Draft:Luda Diatchenko

Luda Diatchenko
Born	Moscow, Russia
Occupation(s)	Professor, McGill University
Known for	Identifying “pain genes” and biological pathways contributing to human pain
Awards	Fellow of the Royal Society of Canada
Academic background
Education	MD and MS, Russian State Medical University, PhD (Molecular Biology), Russian State Medical University; National Cardiology Research Center
Academic work
Discipline	Molecular Genetics
Sub-discipline	Human Pain Genetics
Institutions	Alan Edwards Centre for Research on Pain, McGill University, Montreal
Notable ideas	Genetic variants of COMT associated with pain sensitivity and the risk of chronic pain conditions; protective role of neutrophil-driven inflammation for pain resolution; individual differences in responses to analgesic drugs driven by genetics
Website	Human Pain Genetics Lab

Luda Diatchenko is an academic and researcher at McGill University in Quebec, Canada, with a research focus on pain in humans. She is the Canada Excellence Research Chair (CERC) in Human Pain Genetics Laureat and the Fellow of the Royal Society of Canada.

Education

Diatchenko grew up and completed her studies in Moscow, Russia. She completed her MD and Master of Science (Biochemistry) in 1990 from the Russian State Medical University (now known as the Pirogov Russian National Research Medical University). She continued her studies here and at the National Cardiology Research Center, and was awarded a PhD in Molecular Biology in 1993. She undertook postdoctoral studies in 1994-1995 at CLONTECH Laboratories (now Takara Bio USA) in Palo Alto, California.

Research and career

Diatchenko began her career in industry with 5 year in research and development at CLONTECH Laboratories after her postdoctoral studies. In 2000, her career in academia began as a Visiting Research Assistant Professor at the Center for Neurosensory Disorders at the University of North Carolina, Chapel Hill. She has continued since then to have roles in both academia and industry. Between 2000 – 2013, she led her research group at the University of North Carolina, becoming a Professor in 2013. Since 2013, she has led a research group at McGill University, in Montreal, Canada, in the Alan Edwards Centre for Research on Pain and in the Department of Anesthesia, Faculty of Medicine and Faculty of Dental Medicine and Oral Health Sciences. Her recruitment to McGill included a Canada Excellence Research Chair (CERC), which facilitated her work in creating a Human Pain Genetics Program at McGill. She continues to be involved in industry research through advisory board membership or as a consultant.

Diatchenko pioneered the field of human pain genetics, where she has substantively contributed to the current body of knowledge through her work. Her work has covered genetics and pharmaceutics. Diatchenko has been instrumental in identifying new pain drug targets through a reverse genetic approach that starts with human genetics and genomics, which has led to discovering pain genes and biological pathways that contribute to human pain. Research here has revealed a genetic variation in the human catechol-O-methyltransferase gene with pain sensitivity and the risk of chronic pain conditions (Hum. Mol. Genet., 2004; Science, 2006), the protective role of neutrophil-driven inflammation for pain resolution in patients with acute lower back pain, where inhibiting inflammation leads to short-term analgesia but long-term pain states (Sci.Transt.Med., 2022), and individual differences in responses to analgesic drugs being driven by genetics (Hum. Mol. Genet., 2009; Pain, 2020).

Diatchenko also believes in and contributes to open science to advance our understanding of the molecular mechanisms of pain. Her lab’s Human Pain Genetics Database (HPGdb) summarizes all extant data on the genetic contributors of pain and the Transcriptomics Pain Signatures Database (PSGS) summarizes all available data on genome-wide transcriptomics in human pain conditions and experimental pain models. Diatchenko has also been prolific in developing molecular genetic methodologies. She pioneered Suppression Subtractive Hybridization (SSH) nearly 30 years ago, which is still widely used and highly cited times (: Proc. Natl. Acad. Sci., U.S.A., 1996). She and colleagues have also developed a SMART technology (Biochem Biophys Res Commun., 1997) factorial reporter system that measures the activities of multiple transcription factors in a living cell.

Diatchenko has been an active member of several professional societies, such as the International Association for the Study of Pain (IASP), playing various roles in multiple committees. At IASP, in 2012, she founded and was Elected Chair of the Special Interest Group (SIG) in Genetics and Pain. She also consults for policy-making agencies such as the National Institutes of Health, the US National Academy of Sciences and the US Surgeon General Office.

Awards and honors

• 2023: Fellow, Academy of Science, Royal Society of Canada
• 2022: Fellow, Canadian Academy of Health Sciences
• 2021: Canada Research Chair Tier 1 – Human Pain Genetics
• 2022: Ronald Melzack Lecture Award by the International Association for the Study of Pain (IASP)
• 2021: NIH Director’s Wednesday Afternoon Lecture Series Award
• 2019: Honourary Skou Professor from Aarhus University
• 2013: Canada Excellence Research Chair (CERC) in Human Pain Genetics

Bibliography

• Ao X, Parisien M, Fillingim RB, Ohrbach R, Slade GD, Diatchenko L, Smith SB. Whole-genome methylation profiling reveals regionsassociated with painful temporomandibular disorders and active recovery processes. Pain. 2023 Nov 28. doi: 10.1097/j.pain.0000000000003104. PMID: 38015635
• Tanguay-Sabourin C, Fillingim M, Guglietti GV, Zare A, Parisien M, Norman J, Sweatman H, Da-Ano R, Heikkala E; PREVENT-AD Research Group; Perez J, Karppinen J, Villeneuve S, Thompson SJ, Martel MO, Roy M, Diatchenko L, Vachon-Presseau E. A prognostic risk score for development and spread of chronic pain. Nat. Med. 2023 July 6. doi: 10.1038/s41591-023-02430-4. E-pub.
• Jahangiri Esfahani S., Parisien M., Surbey C., Diatchenko L. The Transcriptomics Pain Signature Database. BioRxiv 2023 June 18. doi.org/10.1101/2023.06.16.545337
• Ao X, Parisien M, Zidan M, Grant AV, Martinsen AE, Winsvold BS, Diatchenko L. Rare variant analyses in large-scale cohorts identified SLC13A1 associated with chronic pain. Pain 2023 Mar 22. doi: 10.1097/j.pain.0000000000002882. PMID: 36943258
• Parisien M, Lima LV, Dagostino C, El-Hachem N, Drury GL, Grant AV, Huising J, Verma V, Meloto CB, Silva JR, Dutra GGS, Markova T, Dang H, Tessier PA, Slade GD, Nackley AG, Ghasemlou N, Mogil JS, Allegri M, Diatchenko L. Acute inflammatory response via neutrophil activation protects against the development of chronic pain. Science Translational Medicine. 2022 11 May 2022 (Vol 14, Issue 644) DOI: 10.1126/scitranslmed.abj9954. PMID: 35544595
• Khoury S., Parisien M., Thompson SJ., Vachon-Presseau E., Roy M., Martinsen AE, Winsvold BS, HUNT All-In Pain, Mundal IP, Zwart J-A, Kania A, Mogil JS, Diatchenko L. Genome-wide analysis identifies impaired axonogenesis in chronic overlapping pain conditions. Brain. 2022 March (Volume 145, Issue 3, March 2022, Pages 1111–1123) DOI:10.1093/brain/awab359. PMID: 34788396
• Verma V., Drury G., Parisien M., Özdağ A, Ayşe N, Al-Aubodah, Tho-Alfakar; Nijnik, A., wen X., Tugarinov N., Verner M, Klares R., Linton A., Krock E., Morado U., Carlos E, Winsvold B, Fritsche LG., Fors EA., Piccirillo C, Khoutorsky A, Svensson CI, Fitzcharles M, Ingelmo P., Bernard NF., Dupuy FP., Üçeyler N., Sommer C., King IL., Meloto CB., Diatchenko L., HUNT-All In Pain. Unbiased immune profiling reveals a natural killer cell-peripheral nerve axis in fibromyalgia. Pain. 2021 September 24, Online ahead of print, PMID: 34913882
• Muralidharan A, Samoshkin A, Convertino M, Piltonen MH, Gris P, Wang J, Jiang C, Klares R 3rd, Linton A, Ji RR, Maixner W, Dokholyan NV, Mogil JS, Diatchenko L. Identification and characterization of novel candidate compounds targeting 6- and 7-transmembrane mu-opioid receptor isoforms. Br J Pharmacol. 2021 Jul;178(13):2709-2726 PMID: 33782947

• Benavides R, Vsevolozhskaya O, Cattaneo S, Zaykin D, Brenton A, Parisien M, Verma V, Khoury S, Gilron I, Diatchenko L.A functionalpolymorphism in the ATP-Binding Cassette B1 transporter predicts pharmacologic response to combination of nortriptyline and morphine in neuropathic pain patients. Pain. 2020 Mar;161(3):619-629. doi: 10.1097/j.pain.0000000000001750. PMID: 31738228
• Smith SB, Parisien M, Bair E, Belfer I, Chabot-Doré AJ, Gris P, Khoury S, Tansley S, Torosyan Y, Zaykin DV, Bernhardt O, de Oliveira Serrano P, Gracely RH, Jain D, Järvelin MR, Kaste LM, Kerr KF, Kocher T, Lähdesmäki R, Laniado N, Laurie CC, Laurie CA, Männikkö M, Meloto CB, Nackley AG, Nelson SC, Pesonen P, Ribeiro-Dasilva MC, Rizzatti-Barbosa CM, Sanders AE, Schwahn C, Sipilä K, Sofer T, Teumer A, Mogil JS, Fillingim RB, Greenspan JD, Ohrbach R, Slade GD, Maixner W, Diatchenko L. Genome-wide association reveals contribution of MRAS to painful temporomandibular disorder in males. Pain. 2019 Mar;160(3):579-591. PMID: 30431558; PMCID: PMC6377338.
• Meloto CB, Benavides R, Lichtenwalter RN, Wen X, Tugarinov N, Zorina-Lichtenwalter K, Chabot-Doré AJ, Piltonen MH, Cattaneo S, Verma V, Klares R 3rd, Khoury S, Parisien M, Diatchenko L. Human pain genetics database: a resource dedicated to human pain genetic research. Pain. 2018 Apr;159(4):749-763. PMID: 29300278.
• Martin LJ, Smith SB, Khoutorsky A, Magnussen CA, Samoshkin A, Sorge RE, Cho C, Yosefpour N, Sivaselvachandran S, Tohyama S, Cole T, Khuong TM, Mir E, Gibson DG, Wieskopf JS, Sotocinal SG, Austin JS, Meloto CB, Gitt JH, Gkogkas C, Sonenberg N, Greenspan JD, Fillingim RB, Ohrbach R, Slade GD, Knott C, Dubner R, Nackley AG, Ribeiro-da-Silva A, Neely GG, Maixner W, Zaykin DV, Mogil JS, Diatchenko L. Epiregulin and EGFR interactions are involved in pain processing. J Clin Invest. 2017 Sep 1;127(9):3353-3366. PMID: 28783046; PMCID: PMC5669538.
• Parisien M, Khoury S, Chabot-Doré AJ, Sotocinal SG, Slade GD, Smith SB, Fillingim RB, Ohrbach R, Greenspan JD, Maixner W, Mogil JS, Belfer I, Diatchenko L. Effect of Human Genetic Variability on Gene Expression in Dorsal Root Ganglia and Association with Pain Phenotypes. Cell Rep. 2017 May 30;19(9):1940-1952. PMID: 28564610; PMCID: PMC5524461. Diatchenko L, Nackley AG, Tchivileva IE, Shabalina SA, Maixner W. Genetic architecture of human pain perception. Trends Genet. 2007 Dec;23(12):605-13. doi: 10.1016/j.tig.2007.09.004. PMID: 18023497 Review.
• Shabalina SA, Zaykin DV, Gris P, Ogurtsov AY, Gauthier J, Shibata K, Tchivileva IE, Belfer I, Mishra B, Kiselycznyk C, Wallace MR, Staud R, Spiridonov NA, Max MB, Goldman D, Fillingim RB, Maixner W, Diatchenko L. Expansion of the human mu-opioid receptor gene architecture: novel functional variants. Hum Mol Genet. 2009 Mar 15;18(6):1037-51. doi: 10.1093/hmg/ddn439. PMID: 19103668
• Romanov S, Medvedev A, Gambarian M, Poltoratskaya N, Moeser M, Medvedeva L, Gambarian M, Diatchenko L, Makarov S. Homogeneous reporter system enables quantitative functional assessment of multiple transcription factors. Nat Methods. 2008 Mar;5(3):253-60. doi: 10.1038/nmeth.1186. PMID: 18297081
• Nackley AG, Shabalina SA, Tchivileva IE, Satterfield K, Korchynskyi O, Makarov SS, Maixner W, Diatchenko L. Human catechol-O- methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure. Science. 2006 Dec 22;314(5807):1930-3. doi: 10.1 126/science.1131262. PMID: 17185601
• Diatchenko L, Slade GD, Nackley AG, Bhalang K, Sigurdsson A, Belfer I, Goldman D, Xu K, Shabalina SA, Shagin D, Max MB, Makarov SS, Maixner W. Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet. 2005 Jan 1;14(1):135-43. doi: 10.1093/hmg/ddi013. PMID: 15537663
• Lukyanov K, Diatchenko L, Chenchik A, Nanisetti A, Siebert P, Usman N, Matz M, Lukyanov S. Construction of cDNA libraries from smallamounts of total RNA using the suppression PCR effect. Biochem Biophys Res Commun. 1997 Jan 13;230(2):285-8. doi: 10.1006/bbrc.1996.5948. PMID: 9016767
• Diatchenko L, Lau YF, Campbell AP, Chenchik A, Moqadam F, Huang B, Lukyanov S, Lukyanov K, Gurskaya N, Sverdlov ED, Siebert PD. Suppression subtractive hybridization: a method for generating differentially regulated or tissue-specific cDNA probes and libraries. Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):6025-30. doi: 10.1073/pnas.93.12.6025. PMID: 8650213

External links

• Human Pain Genetics Lab
• Transcriptomics Pain Signatures Database
• Human Pain Genes Database