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Recent publications from the IIHG Bioinformatics Division

Upregulation of fatty acid synthesis genes in the livers of adolescent female rats caused by inhalation exposure to PCB52 (2,2',5,5'-Tetrachlorobiphenyl)

Saturday, July 27, 2024
Brynn Kyleakin Helm-Kwasny
Elevated airborne PCB levels in older schools are concerning due to their health impacts, including cancer, metabolic dysfunction-associated steatotic liver disease (MASLD), cardiovascular issues, neurodevelopmental diseases, and diabetes. During a four-week inhalation exposure to PCB52, an air pollutant commonly found in school environments, adolescent rats exhibited notable presence of PCB52 and its hydroxylated forms in their livers, alongside changes in gene expression. Female rats exhibited...

Development of a humanized anti-FABP4 monoclonal antibody for potential treatment of breast cancer

Thursday, July 25, 2024
Jiaqing Hao
CONCLUSIONS: Our current evidence suggests that targeting FABP4 with humanized monoclonal antibodies may represent a novel strategy for the treatment of breast cancer and possibly other obesity- associated diseases.

FABP4-mediated lipid accumulation and lipolysis in tumor associated macrophages promote breast cancer metastasis

Monday, July 15, 2024
Matthew Yorek
A high density of tumor-associated macrophages (TAMs) is associated with poorer prognosis and survival in breast cancer patients. Recent studies have shown that lipid accumulation in TAMs can promote tumor growth and metastasis in various models. However, the specific molecular mechanisms that drive lipid accumulation and tumor progression in TAMs remain largely unknown. Herein, we demonstrated that unsaturated fatty acids (FAs), unlike saturated ones, are more likely to form lipid droplets in...

Modulation of the Immunological Milieu in Acute Aneurysmal Subarachnoid Hemorrhage: The Potential Role of Monocytes Through CXCL10 Secretion

Thursday, May 23, 2024
Sebastian Sanchez
Emerging evidence indicates that aneurysmal subarachnoid hemorrhage (aSAH) elicits a response from both innate and adaptive immune systems. An upregulation of CD8 + CD161 + cells has been observed in the cerebrospinal fluid (CSF) after aSAH, yet the precise role of these cells in the context of aSAH is unkown. CSF samples from patients with aSAH and non-aneurysmal SAH (naSAH) were analyzed. Single-cell RNA sequencing (scRNAseq) was performed on CD8 + CD161 + sorted samples from aSAH patients....

The natural history and genotype-phenotype correlations of TMPRSS3 hearing loss: an international, multi-center, cohort analysis

Wednesday, May 1, 2024
Brett M Colbert
TMPRSS3-related hearing loss presents challenges in correlating genotypic variants with clinical phenotypes due to the small sample sizes of previous studies. We conducted a cross-sectional genomics study coupled with retrospective clinical phenotype analysis on 127 individuals. These individuals were from 16 academic medical centers across 6 countries. Key findings revealed 47 unique TMPRSS3 variants with significant differences in hearing thresholds between those with missense variants versus...

Krüppel-like factor 4 in transcriptional control of the three unique isoforms of Agouti-related peptide in mice

Monday, December 25, 2023
McKenzie L Ritter
Agouti-related peptide (AgRP/Agrp) within the hypothalamic arcuate nucleus (ARC) contributes to the control of energy balance, and dysregulated Agrp may contribute to metabolic adaptation during prolonged obesity. In mice, three isoforms of Agrp are encoded via distinct first exons. Agrp-A (ENSMUST00000005849.11) contributed 95% of total Agrp in mouse ARC, whereas Agrp-B (ENSMUST00000194654.2) dominated in placenta (73%). Conditional deletion of Klf4 from Agrp-expressing cells (Klf4^(Agrp)^(-KO)...

Keratinocyte FABP5-VCP complex mediates recruitment of neutrophils in psoriasis

Wednesday, November 15, 2023
Jiaqing Hao
One of the hallmarks of intractable psoriasis is neutrophil infiltration in skin lesions. However, detailed molecular mechanisms of neutrophil chemotaxis and activation remain unclear. Here, we demonstrate a significant upregulation of epidermal fatty acid binding protein (E-FABP, FABP5) in the skin of human psoriasis and psoriatic mouse models. Genetic deletion of FABP5 in mice by global knockout and keratinocyte conditional (Krt6a-Cre) knockout, but not myeloid cell conditional (LysM-Cre)...

Full bibliography

Tollefson, M.R., Gogal, R.A., Weaver, A.M. et al. Assessing variants of uncertain significance implicated in hearing loss using a comprehensive deafness proteome. Hum Genet 142, 819–834 (2023). https://doi.org/10.1007/s00439-023-02559-9

Jehan Alladina, et al.  A human model of asthma exacerbation reveals transcriptional programs and cell circuits specific to allergic asthma. Sci. Immunol.8, eabq6352 (2023). DOI:10.1126/sciimmunol.abq6352

Ganesh, V.; Seol, D.; Gomez-Contreras, P.C.; Keen, H.L.; Shin, K.; Martin, J.A. Exosome-Based Cell Homing and Angiogenic Differentiation for Dental Pulp Regeneration. Int. J. Mol. Sci. 2023, 24, 466. https://doi.org/10.3390/ijms24010466

G. Graham, M.S. Chimenti, K.L. Knudtson, D.N. Grenard, L. Co, M. Sumner, T. Tchou, K.M. Bieszczad.  Learning induces unique transcriptional landscapes in the auditory cortex. bioRxiv 2023.04.15.536914;  doi:  https://doi.org/10.1101/2023.04.15.536914 (This article is a preprint and has not been peer reviewed) 


Brittany P. Todd, Zili Luo, Noah Gilkes, Michael S. Chimenti, Zeru Peterson, Madison Mix, John T. Harty, Thomas Nickl-Jockschat, Polly J. Ferguson, Alexander G. Bassuk, Elizabeth A. Newell.  Selective neuroimmune modulation by type I interferon drives neuropathology and neurologic dysfunction following traumatic brain injury. bioRxiv 2023.06.06.543774; doi: https://doi.org/10.1101/2023.06.06.543774

Joseph B. Lesnak, Kazuhiro Hayashi, Ashley N. Plumb, Adam J. Janowski, Michael S. Chimenti, Kathleen A. Sluka.  The impact of sex and physical activity on the local immune response to muscle pain. Brain, Behavior, and Immunity, Volume 111, 2023, Pages 4-20, ISSN 0889-1591, https://doi.org/10.1016/j.bbi.2023.03.020.

Francoise A. Gourronc, Michael S. Chimenti, Hans-Joachim Lehmler, James A. Ankrum, Aloysius J. Klingelhutz.  Hydroxylation markedly alters how the polychlorinated biphenyl (PCB) congener, PCB52, affects gene expression in human preadipocytes. Toxicology in Vitro,Volume 89,2023,105568,ISSN 0887-2333,https://doi.org/10.1016/j.tiv.2023.105568.

Francoise A. Gourronc, Brynn K. Helm, Larry W. Robertson, Michael S. Chimenti, Hans Joachim-Lehmler, James A. Ankrum, Aloysius J. Klingelhutz. Transcriptome sequencing of 3,3′,4,4′,5-Pentachlorobiphenyl (PCB126)-treated human preadipocytes demonstrates progressive changes in pathways associated with inflammation and diabetes. Toxicology in Vitro,Volume 83,2022,105396,ISSN 0887-2333,https://doi.org/10.1016/j.tiv.2022.105396.

Nawu Yang, Jevan Christie, Henry L. Keen, Maurice A. Matthew, Chaoqun Yao. Draft Genome Sequence of Trichomonas tenax Strain Hs-4:NIH.  Microbiology Resource Announcements.  doi:10.1128/mra.00157-22. 
https://journals.asm.org/doi/abs/10.1128/mra.00157-22

Miles J. Klimara, Carla Nishimura, Donghong Wang, Diana L. Kolbe, Amanda M. Schaefer, William D. Walls, Kathy L. Frees, Richard J.H. Smith, Hela Azaiez. De novo variants are a common cause of genetic hearing loss. Genetics in Medicine. Volume 24, Issue 12, 2022, Pages 2555-2567, ISSN 1098-3600, https://doi.org/10.1016/j.gim.2022.08.028.

Athmane Teghanemt, Priyanjali Pulipati, Kenneth Day, Matt Yorek, Ren Yi, Kara Misel-Wuchter, Henry L Keen, Christy Au, Thorsten Maretzky, Prajwal Gurung, Dan R. Littman, Priya D. Issuree. Epigenetic Programming during thymic development sets the stage for optimal function in effector T cells via DNA demethylation.  bioRxiv 2021.05.03.442517; doi: https://doi.org/10.1101/2021.05.03.442517

Teghanemt, A., Pulipati, P., Misel-Wuchter, K., Keen, HL., et al. CD4 expression in effector T cells depends on DNA demethylation over a developmentally established stimulus-responsive element. Nature  Communication 13, 1477 (2022). https://doi.org/10.1038/s41467-022-28914-4

Joseph Lesnak, Kazuhiro Hayashi, Ashley Plumb, Michael S. Chimenti, Kathleen A. Sluka.  RNA Sequencing Reveals Transcriptional Changes in Muscle Tissue in Response to Muscle Pain in Exercised and Sedentary Mice. The Journal of Pain, Volume 23, Issue 5, Supplement, 2022, Page 38, ISSN 1526-5900, https://doi.org/10.1016/j.jpain.2022.03.146.

Seligman, K. L., Shearer, A. E., Frees, K., Nishimura, C., Kolbe, D., Dunn, C., Hansen, M. R., Gantz, B. J., & Smith, R. J. H. (2022). Genetic Causes of Hearing Loss in a Large Cohort of Cochlear Implant Recipients. Otolaryngology–Head and Neck Surgery, 166(4), 734–737. https://doi.org/10.1177/01945998211021308

Hirsch, Y., Tangshewinsirikul, C., Booth, K.T. et al. A synonymous variant in MYO15A enriched in the Ashkenazi Jewish population causes autosomal recessive hearing loss due to abnormal splicing. Eur J Hum Genet 29, 988–997 (2021). https://doi.org/10.1038/s41431-020-00790-w

Todd, B.P., Chimenti, M.S., Luo, Z. et al. Traumatic brain injury results in unique microglial and astrocyte transcriptomes enriched for type I interferon response. J Neuroinflammation 18, 151 (2021). https://doi.org/10.1186/s12974-021-02197-w

Derek Simonsen, Nicole Cady, Chunyun Zhang, Rachel L Shrode, Michael L McCormick, Douglas R Spitz, Michael S Chimenti, Kai Wang, Ashutosh Mangalam, Hans-Joachim Lehmler, The Effects of Benoxacor on the Liver and Gut Microbiome of C57BL/6 Mice, Toxicological Sciences, Volume 186, Issue 1, March 2022, Pages 102–117, https://doi.org/10.1093/toxsci/kfab142

Ratcliff J, Thurman A (2020). aggregateBioVar: Differential Gene Expression Analysis for Multi-subject scRNA-seq. R package version 1.0.0,  https://academic.oup.com/bioinformatics/advance-article/doi/10.1093/bioinformatics/btab337/6273181

Wang, Zhaoming; Chimenti, Michael S; Strouse, Christopher; Weiner, George J."T cells, particularly activated CD4+ cells, maintain anti-CD20-mediated NK cell viability and antibody dependent cellular cytotoxicity."  Cancer Immunology, Immunotherapy.  1-13, 2021. Springer Berlin Heidelberg.

Sabree, Shakoora A; Voigt, Andrew P; Blackwell, Sue E; Vishwakarma, Ajaykumar; Chimenti, Michael S; Salem, Aliasger K; Weiner, George J. "Direct and indirect immune effects of CMP-001, a virus-like particle containing a TLR9 agonist."  Journal for Immunotherapy of Cancer.  9:6. 2021. BMJ Publishing Group.

Thurman, Andrew L; Ratcliff, Jason A; Chimenti, Michael S; Pezzulo, Alejandro A. "Differential gene expression analysis for multi-subject single cell RNA sequencing studies with aggregateBioVar" BMC Bioinformatics. 2021. 

Allred, Merri-Grace; Chimenti, Michael S; Ciecko, Ashley E; Chen, Yi-Guang; Lieberman, Scott M. "Characterization of Type I Interferon-Associated Chemokines and Cytokines in Lacrimal Glands of Nonobese Diabetic Mice" International Journal of Molecular Sciences. 22:7. 3767. 2021.

Merritt, Nicole; Garcia, Keith; Rajendran, Dushyandi; Lin, Zhen-Yuan; Zhang, Xiaomeng; Mitchell, Katrina A; Borcherding, Nicholas; Fullenkamp, Colleen; Chimenti, Michael S; Gingras, Anne-Claude. "TAZ-CAMTA1 and YAP-TFE3 alter the TAZ/YAP transcriptome by recruiting the ATAC histone acetyltransferase complex" Elife, 10:e62857. 2021. eLife Sciences Publications Limited

Nicole Merritt, Keith Garcia, Dushyandi Rajendran, Zhen-Yuan Lin, Xiaomeng Zhang, Katrina M. Mitchell,  Nicholas Borcherding,  Colleen Fullenkamp, Michael Chimenti, Anne-Claude Gingras, Kieran F. Harvey, Munir R. Tanas.  TAZ-CAMTA1 and YAP-TFE3 modulate the basal TAZ/YAP transcriptional program by recruiting the ATAC histone acetyltransferase complex. bioRxiv 2020.09.07.286633; doi: https://doi.org/10.1101/2020.09.07.286633

Kumuthini J, Chimenti M, Nahnsen S, Peltzer A, Meraba R, et al. (2020) Ten simple rules for providing effective bioinformatics research support. PLOS Computational Biology 16(3): e1007531. https://doi.org/10.1371/journal.pcbi.1007531

Oliver W. Gramlich, Alexander J. Brown, Cheyanne R. Godwin, Michael S. Chimenti, Lauren K. Boland, James A. Ankrum, Randy H. Kardon; Systemic Mesenchymal Stem Cell Treatment Mitigates Structural and Functional Retinal Ganglion Cell Degeneration in a Mouse Model of Multiple Sclerosis. Trans. Vis. Sci. Tech. 2020;9(8):16. doi: https://doi.org/10.1167/tvst.9.8.16.

Heather A Stiff, Christina M Sloan-Heggen, Ashley Ko, Wanda L Pfeifer, Diana L Kolbe, Carla J Nishimura, Kathy L Frees, Kevin T Booth, Donghong Wang, Amy E Weaver, Hela Azaiez, John Kamholz, Richard J H Smith, Arlene V Drack. Is it Usher syndrome? Collaborative diagnosis and molecular genetics of patients with visual impairment and hearing loss. Ophthalmic Genet 2020 Apr;41(2):151-158. doi: 10.1080/13816810.2020.1747088. Epub 2020 Apr 13.

 
W Daniel Walls, Hideaki Moteki, Taylor R Thomas, Shin-Ya Nishio, Hidekane Yoshimura, Yoichiro Iwasa, Kathy L Frees, Carla J Nishimura, Hela Azaiez, Kevin T Booth, Robert J Marini, Diana L Kolbe, A Monique Weaver, Amanda M Schaefer, Kai Wang, Terry A Braun, Shin-Ichi Usami, Peter G Barr-Gillespie, Guy P Richardson, Richard J Smith, Thomas L Casavant. A comparative analysis of genetic hearing loss phenotypes in European/American and Japanese populations.  Hum Genet 2020 Oct;139(10):1315-1323. doi: 10.1007/s00439-020-02174-y. Epub 2020 May 7.

Ajaykumar Vishwakarma, Nicholas Bocherding, Michael S. Chimenti,  Purshottam Vishwakarma,  Kenneth Nepple,  Aliasger Salem,  Russell W. Jenkins,  Weizhou Zhang,  Yousef Zakharia.  Mapping the Immune Landscape of Clear Cell Renal Cell Carcinoma by Single-Cell RNA-seq. bioRxiv 824482; https://doi.org/10.1101/824482. 

Sara B. Mitchell, Michael S. Chimenti, Hiroyuki Kawano, Tsun Ming Tom Yuen, Ashley E. Sjurson, Sadahiro Iwabuchi, Kevin L Knudtson, Thomas B Bair, Diana Kolbe, N. Charles Harata.  Transcriptome profiles in brains of mice heterozygous for a DYT1 dystonia-associated mutation in the endogenous Tor1a gene.  bioRxiv 825505; doi: https://doi.org/10.1101/825505. 

Sophia C. Gaynor, Eric T. Monson, Marie E. Gaine, Michael S. Chimenti, Rachel D. Reichman, Meredith Parsons, Lalita Oonthonpan, Peter P. Zandi, James B. Potash, Virginia L. Willour. Male-specific association of the 2p25 region with suicide attempt in bipolar disorder.  Journal of Psychiatric Research, Volume 121, 2020, Pages 151-158.  https://doi.org/10.1016/j.jpsychires.2019.11.009.

Agbor LN, Nair AR, Wu J, Lu KT, Davis DR, Keen HL, Quelle FW, McCormick JA, Singer JD, Sigmund CD.  Conditional deletion of smooth muscle Cullin-3 causes severe progressive hypertension.  JCI Insight. 2019 Jun 11;5. pii: 129793.  https://doi.org/10.1172/jci.insight.129793

Black, EM, Chimenti, MS, Just, CL.  Metagenomic analysis of nitrogen‐cycling genes in upper Mississippi river sediment with mussel assemblages. MicrobiologyOpen 2019; 8:e739. https://doi.org/10.1002/mbo3.739

Mukohda M, Fang S, Wu J, Agbor LN, Nair AR, Ibeawuchi SC, Hu C, Liu X, Lu KT, Guo DF, Davis DR, Keen HL, Quelle FW, Sigmund CD. RhoBTB1 protects against hypertension and arterial stiffness by restraining phosphodiesterase 5 activity.  J Clin Invest. 2019 Mar 21;129(6):2318-2332. doi: https://doi.org/10.1172/JCI123462. 

Ranum PT, Goodwin AT, Yoshimura H, Kolbe DL, Walls WD, Koh JY, He DZZ, & Smith RJH.  Insights into the Biology of Hearing and Deafness Revealed by Single-Cell RNA Sequencing. Cell Rep. 2019 Mar 12;26(11):3160-3171.e3. doi: https://doi.org/10.1016/j.celrep.2019.02.053

Shearer AE, Frees K, Kolbe DL, Smith RJH. Comprehensive Genetic Testing for Deafness from Fresh and Archived Dried Blood Spots. Otolaryngol Head Neck Surg. 2018 Aug 28:194599818797291. doi: https://doi.org/10.1177/0194599818797291

Azaiez H, Booth KT, Ephraim SS, Crone B, Black-Ziegelbein EA, Marini RJ, Shearer AE, Sloan-Heggen CM, Kolbe D, Casavant T, Schnieders MJ, Nishimura C, Braun T, Smith RJH.  Genomic Landscape and Mutational Signatures of Deafness-Associated Genes. Am J Hum Genet. 2018 Oct 4;103(4):484-497. doi: https://doi.org/10.1016/j.ajhg.2018.08.006. Epub 2018 Sep 20.


Sandgren JA, Deng G, Linggonegoro DW, Scroggins SM, Perschbacher KJ, Nair AR, Nishimura TE, Zhang SY, Agbor LN, Wu J, Keen HL, Naber MC, Pearson NA, Zimmerman KA, Weiss RM, Bowdler NC, Usachev YM, Santillan DA, Potthoff MJ, Pierce GL, Gibson-Corley KN, Sigmund CD, Santillan MK, Grobe JL.  Arginine vasopressin infusion is sufficient to model clinical features of preeclampsia in mice.​  JCI Insight. 2018 Oct 4;3(19). pii: 99403. doi: https://doi.org/10.1172/jci.insight.99403. 

O'Brien, Kate M, Chimenti, Michael S, Farnell, Morgan, Tabler, Tom, Bair, Thomas, Bray, Joey L., Nonnenmann, Matthew W. High throughput genomic sequencing of bioaerosols in broiler chicken production facilities.  Microbial Biotechnology ( 2016) 9( 6), 782– 791 https://doi.org/10.1111/1751-7915.12380

Black EM, Chimenti MS, Just CL. 2017. Effect of freshwater mussels on the vertical distribution of anaerobic ammonia oxidizers and other nitrogen-transforming microorganisms in upper Mississippi river sediment. PeerJ 5:e3536 https://doi.org/10.7717/peerj.3536


Sarah von Spiczak, Katherine L. Helbig, Deepali N. Shinde, Robert Huether, ..., Diana L. Kolbe, Georgie Hollingsworth, Bernd A. Neubauer, Hiltrud Muhle, Ulrich Stephani, Ingrid E. Scheffer, Sérgio D.J. Pena, Sanjay M. Sisodiya, Ingo Helbig.  DNM1 encephalopathy.  For the Epi4K Consortium, For the EuroEPINOMICS-RES NLES Working Group.  Neurology Jul 2017, 89 (4) 385-394; DOI: https://doi.org/10.1212/WNL.0000000000004152

Moteki, H., Azaiez, H., Sloan-Heggen, C. M., Booth, K., Nishio, S., Wakui, K., Kolbe, D, … Usami, S. (2016). Detection and Confirmation of Deafness-Causing Copy Number Variations in the STRC Gene by Massively Parallel Sequencing and Comparative Genomic Hybridization. Annals of Otology, Rhinology & Laryngology, 125(11), 918–923. https://doi.org/10.1177/0003489416661345

Julie Wertz, Qianli Liao, Thomas B Bair & Michael S Chimenti.  PyVar: An Extensible Framework for Variant Annotator Comparison. bioRxiv 078386; doi: https://doi.org/10.1101/078386