https://www.andrewglazerlab.com/home daily 0.75 2021-07-02 https://images.squarespace-cdn.com/content/v1/5ce46ee21028260001017459/1562683039814-1T3CWN123QW4ZGCBINOP/Logo2.png Home https://images.squarespace-cdn.com/content/v1/5ce46ee21028260001017459/1562683039817-RXKCUKQO2ABWUZLBWJHU/Logo1.png Home https://images.squarespace-cdn.com/content/v1/5ce46ee21028260001017459/1562683039863-FLYULYTF7W5OZDGOXZV3/Logo3.png Home https://images.squarespace-cdn.com/content/v1/5ce46ee21028260001017459/1562683039860-0KG8P7FIY9YAWHIXIWBO/Logo4.png Home https://images.squarespace-cdn.com/content/v1/5ce46ee21028260001017459/1558539494963-0E0FMXUPKSCMVQM4YU9B/20170619S1_Professional_Trainer_Trainee_Portrait_007.jpg Home https://images.squarespace-cdn.com/content/v1/5ce46ee21028260001017459/1558542208930-6V5B1K06RCTVRS45Q1RB/20170619S1_Professional_Trainer_V_Stretch_145.jpg Home - Warm Up Work Out Cool Down Proper stretching and cool down routines will help you maximize your workouts and get noticeable results fast. https://images.squarespace-cdn.com/content/v1/5ce46ee21028260001017459/1558542263461-4TS2NHWHUXXZMIE37PX6/20170619S1_Professional_Trainer_Trainers_Feet_004.jpg Home - A Constant Source of Motivation Think of me as your personal cheering section, helping you find the strength you didn’t know you had. I’m all about positive reinforcement. https://www.andrewglazerlab.com/research daily 0.75 2022-03-17 https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/1625675307980-U0TAWXV1P9MT8FL6O0QV/Fig4+emerge_penetrance_barplots_byvariant6-01.png Research - Biobank genetic studies We use large biobank datasets with participant genotypes and disease phenotypes to identify new variants linked to disease. These biobanks include Vanderbilt’s pioneering BioVU biobank, the eMERGE Network, the UK Biobank, and All of Us (>1M total participants). We use innovative phenotyping methods to discover associations between variants in transmembrane proteins and disease. These variants are then studied in vitro (see below). Example paper: Arrhythmia variant associations and reclassifications in the eMERGE-III sequencing study https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/1625673069549-50GQL57S5HUK9AO1NLBG/syncropatch+2+pics-01.jpg Research - Automated patch clamping Ion channels pass ions through the cell membrane in a regulated fashion and are important for many biological processes and diseases. We use automated patch clamping to characterize ion channel mutations in high-throughput. The SyncroPatch patch clamp instrument allows us to study 384 wells in a 30 minute experiment. To date we have studied >250 variants with this approach. One main focus is cardiac ion channels linked to Mendelian arrhythmia syndromes. A major future direction will be to mutations in a broad set of other “channelopathy” genes—ion channel genes where mutations lead to Mendelian syndromes. Example paper: High-throughput reclassification of SCN5A variants https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/1625676134817-O6IH7MPFGXVZUO6ULS2Y/dms+pilot+for+website+no+letters-01.png Research - Deep Mutational Scans Deep mutational scans are comprehensive screens of nearly every mutation in a gene, using high-throughput sequencing of mutant libraries coupled to in vitro assays. They can create a prospective list of all variants that disrupt function in important disease genes. We are deploying scans of cardiac ion channel genes linked to arrhythmia syndromes. We are also expanding to other transmembrane proteins, using a general cell surface trafficking assay. Example paper: Deep mutational scan of an SCN5A voltage sensor https://www.andrewglazerlab.com/publications daily 0.75 2026-02-06 https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/43651644-d749-40ba-b914-f9a37991b2a5/EHJ+graphical+abstract.png https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/db0ebbeb-c5bf-4af6-98c1-876c2c218f14/parse-seq+figure.png https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/1e58bab7-348c-47e3-a5dd-3b4d21bec97e/Peak+current+ACMG+calibration.png https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/86cd28ec-c7e6-4bff-98b7-b4f79921471b/KCNE1_forwebsite2-01.png https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/f0902f23-9cb7-435d-b371-d04fce8927c0/Oneill+splice+summary+for+website.png Publications - Functional Assays Reclassify Suspected Splice-Altering Variants of Uncertain Significance in Mendelian Channelopathies. Pubmed Circulation: Genomics and Precision Medicine (2022) O’Neill M, Wada Y, Hall L, Mitchell D, Glazer A*, Roden D.* (*co-corresponding) We studied 13 variants in cardiac ion channel genes that were near splice sites. We used two assays: CRISPR of induced pluripotent stem cell-derived cardiomyocytes and splicing minigene assays. We found that 9/13 variants had splice-disrupting effects and could be reclassified. https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/9dc6968b-0b34-469d-bbf7-3bdbb427aeb0/DN+A735E+example+pic.png Publications - Dominant negative effects of SCN5A missense variants. Pubmed Genetics in Medicine (2022) O’Neill M, Muhammad A, Li B, Wada Y, Hall L, Solus J, Short L, Roden D, Glazer A. Surprisingly, the cardiac ion channel SCN5A was recently shown to dimerize. Here we find widespread dominant negative effects for >30 SCN5A loss of function variants. These variants cause an especially high rate of arrhythmias. https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/1625270498455-36NMTF972YJ13CIL52TR/emerge+figure.png Publications Arrhythmia variant associations and reclassifications in the eMERGE-III sequencing study. Pubmed VUMC Reporter Circulation (2022) Glazer A, Davogustto G*, Shaffer C, Vanoye C, Desai R, Farber-Eger E, Dikilitas O, Shang N, Pacheco J, Yang T, Muhammad A, Mosley J, Van Driest S, Wells Q, Shaffer L, Kalash O, Wada Y, Bland S, Yoneda Z, Mitchell D, Kroncke B, Kullo I, Jarvik G, Gordon A, Larson E, Manolio T, Mirshahi T, Luo J, Schaid D, Namjou B, Alsaied T, Singh R, Singhal A, Liu C, Weng C, Hripcsak G, Ralston J, McNally E, Chung W, Carrell D, Leppig K, Hakonarson H, Sleiman P, Sohn S, Glessner J, Denny J, Wei W, George A, Shoemaker M, Roden D. *Contributed equally. What happens when you sequence arrhythmia genes in >20K people? Dozens of pathogenic variants, new diagnoses, and high-throughput in vitro studies. https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/1625269937868-O2OVQRVERZO879RS1XAP/AJHG+figure-02.png Publications - High-throughput reclassification of SCN5A variants. Pubmed Discover Magazine Glazer A, Wada Y, Li B, Muhammad A, Kalash O, O’Neill M, Shields T, Hall L, Short L, Blair M, Kroncke B, Capra J, Roden D. American Journal of Human Genetics (2020). Winner of Cotterman award for paper of the year from a postdoctoral fellow in AJHG. We used high-throughput automated patch clamping to study the function of 83 variants in the cardiac sodium channel, SCN5A. We found 44 new loss of function variants and reclassified a majority of studied Variants of Uncertain Significance. https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/1625271919550-2PFE3QNRUQ0MMCVZVZUL/Figure+3+for+website-01.png Publications Deep Mutational Scan of an SCN5A voltage sensor. Pubmed Glazer A, Kroncke B, Matreyek K, Yang T, Wada Y, Shields T, Salem J, Fowler D, Roden D. Circulation Genomic and Precision Medicine (2020). Cover article. Mutations in the cardiac sodium channel SCN5A can cause arrhythmias, but most are Variants of Uncertain Signficance. We implemented a Deep Mutational Scan of nearly every mutation in a 36-base region of SCN5A. Using high-throughput sequencing and a multiplexed cell death assay, we discovered novel gain and loss of function variants. We are currently scaling this work up to the whole protein. https://www.andrewglazerlab.com/people daily 0.75 2025-02-09 https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/3fb4ee89-159e-48f8-9523-28b431c842cb/Glazer_Andrew+2+cropped+for+website.jpg People - Andrew Glazer, Ph.D. Assistant Professor Andrew is a geneticist interested in understanding which mutations underlie rare Mendelian diseases. He got his undergraduate degree at MIT, his PhD at the University of California-Berkeley, and his postdoctoral fellowship at Vanderbilt. His favorite hobbies are juggling and playing chess. Email Twitter LinkedIn ORCID Pubmed https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/6d28f5b1-07a5-4568-850b-ca408cfcd804/thumbnail_MurphyJessa.jpg https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/60aa0b03-a605-4884-a478-86f6d6a77b52/Dolder_image+cropped.jpeg https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/293815ca-3e65-41fe-b288-5ce2634d541f/EOsborn_image+cropped.jpeg https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/cda437ab-dd1a-4a19-8ba1-0d7ee202ceff/Smith_Jeremy+headshot+cropped.JPG https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/13c63a9c-109c-4db5-8244-b1c35c46fc50/Sophie+headshot.jpg People - Sophie Cohen Research Assistant Sophie graduated from Vanderbilt with a major in Molecular and Cellular Biology. She is interested in genetic diseases, especially those that are hereditary, and wants to pursue a career in genetic counseling. Her favorite things to do in her free time are reading and singing. https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/42e57cec-6289-4e7b-8547-3ba903bf32cf/paige+roberson+headshot.png https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/1f78eb53-af12-456d-8e3b-55e2a10039a5/Sasha+Barrera+headshot+cropped.jpeg https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/4a1f99ff-dce3-4b10-a26e-870641f5102b/Marlyssa+Headshot+cropped.jpg https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/1625266565965-LBHNNLKGFX0D6E0B4DGE/mystery+person.jpeg People - You? Want to join a new, exciting lab in lovely Nashville, Tennessee? We are currently looking for postdocs and graduate students to join the lab. Please contact Dr. Glazer (andrew.m.glazer[at]vumc.org) if you are interested! https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/1625273391269-E5QGYHECW3UH92FG3TNH/ONeill+2+cropped.jpg People - Matthew O’Neill M.D.-Ph.D. student Matthew was an M.D.-Ph.D. student who worked closely with the Glazer Lab. He previously trained in synthetic organic chemistry and now seeks to combine this background with genetics to advance pre-clinical therapeutic discovery. He studied the effect of mutations on RNA splicing, and performed various other arrhythmia genetics studies in the lab. Matt is now an internal medicine resident at Brigham and Woman’s Hospital. https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/1625273339335-Q7JHV8233ARL3GSQR0UZ/ayesha2+cropped.jpeg People - Ayesha Muhammad M.D.-Ph.D. student Ayesha was an M.D.-Ph.D. student who worked closely with the Glazer Lab. She performed high-throughput in vitro studies of cardiac arrhythmia variants, including a multiplexed scan of thousands of variants. She is currently doing her residency in anesthesiology at the University of Michigan. Twitter LinkedIn ORCID https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/ade59811-3e18-418e-a446-3d8e1f942c7a/Ryder+Headshot+cropped.png https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/963d4cc5-a3be-489b-8801-34a886e31bf7/Zerubabell+Headshot+2023+cropped.jpeg https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/5f045fc5-3648-450b-b7c1-4127171e8c4f/Maria+profile+pic.jpg People - Maria Calandranis Research Assistant Maria was a research assistant in the lab with an interest in genetic studies and how they can impact clinical and ecological issues. She is currently performing cancer research at the University of Wisconsin. https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/13337695-939c-402c-bdd8-56652ce44120/Kara+headshot+cropped.jpeg People Kara Skorge Research Assistant Kara was a research assistant who assisted with cell culture work, cloning experiments, and administrative tasks. She is now a genetic counseling student at the University of Pennsylvania. https://images.squarespace-cdn.com/content/v1/5fbaf84b476e5f5748f1ef26/523a82d9-499e-43ff-9a69-41756d30d376/Ashli+Headshot+cropped.jpg People - Ashli Chew Research Assistant Ashli was a research assistant in the lab who helped with cell culture, cloning, and administrative support. 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