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Research

The NIAAA is the lead agency for U.S. research on the causes, consequences, prevention and treatment of alcohol use disorder and alcohol-related problems.

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Section on Clinical Genomics and Experimental Therapeutics (CGET)

Contact Information

  • Office: 301-827-1542

Overview of the Lab

What we do

The Section on Clinical Genomics and Experimental Therapeutics (CGET) conducts pre-clinical studies and translational clinical studies with focus on genomics and epigenetics related to the pathophysiology and treatment of alcohol use disorders and addictions. The pre-clinical work focuses on identifying molecular mechanisms involved in addictions, utilizing a wide array of methods including human population genetics, genome wide genotyping approaches, next-generation DNA and RNA sequencing and epigenetic/proteomic profiling. Findings are translated into human clinical studies using molecular biomarker, pharmacogenetic, epigenetic and functional imaging genetic approaches. Clinical studies include early phase 1 / phase 2 proof-of-concept studies of experimental novel therapeutics guided by molecular biomarker profiling. One current phase 1 study aims to characterize safety, tolerability and bioeffects of a PCSK9 inhibitor called alirocumab in non-treatment seeking heavy drinkers. This study will focus on potential therapeutic effects for liver related endpoints and explores bioeffects of alirocumab with regards to potential biomarkers.

Current Protocol

000036-AA: Safety, Tolerability and Bioeffects of Alirocumab in Non-Treatment Seeking Heavy Drinkers 

This research study will evaluate the safety and efficacy of the drug alirocumab on liver enzymes and liver damage in heavy drinkers.

Research participation includes 7 outpatient visits over 8 weeks. Most study visits consist of blood draws, clinical assessments, and administration of the drug (or placebo) and last approximately 2 hours. The first and last study visits include optional liver MRI, FibroScan, and doppler/ultrasound assessments and last about 4-5 hours.

The study is enrolling 21–65-year-old male and female heavy drinkers (more than 20 drinks/week). You may not be eligible if you are pregnant or breastfeeding, are currently seeking treatment for alcohol-related problems, or if you have certain serious medical conditions. 

The study is conducted at the NIH Clinical Center in Bethesda, MD. There is no cost to participate and compensation up to $2640 may be provided.

To find out if you qualify, email NIAAACGETResearch@mail.nih.gov.

ClinicalTrials.gov Identifier: NCT04781322

Research Projects

 

  • Epigenetics and addiction
  • Genetics and addiction 
  • PCSK9 and alcohol use disorder
  • Aging and alcohol use

Lab Members

Selected Publications

Search Pubmed for articles by Dr. Lohoff

  1. Mendelian Randomization Study of PCSK9 and HMG-CoA Reductase Inhibition and Cognitive Function.
    Rosoff DB, Bell AS, Jung J, Wagner J, Mavromatis LA, Lohoff FW.
    J Am Coll Cardiol. 2022 Aug 16;80(7):653-662. doi: 10.1016/j.jacc.2022.05.041.
    PMID: 35953131
  2. Association Between Brain Structure and Alcohol Use Behaviors in Adults: A Mendelian Randomization and Multiomics Study.
    Mavromatis LA, Rosoff DB, Cupertino RB, Garavan H, Mackey S, Lohoff FW.
    JAMA Psychiatry. 2022 Sep 1;79(9):869-878. doi: 10.1001/jamapsychiatry.2022.2196.
    PMID: 35947372 Free PMC article.
  3. Alcohol use disorder is associated with DNA methylation-based shortening of telomere length and regulated by TESPA1: implications for aging.
    Jung J, McCartney DL, Wagner J, Rosoff DB, Schwandt M, Sun H, Wiers CE, de Carvalho LM, Volkow ND, Walker RM, Campbell A, Porteous DJ, McIntosh AM, Marioni RE, Horvath S, Evans KL, Lohoff FW.
    Mol Psychiatry. 2022 Jun 15. doi: 10.1038/s41380-022-01624-5. Online ahead of print.
    PMID: 35705636
  4. Targeting Unmet Clinical Needs in the Treatment of Alcohol Use Disorder.
    Lohoff FW.
    Front Psychiatry. 2022 Jun 9;13:767506. doi: 10.3389/fpsyt.2022.767506. eCollection 2022.
    PMID: 35757224Free PMC article.Review.
  5. Epigenome-wide association study of alcohol consumption in N = 8161 individuals and relevance to alcohol use disorder pathophysiology: identification of the cystine/glutamate transporter SLC7A11 as a top target.
    Lohoff FW, Clarke TK, Kaminsky ZA, Walker RM, Bermingham ML, Jung J, Morris SW, Rosoff D, Campbell A, Barbu M, Charlet K, Adams M, Lee J, Howard DM, O'Connell EM, Whalley H, Porteous DJ, McIntosh AM, Evans KL.
    Mol Psychiatry. 2022 Mar;27(3):1754-1764. doi: 10.1038/s41380-021-01378-6. Epub 2021 Dec 2.
    PMID: 34857913 Free PMC article.
  6. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in the Brain and Relevance for Neuropsychiatric Disorders.
    O'Connell EM, Lohoff FW.
    Front Neurosci. 2020 Jun 12;14:609. doi: 10.3389/fnins.2020.00609. eCollection 2020.
    PMID: 32595449Free PMC article.Review.
  7. Epigenome-wide association study and multi-tissue replication of individuals with alcohol use disorder: evidence for abnormal glucocorticoid signaling pathway gene regulation.
    Lohoff FW, Roy A, Jung J, Longley M, Rosoff DB, Luo A, O'Connell E, Sorcher JL, Sun H, Schwandt M, Hodgkinson CA, Goldman D, Momenan R, McIntosh AM, Adams MJ, Walker RM, Evans KL, Porteous D, Smith AK, Lee J, Muench C, Charlet K, Clarke TK, Kaminsky ZA.
    Mol Psychiatry. 2021 Jun;26(6):2224-2237. doi: 10.1038/s41380-020-0734-4. Epub 2020 May 12.
    PMID: 32398718 Free PMC article.
  8. PCSK9 inhibition as a novel therapeutic target for alcoholic liver disease.
    Lee JS, Mukhopadhyay P, Matyas C, Trojnar E, Paloczi J, Yang YR, Blank BA, Savage C, Sorokin AV, Mehta NN, Vendruscolo JCM, Koob GF, Vendruscolo LF, Pacher P, Lohoff FW.
    Sci Rep. 2019 Nov 20;9(1):17167. doi: 10.1038/s41598-019-53603-6.
    PMID: 31748600 Free PMC article.
  9. DNA methylation age is accelerated in alcohol dependence.
    Rosen AD, Robertson KD, Hlady RA, Muench C, Lee J, Philibert R, Horvath S, Kaminsky ZA, Lohoff FW.
    Transl Psychiatry. 2018 Sep 5;8(1):182. doi: 10.1038/s41398-018-0233-4.
    PMID: 30185790 Free PMC article.
  10. Methylomic profiling and replication implicates deregulation of PCSK9 in alcohol use disorder.
    Lohoff FW, Sorcher JL, Rosen AD, Mauro KL, Fanelli RR, Momenan R, Hodgkinson CA, Vendruscolo LF, Koob GF, Schwandt M, George DT, Jones IS, Holmes A, Zhou Z, Xu MJ, Gao B, Sun H, Phillips MJ, Muench C, Kaminsky ZA.
    Mol Psychiatry. 2018 Sep;23(9):1900-1910. doi: 10.1038/mp.2017.168. Epub 2017 Aug 29.
    PMID: 28848234 Free PMC article.

Other Lab Resources

Past CGET Members

Name
Undergraduate Institution
Time with CGET
Current Position
Current Institution

Emma O'Connell, B.S.

Georgetown University

Post-Baccalaureate IRTA Fellow

2019-2021

Ph.D.

Stanford University,

Stanford, CA

Martha Longley, B.S.

Yale University

Post-Baccalaureate IRTA Fellow

2018-2020

M.D./Ph.D.

Harvard University,

Cambridge, MA

Katrin Charlet, Ph.D.

Charité - Universitätsmedizin Berlin, Germany

Post-Doctoral Visiting Fellow

2017-2020

 

Christine Muench, Ph.D.

Bielefeld University & American University

Post-Doctoral Fellow

2015-2020

Medical Scientific Liason in Psychiatry,

The Janssen Pharmaceutical Companies of

Johnson & Johnson

Audrey Luo, B.S.

Yale University

Post-Baccalaureate IRTA Fellow

2017-2019

 

M.D./Ph.D.

University of Pennsylvania,

Philadelphia, PA

Kelsey Mauro, B.A.

George Washington University

Post-Baccalaureate IRTA Fellow

2016-2018

 

Ph.D., Clinical Psychology

George Mason University

Fairfax, VA

 

Jill Sorcher, B.A.

University of Pennsylvania

Post-Baccalaureate IRTA Fellow

2016-2017

 

Medical School

John Hopkins University School of Medicine

Baltimore, MD

Alison Rosen, B.S.

Brown University

Post-Baccalaureate IRTA Fellow

2015-2017

 

Ph.D., Epidemiology

University of California, Los Angeles

Los Angeles, CA

Elizabeth Tawa, B.S.

Swarthmore College

Post-Baccalaureate IRTA Fellow

2015-2016

 

Ph.D., Neuroscience

Princeton University

Princeton, NJ

Sarah Grace Helton, B.A.

Vanderbilt University

Post-Baccalaureate IRTA Fellow

2014-2016

 

Ph.D., Clinical Psychology

Rutgers University

New Brunswick, NJ

Rebecca R. Fanelli, Ph.D.

Post-Doctoral Fellow

2015-2016

 

Senior Country Approval Specialist,

PPD

Morrisville, NC

Sam Hall, B.S.

University of Wisconsin-Madison

Post-Baccalaureate IRTA Fellow

2013-2015

 

Medical School

Medical College of Wisconsin

Milwaukee, WI

Nisha Dutta, B.S.

Duke University

Post-Baccalaureate IRTA Fellow

2014-2015

 

Business Associate/Healthcare Consulting

ZS Associates, Inc

San Francisco/Silicon Valley, CA

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