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News in 2023

July 2023

Training for lab members. Joanna L. and Kirill attend the MS Summer School in Madison, WI, and Francesca attends the Skyline User course in Seattle, WA.

The lab welcomes two new postdocs to the group, Carolina Bras and Bibhuti Palai!

June 2023

The Garcia Lab returns from a successful ASMS Conference. Several members presented posters, and Ben, Joanna L. and Axe gave user meetings talks.

Congrats to Axe for winning the ASMS Postdoctoral Career Development Award.

Congrats to Francisca for winning a BMB Department Professional Devlopment Award

The lab welcomes our newest graduate student to the lab, Kirill Miachin, who will be working on his MD/PhD.

May 2023

Congrats to Tom for being selected as a BMB Department Research Seed grant winner.

March 2023

The Garcia Lab returns from a great US HUPO Conference where we had several poster and lightning talk presentations. Ben wins a best lightning talk award for his “histone rap”.

New tools for RNA sequencing and modification mapping are published in Analytical Chemistry.

January 2023

The Garcia lab welcomes Joanna G. (Joey) to the lab as our new Technician.

Joanna L. publishes a review on histone modification crosstalk in the Biochemical Journal.

Latest Publications

Garcia Lab Publications

Circular Engineered Sortase for Interrogating Histone H3 in Chromatin November 25, 2024
Reversible modification of the histone H3 N-terminal tail is critical in regulating the chromatin structure, gene expression, and cell states, while its dysregulation contributes to disease pathogenesis. Understanding the crosstalk between H3 tail modifications in nucleosomes constitutes a central challenge in epigenetics. Here, we describe an engineered sortase transpeptidase, cW11, that displays highly favorable properties […]
Neuropeptides specify and reprogram division of labor in the leafcutter ant <em>Atta cephalotes</em> November 22, 2024
Social insects offer powerful models to investigate the mechanistic foundation of elaborate individual behaviors comprising a cooperative community. Workers of the leafcutter ant genus Atta provide an extreme example of behavioral segregation among many phenotypically distinct worker types. We utilize the complex worker system of Atta cephalotes to test the molecular underpinnings of behavioral programming […]
Metabolic Control of Glycosylation Forms for Establishing Glycan-Dependent Protein Interaction Networks November 18, 2024
Protein-protein interactions (PPIs) provide essential insights into the complex molecular mechanisms and signaling pathways within cells that regulate development and disease-related phenotypes. However, for membrane proteins, the impact of various forms of glycosylation has often been overlooked in PPI studies. In this study, we introduce a novel approach, glycan-dependent affinity purification followed by mass spectrometry […]
Optimized and Robust Workflow for Quantifying the Canonical Histone Ubiquitination Marks H2AK119ub and H2BK120ub by LC-MS/MS November 18, 2024
The eukaryotic genome is packaged around histone proteins, which are subject to a myriad of post-translational modifications. By controlling DNA accessibility and the recruitment of protein complexes that mediate chromatin-related processes, these modifications constitute a key mechanism of epigenetic regulation. Since mass spectrometry can easily distinguish between these different modifications, it has become an essential […]
On the Hunt for the Histone Code November 3, 2024
Our genome is not made of naked DNA but a fiber (chromatin) composed of DNA and proteins packaged into our chromosomes. The basic building block of chromatin is the nucleosome, which has two copies of each of the proteins called histones (H2A, H2B, H3, and H4) wrapped by 146 base pairs of DNA. Regions of […]
A proteogenomic surfaceome study identifies DLK1 as an immunotherapeutic target in neuroblastoma October 25, 2024
Cancer immunotherapies produce remarkable results in B cell malignancies; however, optimal cell surface targets for many solid cancers remain elusive. Here, we present an integrative proteomic, transcriptomic, and epigenomic analysis of tumor and normal tissues to identify biologically relevant cell surface immunotherapeutic targets for neuroblastoma, an often-fatal childhood cancer. Proteogenomic analyses reveal sixty high-confidence candidate […]
Author Correction: Cancer-associated Histone H3 N-terminal arginine mutations disrupt PRC2 activity and impair differentiation October 22, 2024
No abstract
Online, Bottom-up Characterization of Histone H4 4-17 Isomers October 18, 2024
The "Histone Code" is comprised of specific types and positions of post-translational modifications (PTMs) which produce biological signals for gene regulation and have potential as biomarkers for medical diagnostics. Previous work has shown that electron-based fragmentation improves the sequence coverage and confidence of labile PTM position assignment. Here, we evaluated two derivatization methods (e.g., irreversible […]
Systematic perturbations of SETD2, NSD1, NSD2, NSD3, and ASH1L reveal their distinct contributions to H3K36 methylation October 10, 2024
CONCLUSIONS: Within genes, SETD2 primarily deposits H3K36me3, while the other K36MTs deposit H3K36me1/2 independently of SETD2 activity. For the deposition of H3K36me1/2, we find a hierarchy of K36MT activities where NSD1 > NSD2 > NSD3 > ASH1L. While NSD1 and NSD2 are responsible for most genome-wide propagation of H3K36me2, the activities of NSD3 and ASH1L […]
A circular engineered sortase for interrogating histone H3 in chromatin October 7, 2024
Reversible modification of the histone H3 N-terminal tail is critical in regulating chromatin structure, gene expression, and cell states, while its dysregulation contributes to disease pathogenesis. Understanding the crosstalk between H3 tail modifications in nucleosomes constitutes a central challenge in epigenetics. Here we describe an engineered sortase transpeptidase, cW11, that displays highly favorable properties for […]

News in 2022

December 2022

Ben is re-elected to the HUPO Governing Council as a Western region representative (https://hupo.org/Governance).

Peder’s research on understanding the role of microbe metabolism on histone acetylation and gene expression is published in Cell Reports!

November 2022

Axe is awarded a BMB Department Elson Fellowship for outstanding contributions in the areas of teaching, scholarship, collegiality and citizenship within the department.

Ben is a named a Highly Cited Researcher by Clarivate.

October 2022

Ben is named the Best Latinx Head and Chair award winner from Inaugural Vanderbilt Basic Sciences’ Hispanic and Latin Heritage Month.

July 2022

The lab says goodbye to postdoc Peder Lund who will start his own lab at the Case Western Reserve School of Medicine.

May 2022

Two publications from the lab to detail new MS approaches for RNA modification analysis are published in JASMS and Analytical Chemistry, respectively.

March 2022

The Garcia lab moves into their new lab space in the South Building.

Publications in 2022

Combinatorial Histone H3 Modifications Are Dynamically Altered in Distinct Cell Cycle Phases

Combinatorial Histone H3 Modifications Are Dynamically Altered in Distinct Cell Cycle Phases. Lu C, Coradin M, Janssen KA, Sidoli S, Garcia BA. J Am Soc Mass Spectrom. 2021 Apr 5. doi: 10.1021/jasms.0c00451.

Structure of TFIIK for phosphorylation of CTD of RNA polymerase II

Structure of TFIIK for phosphorylation of CTD of RNA polymerase II. van Eeuwen T, Li T, Kim HJ, Gorbea Colón JJ, Parker MI, Dunbrack RL, Garcia BA, Tsai KL, Murakami K. Sci Adv. 2021 Apr 7;7(15):eabd4420.

Sex-specific effects of in vitro fertilization on adult metabolic outcomes and hepatic transcriptome and proteome in mouse

Sex-specific effects of in vitro fertilization on adult metabolic outcomes and hepatic transcriptome and proteome in mouse. Narapareddy L, Rhon-Calderon EA, Vrooman LA, Baeza J, Nguyen DK, Mesaros C, Lan Y, Garcia BA, Schultz RM, Bartolomei MS. FASEB J. 2021 Apr;35(4):e21523.

Improved SILAC Quantification with Data-Independent Acquisition to Investigate Bortezomib-Induced Protein Degradation

Improved SILAC Quantification with Data-Independent Acquisition to Investigate Bortezomib-Induced Protein Degradation. Pino LK, Baeza J, Lauman R, Schilling B, Garcia BA. J Proteome Res. 2021 Apr 2;20(4):1918-1927.

An Esrrb and Nanog Cell Fate Regulatory Module Controlled by Feed Forward Loop Interactions

An Esrrb and Nanog Cell Fate Regulatory Module Controlled by Feed Forward Loop Interactions. Sevilla A, Papatsenko D, Mazloom AR, Xu H, Vasileva A, Unwin RD, LeRoy G, Chen EY, Garrett-Bakelman FE, Lee DF, Trinite B, Webb RL, Wang Z, Su J, Gingold J, Melnick A, Garcia BA, Whetton AD, MacArthur BD, Ma’ayan A, Lemischka IR. Front Cell Dev Biol. 2021 Mar 19;9:630067.

Long-term behavioral and cell-type-specific molecular effects of early life stress are mediated by H3K79me2 dynamics in medium spiny neurons

Long-term behavioral and cell-type-specific molecular effects of early life stress are mediated by H3K79me2 dynamics in medium spiny neurons. Kronman H, Torres-Berrío A, Sidoli S, Issler O, Godino A, Ramakrishnan A, Mews P, Lardner CK, Parise EM, Walker DM, van der Zee YY, Browne CJ, Boyce BF, Neve R, Garcia BA, Shen L, Peña CJ, Nestler EJ. Nat Neurosci. 2021 Mar 15. doi: 10.1038/s41593-021-00814-8. Online ahead of print.

Chromatin dysregulation associated with NSD1 mutation in head and neck squamous cell carcinoma

Chromatin dysregulation associated with NSD1 mutation in head and neck squamous cell carcinoma. Farhangdoost N, Horth C, Hu B, Bareke E, Chen X, Li Y, Coradin M, Garcia BA, Lu C, Majewski J. Cell Rep. 2021 Feb 23;34(8):108769.

Histone Modifications in Papillomavirus Virion Minichromosomes

Histone Modifications in Papillomavirus Virion Minichromosomes. Porter SS, Liddle JC, Browne K, Pastrana DV, Garcia BA, Buck CB, Weitzman MD, McBride AA. mBio. 2021 Feb 16;12(1):e03274-20.

Cryo-EM structures of engineered active bc1-cbb3 type CIII2CIV super-complexes and electronic communication between the complexes

Cryo-EM structures of engineered active bc₁-cbb₃ type CIII₂CIV super-complexes and electronic communication between the complexes. Steimle S, van Eeuwen T, Ozturk Y, Kim HJ, Braitbard M, Selamoglu N, Garcia BA, Schneidman-Duhovny D, Murakami K, Daldal F. Nat Commun. 2021 Feb 10;12(1):929.

Enhancing Open Modification Searches via a Combined Approach Facilitated by Ursgal

Enhancing Open Modification Searches via a Combined Approach Facilitated by Ursgal. Schulze S, Igiraneza AB, Kösters M, Leufken J, Leidel SA, Garcia BA, Fufezan C, Pohlschroder M. J Proteome Res. 2021 Apr 2;20(4):1986-1996.

HDAC inhibition results in widespread alteration of the histone acetylation landscape and BRD4 targeting to gene bodies

HDAC inhibition results in widespread alteration of the histone acetylation landscape and BRD4 targeting to gene bodies. Slaughter MJ, Shanle EK, Khan A, Chua KF, Hong T, Boxer LD, Allis CD, Josefowicz SZ, Garcia BA, Rothbart SB, Strahl BD, Davis IJ. Cell Rep. 2021 Jan 19;34(3):108638.

Comparative proteomics identifies Schlafen 5 (SLFN5) as a herpes simplex virus restriction factor that suppresses viral transcription

Structure and noncanonical Cdk8 activation mechanism within an Argonaute-containing Mediator kinase module

Structure and noncanonical Cdk8 activation mechanism within an Argonaute-containing Mediator kinase module.

Li YC, Chao TC, Kim HJ, Cholko T, Chen SF, Li G, Snyder L, Nakanishi K, Chang CE, Murakami K, Garcia BA, Boyer TG, Tsai KL. Sci Adv. 2021 Jan 15;7(3):eabd4484.