Section on Clinical Genomics and Experimental Therapeutics (CGET)
Contact Information
- Office: 301-827-1542
-
Mailing Address
Lasker Clinical Research Scholar National Institute on Alcohol Abuse and Alcoholism (NIAAA) National Institutes of Health (NIH)
10 Center Drive (10CRC/2-2352)
Bethesda , MD 20892-1540
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
- 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 - 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. - 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 - 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. - 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. - 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. - 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. - 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. - 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. - 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 |
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Martha Longley, B.S. Yale University Post-Baccalaureate IRTA Fellow 2018-2020 |
M.D./Ph.D. Harvard University, Cambridge, MA |
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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 |
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Audrey Luo, B.S. Yale University Post-Baccalaureate IRTA Fellow 2017-2019
|
M.D./Ph.D. University of Pennsylvania, Philadelphia, PA |
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Kelsey Mauro, B.A. George Washington University Post-Baccalaureate IRTA Fellow 2016-2018
|
Ph.D., Clinical Psychology George Mason University Fairfax, VA
|
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Jill Sorcher, B.A. University of Pennsylvania Post-Baccalaureate IRTA Fellow 2016-2017
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Medical School John Hopkins University School of Medicine Baltimore, MD |
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Alison Rosen, B.S. Brown University Post-Baccalaureate IRTA Fellow 2015-2017
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Ph.D., Epidemiology University of California, Los Angeles Los Angeles, CA |
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Elizabeth Tawa, B.S. Swarthmore College Post-Baccalaureate IRTA Fellow 2015-2016
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Ph.D., Neuroscience Princeton University Princeton, NJ |
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Sarah Grace Helton, B.A. Vanderbilt University Post-Baccalaureate IRTA Fellow 2014-2016
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Ph.D., Clinical Psychology Rutgers University New Brunswick, NJ |
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Rebecca R. Fanelli, Ph.D. Post-Doctoral Fellow 2015-2016
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Senior Country Approval Specialist, PPD Morrisville, NC |
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Sam Hall, B.S. University of Wisconsin-Madison Post-Baccalaureate IRTA Fellow 2013-2015
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Medical School Medical College of Wisconsin Milwaukee, WI |
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Nisha Dutta, B.S. Duke University Post-Baccalaureate IRTA Fellow 2014-2015
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Business Associate/Healthcare Consulting ZS Associates, Inc San Francisco/Silicon Valley, CA |