NIEHS
      • NIMH
      • NIMHD
      • NINDS
      • NINR
      • NLM
      • CC
      • NCATS
      • NCCIH
    • Research Campus Locations
    • Contact Information
  • Our Research
    • Scientific Focus Areas
      • Biomedical Engineering & Biophysics
      • Cancer Biology
      • Cell Biology
      • Chemical Biology
      • Chromosome Biology
      • Clinical Research
      • Computational Biology
      • Developmental Biology
      • Epidemiology
      • Genetics & Genomics
      • Health Disparities
      • Immunology
      • Microbiology & Infectious Diseases
      • Molecular Biology & Biochemistry
      • Molecular Pharmacology
      • Neuroscience
      • RNA Biology
      • Social & Behavioral Sciences
      • Stem Cell Biology
      • Structural Biology
      • Systems Biology
      • Virology
    • Principal Investigators
      • View by Investigator Name
      • View by Scientific Focus Area
    • Accomplishments
      • View All Accomplishments by Date
      • View All Health Topics
      • The Body
      • Health & Wellness
      • Conditions & Diseases
      • Procedures
    • Accelerating Science
      • Investing in Cutting-Edge Animal Models
      • Creating Cell-Based Therapies
      • Advancing Computational and Structural Biology
      • Combating Drug Resistance
      • Developing Novel Imaging Techniques
      • Charting the Pathways of Inflammation
      • Zooming in on the Microbiome
      • Uncovering New Opportunities for Natural Products
      • Stimulating Neuroscience Research
      • Pursuing Precision Medicine
      • Unlocking the Potential of RNA Biology and Therapeutics
      • Producing Novel Vaccines
    • Research in Action
      • View All Stories
      • Battling Blood-Sucking Bugs
      • Unexpected Leads to Curb Addiction
      • Shaping Therapies for Sickle Cell Disease
      • The Mind’s Map Maker
    • Trans-IRP Research Resources
      • Supercomputing
    • IRP Review Process
    • Commercializing Inventions
  • NIH Clinical Center
    • Clinical Center Facilities
    • Clinical Faculty
    • Advancing Translational Science
    • Clinical Trials
      • Get Involved with Clinical Research
      • Physician Resources
  • News & Events
    • In the News
    • I am Intramural Blog
    • Speaking of Science Podcast
    • SciBites Video Shorts
    • The NIH Catalyst Newsletter
    • Events
  • Careers
    • Faculty-Level Scientific Careers
    • Trans-NIH Scientific Recruitments
      • Stadtman Tenure-Track Investigators
        • Science, the Stadtman Way
      • Lasker Clinical Research Scholars
      • Independent Research Scholar
    • Scientific & Clinical Careers
    • Administrative Careers
  • Research Training
    • Program Information
    • Training Opportunities
    • NIH Work/Life Resources
The NIH Catalyst: A Publication About NIH Intramural Research

National Institutes of Health • Office of the Director | Volume 21 Issue 3 • May–June 2013

Research Briefs

NIDA: RESETTING THE ADDICTED BRAIN

Could drug addiction treatment of the future be as simple as an on-off switch in the brain? A study in rats has found that stimulating a key part of the brain reduces compulsive cocaine-seeking behavior and suggests the possibility of changing addictive behavior generally. NIDA researchers used an animal model of cocaine addiction in which some rats exhibited addictive behavior by pushing levers to get cocaine even when followed by a mild electric shock to the foot. Other rats did not exhibit addictive responses.

The NIDA scientists compared nerve-cell firing patterns in both groups of rats by examining cells from the prefrontal cortex. They determined that cocaine produced greater functional brain deficits in the addicted rats. The researchers then used optogenetic techniques on both groups of rats—essentially, shining a light onto modified cells to increase or lessen activity in that part of the brain. In the addicted rats, activating the brain cells (thereby removing the deficits) reduced cocaine-seeking behavior. In the nonaddicted rats, deactivating the brain cells (thereby creating the deficits) increased compulsive cocaine seeking.

This is the first study to show a cause-and-effect relationship between cocaine-induced brain deficits in the prefrontal cortex and compulsive cocaine seeking. The results provide evidence for a cocaine-induced deficit within a brain region that is involved in disorders characterized by poor impulse control, including addiction. The researchers hope that the findings can lead to treatments that would reduce compulsive cocaine seeking and craving in patients. (NIH authors: B.T. Chen, H.-J. Yau, C. Hatch, I. Kusumoto-Yoshida, A. Bonci; Nature 496:359–362, 2013)


NICHD, NINDS, NCI: NEW SYNDROME LINKED TO A SOMATIC HIF2A MUTATION

A team of NIH researchers, in collaboration with scientists from the University of Utah (Salt Lake City) and Tufts Medical Center (Boston), have identified a new syndrome involving two rare neuroendocrine tumors and a rare blood disease. The syndrome was observed in four female patients who had multiple paraganglioma and somatostatinoma tumors and the blood disease polycythemia.

Somatic mutations in the gene that encodes hypoxia-inducible factor–2-alpha (HIF2A) cause increased production of erythropoietin, which leads to increased red blood cell production called polycythemia. The mutations increase HIF2A stability and enhance its functional capacity by extending its half-life.

images of patient with multiple tumors

Courtesy of K. Pacak, NICHD

Functional and anatomic imaging; (A, B) 18F-fluorodopa positron emission tomography (PET)/computed tomography (CT) showing multiple tumors in a patient; (C, D) Early arterial phase of axial CT of abdomen performed with negative enteric contrast showing small masses in another patient.

Symptoms of the new syndrome include high blood pressure, heart palpitations, headaches, and anxiety. Polycythemia in the four women was found either at birth or in early childhood. All developed tumors later in life (the paragangliomas were in the abdomen and somatostatinomas in the duodenum). It is not clear whether the syndrome also exists in men.

Increasing HIF expression has been shown in many tumors, but HIF mutations have never been reported in tumors. The research is the first to provide direct evidence of HIF involvement in tumorigenesis and suggests that inhibiting HIF2A may be a way to treat the disease. The team is currently exploring that avenue. (NICHD authors: K. Pacak, I. Jochmanova, T. Prodanov; NCI authors: M. Merino, T. Fojo; NINDS authors: Z. Zhuang, C. Yang; J Clin Oncol 31:1690–1698 2013)


NIEHS: DISCOVERY OF GENE THAT IS MUTATED IN NEURODEGENERATIVE DISEASE

An international research team that included several NIEHS scientists has identified a novel factor that removes poly[adenosine diphosphate (ADP)–ribose] chains from proteins. Originally called C6orf130, the scientists renamed this gene TARG1 and its protein terminal ADP-ribose protein glycohydrolase (TARG1) because it cuts off ADP-ribose and poly(ADP-ribose) units that are directly attached to proteins. Individuals who inherit two defective copies of the TARG1 gene suffer from a progressive neurodegenerative disease characterized by seizures, lack of tendon reflex, and a weakened swallowing reflex.

The tagging of ADP-ribose chains to proteins controls gene expression, cell death, and cellular responses to DNA damage. Using X-ray crystallography and cell biological and biochemical approaches, the research team demonstrated that TARG1, a member of a large class of macrodomain proteins, homes in on and erases ADP-ribose tags. The work shows that this TARG1 action is critical for cells to coordinate normal DNA repair processes in support of proper cellular function. Future work is required to gain a better understanding of when and where TARG1 acts to regulate cellular functions. (NIEHS authors: C.D. Appel, M.J. Schellenberg, J.G. Williams, J. Krahn, R.S. Williams; EMBO J 32:1225–1237, 2013)


NIDDK: ACTIVITATING THE BETA CELL PATHWAY TO PROTECT AGAINST DIABETES

islet cells

SHALINIL JAIN, NIDDK

Activation of a novel signaling pathway in beta cells maintains healthy mouse pancreatic islets (brown).

In type 2 diabetes (T2D), pancreatic beta cells fail to release enough insulin to maintain blood glucose concentrations within a normal range. So scientists are trying to develop therapeutic strategies that would improve the function of defective pancreatic beta cells.

NIDDK researchers recently demonstrated that stimulating a specific type of cell-surface receptor activated a novel beta cell–signaling pathway that had multiple metabolic benefits in mice. The mice were protected against experimentally induced diabetes and glucose intolerance that had been provoked by either streptozotocin (a toxin that selectively destroys beta cells) or an energy-rich, high-fat diet. The findings provide a rational basis for the development of anti-diabetic drugs targeting this class of receptors. (NIDDK authors: S. Jain, I. Ruiz de Azua, H. Lu, J.-M. Guettier, J. Wess; J Clin Invest 123:1750-1762, 2013)


Contributors: Bob Bock, NICHD; Robin Arnette, NIEHS; Krysten Carrera, NIDDK

This page was last updated on Thursday, April 28, 2022

  • Issue Overview
  • Features
    • Collaboration Leads to Better Imaging
    • FAES Opens New Academic Center
    • Lin Asks Why: An Interview with NHGRI Scientist Paul Liu
    • Neal Young: Conquering Aplastic Anemia
    • The Perils of Nipah Virus and Ischemic Stroke
  • Departments
    • Announcements
    • Colleagues: Recently Tenured
    • From the Deputy Director for Intramural Research
    • New Methods
    • News You Can Use
    • NIH in History
    • Research Briefs
    • The SIG Beat
    • The Training Page
  • Issue Contents
  • Download this issue as a PDF

Catalyst menu

  • Current Issue
  • Previous Issues
  • About The NIH Catalyst
  • Contact The NIH Catalyst
  • Share Your Story
  • NIH Abbreviations

Subscribe Today!

Subscribe to The NIH Catalyst Newsletter and receive email updates.

Subscribe

Get IRP Updates

Subscribe

  • Email
  • Print
  • Share Twitter Facebook LinkedIn

Main navigation

  • About Us
    • What Is the IRP?
    • History
    • Honors
    • Organization & Leadership
    • Our Programs
    • Research Campus Locations
    • Contact Information
  • Our Research
    • Scientific Focus Areas
    • Principal Investigators
    • Accomplishments
    • Accelerating Science
    • Research in Action
    • Trans-IRP Research Resources
    • IRP Review Process
    • Commercializing Inventions
  • NIH Clinical Center
    • Clinical Center Facilities
    • Clinical Faculty
    • Advancing Translational Science
    • Clinical Trials
  • News & Events
    • In the News
    • I am Intramural Blog
    • Speaking of Science Podcast
    • SciBites Video Shorts
    • The NIH Catalyst Newsletter
    • Events
  • Careers
    • Faculty-Level Scientific Careers
    • Trans-NIH Scientific Recruitments
    • Scientific & Clinical Careers
    • Administrative Careers
  • Research Training
    • Program Information
    • Training Opportunities
    • NIH Work/Life Resources
  • Department of Health and Human Services
  • National Institutes of Health
  • USA.gov

Footer

  • Home
  • Contact Us
  • IRP Brand Materials
  • HHS Vulnerability Disclosure
  • Web Policies & Notices
  • Site Map
  • Search