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 $2430 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. Lee, J. S., P. Mukhopadhyay, C. Matyas, E. Trojnar, J. Paloczi, Y. R. Yang, B. A. Blank, C. Savage, A. V. Sorokin, N. N. Mehta, J. C. M. Vendruscolo, G. F. Koob, L. F. Vendruscolo, P. Pacher and F. W. Lohoff (2019). "PCSK9 inhibition as a novel therapeutic target for alcoholic liver disease." Scientific Reports 9(1): 17167.

  2. Luo, A., J. Jung, M. Longley, D. B. Rosoff, K. Charlet, C. Muench, J. Lee, C. A. Hodgkinson, D. Goldman, S. Horvath, Z. A. Kaminsky and F. W. Lohoff (2020). "Epigenetic aging is accelerated in alcohol use disorder and regulated by genetic variation in APOL2." Neuropsychopharmacology 45(2): 327-336.

  3. Muench, C., K. Charlet, N. L. Balderston, C. Grillon, M. Heilig, C. R. Cortes, R. Momenan and F. W. Lohoff (2019). "Fear conditioning and extinction in alcohol dependence: Evidence for abnormal amygdala reactivity." Addict Biol: e12835.

  4. Rosoff, D. B., T.-K. Clarke, M. J. Adams, A. M. McIntosh, G. Davey Smith, J. Jung and F. W. Lohoff (2019). "Educational attainment impacts drinking behaviors and risk for alcohol dependence: results from a two-sample Mendelian randomization study with ~780,000 participants." Molecular Psychiatry.

  5. Rosen, A. D., K. D. Robertson, R. A. Hlady, C. Muench, J. Lee, R. Philibert, S. Horvath, Z. A. Kaminsky, and F. W. Lohoff. "DNA Methylation Age Is Accelerated in Alcohol Dependence." Transl Psychiatry 8, no. 1 (Sep 5 2018): 182.

  6. Muench, C., M. Schwandt, J. Jung, C. R. Cortes, R. Momenan, and F. W. Lohoff. "The Major Depressive Disorder Gwas-Supported Variant Rs10514299 in Tmem161b-Mef2c Predicts Putamen Activation During Reward Processing in Alcohol Dependence." Transl Psychiatry 8, no. 1 (Jul 13 2018): 131.

  7. Wiers, C. E., F. W. Lohoff, J. Lee, C. Muench, C. Freeman, A. Zehra, S. Marenco, et al. "Methylation of the Dopamine Transporter Gene in Blood Is Associated with Striatal Dopamine Transporter Availability in Adhd: A Preliminary Study." Eur J Neurosci 48, no. 3 (Aug 2018): 1884-95.

  8. Muench, C., C. E. Wiers, C. R. Cortes, R. Momenan, and F. W. Lohoff. "Dopamine Transporter Gene Methylation Is Associated with Nucleus Accumbens Activation During Reward Processing in Healthy but Not Alcohol-Dependent Individuals." Alcohol Clin Exp Res 42, no. 1 (Jan 2018): 21-31.

  9. Genetic Variation in the Vesicular Monoamine Transporter 1 (VMAT1/SLC18A1) Gene and Alcohol Withdrawal Severity. Dutta N, Helton SG, Schwandt M, Zhu X, Momenan R, Lohoff FW. Alcohol Clin Exp Res. 2016 Mar;40(3):474-81. doi: 10.1111/acer.12991. Epub 2016 Feb 15. PMID: 26876819

  10. Pharmacogenetics of alcohol use disorders and comorbid psychiatric disorders. Helton SG, Lohoff FW. Psychiatry Res. 2015 Dec 15;230(2):121-9. doi: 10.1016/j.psychres.2015.09.019. Epub 2015 Sep 14. Review. PMID:26455758

  11. Resting-state functional connectivity and presynaptic monoamine signaling in Alcohol Dependence. Zhu X, Dutta N, Helton SG, Schwandt M, Yan J, Hodgkinson CA, Cortes CR, Kerich M, Hall S, Sun H, Phillips M, Momenan R, Lohoff FW. Hum Brain Mapp. 2015 Dec;36(12):4808-18. doi: 10.1002/hbm.22951. Epub 2015 Sep 14. PMID: 26368063

  12. Clarke TK, Weiss AR, Ferarro TN, Kampman KM, Dackis CA, Pettinati HM, O'brien  CP, Oslin DW, Lohoff FW, Berrettini WH. The dopamine receptor D2 (DRD2) SNP rs1076560 is associated with opioid addiction. Ann Hum Genet. 2014 Jan;78(1):33-9. doi: 10.1111/ahg.12046. Epub 2013 Nov 25. PubMed PMID: 24359476;  PubMed Central PMCID: PMC4013426.

  13. Clarke TK, Crist RC, Ang A, Ambrose-Lanci LM, Lohoff FW, Saxon AJ, Ling W, Hillhouse MP, Bruce RD, Woody G, Berrettini WH. Genetic variation in OPRD1 and the response to treatment for opioid dependence with buprenorphine in European-American females. Pharmacogenomics J. 2014 Jun;14(3):303-8. doi: 10.1038/tpj.2013.30. Epub 2013 Oct 15. PubMed PMID: 24126707; PubMed Central PMCID: PMC3988270.

  14. Rickels K, Etemad B, Rynn MA, Lohoff FW, Mandos LA, Gallop R. Remission of generalized anxiety disorder after 6 months of open-label treatment with venlafaxine XR. Psychother Psychosom. 2013;82(6):363-71. doi: 10.1159/000351410.  Epub 2013 Sep 20. PubMed PMID: 24061331.

  15. Cooper AJ, Narasimhan S, Rickels K, Lohoff FW. Genetic polymorphisms in the PACAP and PAC1 receptor genes and treatment response to venlafaxine XR in generalized anxiety disorder. Psychiatry Res. 2013 Dec 30;210(3):1299-300. doi: 10.1016/j.psychres.2013.07.038. Epub 2013 Aug 22. PubMed PMID: 23972788.

  16. Cross-Disorder Group of the Psychiatric Genomics Consortium. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs.  Nat Genet. 2013 Sep;45(9):984-94. doi: 10.1038/ng.2711. Epub 2013 Aug 11. PubMed  PMID: 23933821; PubMed Central PMCID: PMC3800159.

  17. Tiwari AK, Need AC, Lohoff FW, Zai CC, Chowdhury NI, Müller DJ, Putkonen A, Repo-Tiihonen E, Hallikainen T, Yağcıoğlu AE, Tiihonen J, Kennedy JL, Meltzer HY. Exome sequence analysis of Finnish patients with clozapine-induced agranulocytosis. Mol Psychiatry. 2014 Apr;19(4):403-5. doi: 10.1038/mp.2013.74. Epub 2013 Jun 11. PubMed PMID: 23752246.

  18. Cooper AJ, Rickels K, Lohoff FW. Association analysis between the A118G polymorphism in the OPRM1 gene and treatment response to venlafaxine XR in generalized anxiety disorder. Hum Psychopharmacol. 2013 May;28(3):258-62. doi: 10.1002/hup.2317. Epub 2013 May 8. PubMed PMID: 23658070.

  19. Crist RC, Clarke TK, Ang A, Ambrose-Lanci LM, Lohoff FW, Saxon AJ, Ling W, Hillhouse MP, Bruce RD, Woody G, Berrettini WH. An intronic variant in OPRD1 predicts treatment outcome for opioid dependence in African-Americans. Neuropsychopharmacology. 2013 Sep;38(10):2003-10. doi: 10.1038/npp.2013.99. Epub  2013 Apr 23. Erratum in: Neuropsychopharmacology. 2014 Mar;39(4):1039. PubMed PMID: 23612435; PubMed Central PMCID: PMC3746708.

  20. Clarke TK, Crist RC, Kampman KM, Dackis CA, Pettinati HM, O'Brien CP, Oslin DW, Ferraro TN, Lohoff FW, Berrettini WH. Low frequency genetic variants in the μ-opioid receptor (OPRM1) affect risk for addiction to heroin and cocaine. Neurosci Lett. 2013 May 10;542:71-5. doi: 10.1016/j.neulet.2013.02.018. Epub 2013 Feb 20. PubMed PMID: 23454283; PubMed Central PMCID: PMC3640707.

  21. Cross-Disorder Group of the Psychiatric Genomics Consortium. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet. 2013 Apr 20;381(9875):1371-9. doi: 10.1016/S0140-6736(12)62129-1. Epub 2013 Feb 28. Erratum in: Lancet. 2013 Apr 20;381(9875):1360. PubMed PMID: 23453885; PubMed Central PMCID: PMC3714010.

  22. Lohoff FW, Hodge R, Narasimhan S, Nall A, Ferraro TN, Mickey BJ, Heitzeg MM,  Langenecker SA, Zubieta JK, Bogdan R, Nikolova YS, Drabant E, Hariri AR, Bevilacqua L, Goldman D, Doyle GA. Functional genetic variants in the vesicular monoamine transporter 1 modulate emotion processing. Mol Psychiatry. 2014 Jan;19(1):129-39. doi: 10.1038/mp.2012.193. Epub 2013 Jan 22. PubMed PMID: 23337945.

  23. Multani PK, Hodge R, Estévez MA, Abel T, Kung H, Alter M, Brookshire B, Lucki I, Nall AH, Talbot K, Doyle GA, Lohoff FW. VMAT1 deletion causes neuronal loss in the hippocampus and neurocognitive deficits in spatial discrimination. Neuroscience. 2012 Nov 29;232C:32-44. doi: 10.1016/j.neuroscience.2012.11.023. [Epub ahead of print] PubMed PMID: 23201251.

  24. Wetherill RR, Jagannathan K, Lohoff FW, Ehrman R, O'Brien CP, Childress AR, Franklin TR. Neural correlates of attentional bias for smoking cues: modulation by variance in the dopamine transporter gene. Addict Biol. 2014 Mar;19(2):294-304. doi: 10.1111/j.1369-1600.2012.00507.x. Epub 2012 Oct 12. PubMed PMID: 23061530; PubMed Central PMCID: PMC4052978.

  25. Multani PK, Clarke TK, Narasimhan S, Ambrose-Lanci L, Kampman KM, Pettinati HM, Oslin DW, O'Brien CP, Berrettini WH, Lohoff FW. Neuronal calcium sensor-1 and cocaine addiction a genetic association study in African-Americans and European  Americans. Neurosci Lett. 2012 Nov 30;531(1):46-51. doi: 10.1016/j.neulet.2012.09.014. Epub 2012 Sep 20. PubMed PMID: 22999924; PubMed Central PMCID: PMC3895491.

  26. Lohoff FW, Narasimhan S, Rickels K. Interaction between polymorphisms in serotonin transporter (SLC6A4) and serotonin receptor 2A (HTR2A) genes predict treatment response to venlafaxine XR in generalized anxiety disorder. Pharmacogenomics J. 2013 Oct;13(5):464-9. doi: 10.1038/tpj.2012.33. Epub 2012 Aug 21. PubMed PMID: 22907732.

  27. Crist RC, Ambrose-Lanci LM, Vaswani M, Clarke TK, Zeng A, Yuan C, Ferraro TN, Hakonarson H, Kampman KM, Dackis CA, Pettinati HM, O'Brien CP, Oslin DW, Doyle GA, Lohoff FW, Berrettini WH. Case-control association analysis of polymorphisms  in the δ-opioid receptor, OPRD1, with cocaine and opioid addicted populations. Drug Alcohol Depend. 2013 Jan 1;127(1-3):122-8. doi: 10.1016/j.drugalcdep.2012.06.023. Epub 2012 Jul 12. PubMed PMID: 22795689; PubMed Central PMCID: PMC3509227.

  28. Clarke TK, Ambrose-Lanci L, Ferraro TN, Berrettini WH, Kampman KM, Dackis CA, Pettinati HM, O'Brien CP, Oslin DW, Lohoff FW. Genetic association analyses of PDYN polymorphisms with heroin and cocaine addiction. Genes Brain Behav. 2012 Jun;11(4):415-23. doi: 10.1111/j.1601-183X.2012.00785.x. Epub 2012 Apr 11. PubMed PMID: 22443215.

  29. Narasimhan S, Aquino TD, Multani PK, Rickels K, Lohoff FW. Variation in the catechol-O-methyltransferase (COMT) gene and treatment response to venlafaxine XR in generalized anxiety disorder. Psychiatry Res. 2012 Jun 30;198(1):112-5. doi: 10.1016/j.psychres.2011.12.034. Epub 2012 Mar 13. PubMed PMID: 22417933.

  30. Lohoff FW, Aquino TD, Narasimhan S, Multani PK, Etemad B, Rickels K. Serotonin receptor 2A (HTR2A) gene polymorphism predicts treatment response to venlafaxine XR in generalized anxiety disorder. Pharmacogenomics J. 2013 Feb;13(1):21-6. doi: 10.1038/tpj.2011.47. Epub 2011 Oct 18. PubMed PMID: 22006095.

  31. Psychiatric GWAS Consortium Bipolar Disorder Working Group. Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nat Genet. 2011 Sep 18;43(10):977-83. doi: 10.1038/ng.943. Erratum in: Nat Genet. 2012 Sep;44(9):1072. Fullerton, Janice M [added]; Hyoun, Phil L [corrected to Lee, Phil H]; Meng, Fan Guo [corrected to Meng, Fan]. PubMed PMID: 21926972; PubMed Central PMCID: PMC3637176.

  32. Clarke TK, Bloch PJ, Ambrose-Lanci LM, Ferraro TN, Berrettini WH, Kampman KM, Dackis CA, Pettinati HM, O'Brien CP, Oslin DW, Lohoff FW. Further evidence for association of polymorphisms in the CNR1 gene with cocaine addiction: confirmation in an independent sample and meta-analysis. Addict Biol. 2013 Jul;18(4):702-8. doi: 10.1111/j.1369-1600.2011.00346.x. Epub 2011 Jul 25. PubMed  PMID: 21790903; PubMed Central PMCID: PMC3223560.

  33. Franklin TR, Wang Z, Li Y, Suh JJ, Goldman M, Lohoff FW, Cruz J, Hazan R, Jens W, Detre JA, Berrettini W, O'Brien CP, Childress AR. Dopamine transporter genotype modulation of neural responses to smoking cues: confirmation in a new cohort. Addict Biol. 2011 Apr;16(2):308-22. doi: 10.1111/j.1369-1600.2010.00277.x. Epub 2011 Feb 8. PubMed PMID: 21299752; PubMed  Central PMCID: PMC3348624.

  34. Wiener M, Lohoff FW, Coslett HB. Double dissociation of dopamine genes and timing in humans. J Cogn Neurosci. 2011 Oct;23(10):2811-21. doi: 10.1162/jocn.2011.21626. Epub 2011 Jan 24. PubMed PMID: 21261454.

  35. Rickels K, Etemad B, Khalid-Khan S, Lohoff FW, Rynn MA, Gallop RJ. Time to relapse after 6 and 12 months' treatment of generalized anxiety disorder with venlafaxine extended release. Arch Gen Psychiatry. 2010 Dec;67(12):1274-81. doi:  10.1001/archgenpsychiatry.2010.170. PubMed PMID: 21135327.

  36. Smith EN, Bloss CS, Badner JA, Barrett T, Belmonte PL, Berrettini W, Byerley  W, Coryell W, Craig D, Edenberg HJ, Eskin E, Foroud T, Gershon E, Greenwood TA, Hipolito M, Koller DL, Lawson WB, Liu C, Lohoff F, McInnis MG, McMahon FJ, Mirel  DB, Murray SS, Nievergelt C, Nurnberger J, Nwulia EA, Paschall J, Potash JB, Rice J, Schulze TG, Scheftner W, Panganiban C, Zaitlen N, Zandi PP, Zöllner S, Schork  NJ, Kelsoe JR. Genome-wide association study of bipolar disorder in European American and African American individuals. Mol Psychiatry. 2009 Aug;14(8):755-63. doi: 10.1038/mp.2009.43. Epub 2009 Jun 2. PubMed PMID: 19488044; PubMed Central PMCID: PMC3035981.

  37. Lohoff FW, Bloch PJ, Ferraro TN, Berrettini WH, Pettinati HM, Dackis CA, O'Brien CP, Kampman KM, Oslin DW. Association analysis between polymorphisms in the conserved dopamine neurotrophic factor (CDNF) gene and cocaine dependence. Neurosci Lett. 2009 Apr 10;453(3):199-203. doi: 10.1016/j.neulet.2009.02.026. Epub 2009 Feb 21. PubMed PMID: 19429035; PubMed Central PMCID: PMC2680755.

  38. Lohoff FW, Weller AE, Bloch PJ, Nall AH, Ferraro TN, Kampman KM, Pettinati HM, Oslin DW, Dackis CA, O'Brien CP, Berrettini WH. Association between the catechol-O-methyltransferase Val158Met polymorphism and cocaine dependence. Neuropsychopharmacology. 2008 Dec;33(13):3078-84. doi: 10.1038/npp.2008.126. Epub 2008 Aug 13. PubMed PMID: 18704099; PubMed Central PMCID: PMC2583214.

  39. Lohoff FW, Bloch PJ, Weller AE, Nall AH, Doyle GA, Buono RJ, Ferraro TN, Kampman KM, Pettinati HM, Dackis CA, Oslin DW, O'Brien CP, Berrettini WH. Genetic variants in the cocaine- and amphetamine-regulated transcript gene (CARTPT) and cocaine dependence. Neurosci Lett. 2008 Aug 8;440(3):280-3. doi: 10.1016/j.neulet.2008.05.073. Epub 2008 May 24. PubMed PMID: 18572320; PubMed Central PMCID: PMC2507865.

  40. Lohoff FW, Lautenschlager M, Mohr J, Ferraro TN, Sander T, Gallinat J. Association between variation in the vesicular monoamine transporter 1 gene on chromosome 8p and anxiety-related personality traits. Neurosci Lett. 2008 Mar 21;434(1):41-5. doi: 10.1016/j.neulet.2008.01.024. Epub 2008 Jan 16. PubMed PMID: 18249496.

  41. Lohoff FW, Sander T, Ferraro TN, Dahl JP, Gallinat J, Berrettini WH. Confirmation of association between the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene and bipolar I disorder. Am J Med Genet B Neuropsychiatr Genet. 2005 Nov 5;139B(1):51-3. PubMed PMID: 16152572.

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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