Genes & Human Disease Research Program

The human genome is composed of more than 3 billion nucleotides that essentially functions as a molecular hard drive that stores all the information needed for how the cells in our body function. Of the 3 billion nucleotides, roughly 2% encodes for the different proteins that perform the various cellular functions needed for life. The remaining 98% of the human genome regulates what, when, and how each gene is expressed during the life of a cell. The random inheritance of different variations of the DNA sequences of encoded genes and non-protein coding regulatory regions from a person’s parents provides, in many ways, the characteristics that make each individual unique. Unfortunately, inheritance of genetic variations also increases a person’s risk of developing different human diseases.

The Genes and Human Disease Research Program focuses on identifying and understanding how genetic variations cause human diseases. While our investigators share this focus, each has their own specific interests including determining the function of non-coding RNA, and understanding how the complex 3D organization of the genome, disease-associated non-coding variants, and the epigenome regulate gene expression in health and disease. In addition, our faculty are developing and applying new machine and deep-learning approaches to identify new disease-associated genetic variations and define disease-associated gene networks.

The Genes and Human Disease Research Program works closely with the OMRF CLIA certified Clinical Genomics Center, the OMRF CAP-accredited Biorepository and the OMRF Quantitative Analysis Core. These Cores were established using funding from various grants through the NIH Institutional Development Award (IDeA) program, and continue to be supported by the OMRF. Our investigators benefit from the state-of-the-art sequencing technologies, sample procurement, processing and storage, and data analysis expertise afforded by these Cores.

2020

Forsthoefel DJ, Cejda NI, Khan UW, Newmark PA. Cell-type diversity and regionalized gene expression in the planarian intestine. Elife 9, 2020 April, PMID: 32240093, PMCID: PMC7117911

Garman L, Pezant N, Pastori A, Savoy KA, Li C, Levin AM, Iannuzzi MC, Rybicki BA, Adrianto I, Montgomery CG. Genome-Wide Association Study of Ocular Sarcoidosis Confirms HLA Associations and Implicates Barrier Function and Autoimmunity in African Americans. Ocul Immunol Inflamm:1-6, 2020 March, PMID: 32141793

Kiss T, Nyúl-Tóth Á, Balasubramanian P, Tarantini S, Ahire C, Yabluchanskiy A, Csipo T, Farkas E, Wren JD, Garman L, Csiszar A, Ungvari Z. Nicotinamide mononucleotide (NMN) supplementation promotes neurovascular rejuvenation in aged mice: transcriptional footprint of SIRT1 activation, mitochondrial protection, anti-inflammatory, and anti-apoptotic effects. Geroscience, 2020 February, PMID: 32056076, PMCID: PMC7206476

Kiss T, Tarantini S, Csipo T, Balasubramanian P, Nyúl-Tóth Á, Yabluchanskiy A, Wren JD, Garman L, Huffman DM, Csiszar A, Ungvari Z. Circulating anti-geronic factors from heterochonic parabionts promote vascular rejuvenation in aged mice: transcriptional footprint of mitochondrial protection, attenuation of oxidative stress, and rescue of endothelial function by young blood. Geroscience, 2020 March, PMID: 32172434, PMCID: PMC7205954

Medley SC, Rathnakar BH, Georgescu C, Wren JD, Olson LE. Fibroblast-specific Stat1 deletion enhances the myofibroblast phenotype during tissue repair. Wound Repair Regen, 2020 March, PMID: 32175700

Petree C, Varshney GK. MultiFRAGing: Rapid and Simultaneous Genotyping of Multiple Alleles in a Single Reaction. Sci Rep 10:3172, 2020 February, PMID: 32081936, PMCID: PMC7035419

Ray-Jones H, Duffus K, McGovern A, Martin P, Shi C, Hankinson J, Gough O, Yarwood A, Morris AP, Adamson A, Taylor C, Ding J, Gaddi VP, Fu Y, Gaffney P, Orozco G, Warren RB, Eyre S. Mapping DNA interaction landscapes in psoriasis susceptibility loci highlights KLF4 as a target gene in 9q31. BMC Biol 18:47, 2020 May, PMID: 32366252, PMCID: PMC7199343

Sapkota H, Wren JD, Gorbsky GJ. Chondrosarcoma-associated gene 1 (CSAG1) maintains the integrity of the mitotic centrosome in cells with defective p53. J Cell Sci, 2020 April, PMID: 32295846

Sataranatarajan K, Pharaoh G, Brown JL, Ranjit R, Piekarz KM, Street K, Wren JD, Georgescu C, Kinter C, Kinter M, Freeman WM, Richardson A, Van Remmen H. Molecular changes in transcription and metabolic pathways underlying muscle atrophy in the CuZnSOD null mouse model of sarcopenia. Geroscience, 2020 May, PMID: 32394347

Vona B, Doll J, Hofrichter MAH, Haaf T, Varshney GK. Small fish, big prospects: using zebrafish to unravel the mechanisms of hereditary hearing loss. Hear Res:107906, 2020 February, PMID: 32063424

2019

Acevedo-Canabal A, Colón-Cruz L, Rodriguez-Morales R, Varshney GK, Burgess S, González-Sepúlveda L, Yudowski G, Behra M. Altered Swimming Behaviors in Zebrafish Larvae Lacking Cannabinoid Receptor 2. Cannabis Cannabinoid Res 4:88-101, 2019 June, PMID: 31236475, PMCID: PMC6590727

Ahn B, Ranjit R, Premkumar P, Pharaoh G, Piekarz KM, Matsuzaki S, Claflin DR, Riddle K, Judge J, Bhaskaran S, Satara Natarajan K, Barboza E, Wronowski B, Kinter M, Humphries KM, Griffin TM, Freeman WM, Richardson A, Brooks SV, Van Remmen H. Mitochondrial oxidative stress impairs contractile function but paradoxically increases muscle mass via fibre branching. J Cachexia Sarcopenia Muscle 10:411-428, 2019 April, PMID: 30706998, PMCID: PMC6463475

Bagavant H, Dunkleberger ML, Wolska N, Sroka M, Rasmussen A, Adrianto I, Montgomery C, Sivils K, Guthridge JM, James JA, Merrill JT, Deshmukh US. Antibodies to periodontogenic bacteria are associated with higher disease activity in lupus patients. Clin Exp Rheumatol 37:106-111, 2019 January, PMID: 29998833, PMCID: PMC6309750

Barnett AG, Wren JD. Examination of CIs in health and medical journals from 1976 to 2019: an observational study. BMJ Open 9:e032506, 2019 November, PMID: 31753893, PMCID: PMC6887056

Chen Y, Adrianto I, Ianuzzi MC, Garman L, Montgomery CG, Rybicki BA, Levin AM, Li J. Extended methods for gene-environment-wide interaction scans in studies of admixed individuals with varying degrees of relationships. Genet Epidemiol, 2019 February, PMID: 30793815, PMCID: PMC6648658

Georgescu C, Corbin JM, Thibivilliers S, Webb ZD, Zhao YD, Koster J, Fung KM, Asch AS, Wren JD, Ruiz-Echevarría MJ. A TMEFF2-regulated cell cycle derived gene signature is prognostic of recurrence risk in prostate cancer. BMC Cancer 19:423, 2019 May, PMID: 31060542, PMCID: PMC6503380

Harris VM, Koelsch KA, Kurien BT, Harley ITW, Wren JD, Harley JB, Scofield RH. Characterization of cxorf21 Provides Molecular Insight Into Female-Bias Immune Response in SLE Pathogenesis. Front Immunol 10:2160, 2019 October, PMID: 31695690, PMCID: PMC6816314

James JA, Chen H, Young KA, Bemis EA, Seifert J, Bourn RL, Deane KD, Demoruelle MK, Feser M, O'Dell JR, Weisman MH, Keating RM, Gaffney PM, Kelly JA, Langefeld CD, Harley JB, Robinson W, Hafler DA, O'Connor KC, Buckner J, Guthridge JM, Norris JM, Holers VM. Latent autoimmunity across disease-specific boundaries in at-risk first-degree relatives of SLE and RA patients. EBioMedicine, 2019 April, PMID: 30952617, PMCID: PMC6491794

Jog NR, Young KA, Munroe ME, Harmon MT, Guthridge JM, Kelly JA, Kamen DL, Gilkeson GS, Weisman MH, Karp DR, Gaffney PM, Harley JB, Wallace DJ, Norris JM, James JA. Association of Epstein-Barr virus serological reactivation with transitioning to systemic lupus erythematosus in at-risk individuals. Ann Rheum Dis, 2019 June, PMID: 31217170, PMCID: PMC6692217

Keihani S, Kluever V, Mandad S, Bansal V, Rahman R, Fritsch E, Gomes LC, Gärtner A, Kügler S, Urlaub H, Wren JD, Bonn S, Rizzoli SO, Fornasiero EF. The long noncoding RNA neuroLNC regulates presynaptic activity by interacting with the neurodegeneration-associated protein TDP-43. Sci Adv 5:eaay2670, 2019 December, PMID: 31897430, PMCID: PMC6920028

Kinney N, Titus-Glover K, Wren JD, Varghese RT, Michalak P, Liao H, Anandakrishnan R, Pulenthiran A, Kang L, Garner HR. CAGm: a repository of germline microsatellite variations in the 1000 genomes project. Nucleic Acids Res 47:D39-D45, 2019 January, PMID: 30329086, PMCID: PMC6323891

Kiss T, Giles CB, Tarantini S, Yabluchanskiy A, Balasubramanian P, Gautam T, Csipo T, Nyúl-Tóth Á, Lipecz A, Szabo C, Farkas E, Wren JD, Csiszar A, Ungvari Z. Nicotinamide mononucleotide (NMN) supplementation promotes anti-aging miRNA expression profile in the aorta of aged mice, predicting epigenetic rejuvenation and anti-atherogenic effects. Geroscience, 2019 August, PMID: 31463647, PMCID: PMC6815288

Kottyan LC, Maddox A, Braxton JR, Stucke EM, Mukkada V, Putnam PE, Abonia JP, Chehade M, Wood RA, Pesek RD, Vickery BP, Furuta GT, Dawson P, Sampson HA, Martin LJ, Kelly JA, Kimberly RP, Sivils K, Gaffney PM, Kaufman K, Harley JB, Rothenberg ME. Genetic variants at the 16p13 locus confer risk for eosinophilic esophagitis. Genes Immun 20:281-292, 2019 April, PMID: 29904099, PMCID: PMC6286696

Kowalski MH, Qian H, Hou Z, Rosen JD, Tapia AL, Shan Y, Jain D, Argos M, Arnett DK, Avery C, Barnes KC, Becker LC, Bien SA, Bis JC, Blangero J, Boerwinkle E, Bowden DW, Buyske S, Cai J, Cho MH, Choi SH, Choquet H, Cupples LA, Cushman M, Daya M, de Vries PS, Ellinor PT, Faraday N, Fornage M, Gabriel S, Ganesh SK, Graff M, Gupta N, He J, Heckbert SR, Hidalgo B, Hodonsky CJ, Irvin MR, Johnson AD, Jorgenson E, Kaplan R, Kardia SLR, Kelly TN, Kooperberg C, Lasky-Su JA, Loos RJF, Lubitz SA, Mathias RA, McHugh CP, Montgomery C, Moon JY, Morrison AC, Palmer ND, Pankratz N, Papanicolaou GJ, Peralta JM, Peyser PA, Rich SS, Rotter JI, Silverman EK, Smith JA, Smith NL, Taylor KD, Thornton TA, Tiwari HK, Tracy RP, Wang T, Weiss ST, Weng LC, Wiggins KL, Wilson JG, Yanek LR, Zöllner S, North KE, Auer PL, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium., TOPMed Hematology & Hemostasis Working Group., Raffield LM, Reiner AP, Li Y. Use of >100,000 NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium whole genome sequences improves imputation quality and detection of rare variant associations in admixed African and Hispanic/Latino populations. PLoS Genet 15:e1008500, 2019 December, PMID: 31869403, PMCID: PMC6953885

Liu K, Petree C, Requena T, Varshney P, Varshney GK. Expanding the CRISPR Toolbox in Zebrafish for Studying Development and Disease Front Cell Dev Biol:7:13, 2019 Mar, PMID: 30886848, PMCID: PMC6409501

Mahamud MR, Geng X, Ho YC, Cha B, Kim Y, Ma J, Chen L, Myers G, Camper S, Mustacich D, Witte M, Choi D, Hong YK, Chen H, Varshney G, Engel JD, Wang S, Kim TH, Lim KC, Srinivasan RS. GATA2 controls lymphatic endothelial cell junctional integrity and lymphovenous valve morphogenesis through miR-126. Development, 2019 October, PMID: 31582413, PMCID: PMC6857586

Miller BF, Pharaoh GA, Hamilton KL, Peelor FF, Kirkland JL, Freeman WM, Mann SN, Kinter M, Price JC, Stout MB. Short-term calorie restriction and 17α-estradiol administration elicit divergent effects on proteostatic processes and protein content in metabolically active tissues. J Gerontol A Biol Sci Med Sci, 2019 May, PMID: 31074767, PMCID: PMC7164531

Pasula S, Tessneer KL, Fu Y, Gopalakrishnan J, Pelikan RC, Kelly JA, Wiley GB, Wiley MM, Gaffney PM. Risk Variants with Opposing Functional Effects Result in Hypomorphic Expression of TNIP1 and Other Genes within a 3D Chromatin Network. Arthritis Rheumatol, 2019 December, PMID: 31804013, PMCID: PMC7188567

Perz AI, Giles CB, Brown CA, Porter H, Roopnarinesingh X, Wren JD. MNEMONIC: MetageNomic Experiment Mining to create an OTU Network of Inhabitant Correlations. BMC Bioinformatics 20:96, 2019 March, PMID: 30871469, PMCID: PMC6419333

Qian L, Bajana S, Georgescu C, Peng V, Wang HC, Adrianto I, Colonna M, Alberola-Ila J, Wren JD, Sun XH. Suppression of ILC2 differentiation from committed T cell precursors by E protein transcription factors. J Exp Med 216:884-899, 2019 April, PMID: 30898894, PMCID: PMC6446881

Rasmussen A, Stone DU, Kaufman CE, Hefner KS, Fram NR, Siatkowski RL, Huang AJW, Chodosh J, Rasmussen PT, Fife DA, Pezant N, Grundahl K, Radfar L, Lewis DM, Weisman MH, Venuturupalli S, Wallace DJ, Rhodus NL, Brennan MT, Montgomery CG, Lessard CJ, Scofield RH, Sivils KL. Reproducibility of Ocular Surface Staining in the Assessment of Sjögren Syndrome-Related Keratoconjunctivitis Sicca: Implications on Disease Classification. ACR Open Rheumatol 1:292-302, 2019 July, PMID: 31453437, PMCID: PMC6710016

Ratliff ML, Garton J, Garman L, Barron MD, Georgescu C, White KA, Chakravarty E, Wren JD, Montgomery CG, James JA, Webb CF. ARID3a gene profiles are strongly associated with human interferon alpha production. J Autoimmun 96:158-167, 2019 January, PMID: 30297159, PMCID: PMC6497177

Scofield RH, Sharma R, Pezant N, Kelly JA, Radfar L, Lewis DM, Kaufman CE, Cioli S, Harris J, Grundahl K, Rhodus NL, Wallace DJ, Weisman MH, Venuturupalli S, Brennan MT, Koelsch KA, Lessard CJ, Montgomery CG, Sivils KL, Rasmussen A. American Indians Have A Higher Risk Of Sjögren's Syndrome And More Disease Activity Than Caucasians And African-Americans. Arthritis Care Res (Hoboken), 2019 June, PMID: 31199565, PMCID: PMC6911033

Shah HB, Smith K, Wren JD, Webb CF, Ballard JD, Bourn RL, James JA, Lang ML. Insights From Analysis of Human Antigen-Specific Memory B Cell Repertoires. Front Immunol 9:3064, 2019 January, PMID: 30697210, PMCID: PMC6340933

Sharma R, Chaudhari KS, Kurien BT, Grundahl K, Radfar L, Lewis DM, Lessard CJ, Li H, Rasmussen A, Sivils KL, Scofield RH. Sjögren's Syndrome without focal lymphocytic infiltration of the salivary glands. J Rheumatol, 2019 May, PMID: 31092717

Towner RA, Smith N, Saunders D, Brown CA, Cai X, Ziegler J, Mallory S, Dozmorov MG, Coutinho De Souza P, Wiley G, Kim K, Kang S, Kong DS, Kim YT, Fung KM, Wren JD, Battiste J. OKN-007 Increases temozolomide (TMZ) Sensitivity and Suppresses TMZ-Resistant Glioblastoma (GBM) Tumor Growth. Transl Oncol 12:320-335, 2019 February, PMID: 30468988, PMCID: PMC6251232

Unnikrishnan A, Freeman WM, Jackson J, Wren JD, Porter H, Richardson A. The role of DNA methylation in epigenetics of aging. Pharmacol Ther 195:172-185, 2019 March, PMID: 30419258, PMCID: PMC6397707

Valcarcel-Ares MN, Tucsek Z, Kiss T, Giles CB, Tarantini S, Yabluchanskiy A, Balasubramanian P, Gautam T, Galvan V, Ballabh P, Richardson A, Freeman WM, Wren JD, Deak F, Ungvari Z, Csiszar A. Obesity in Aging Exacerbates Neuroinflammation, Dysregulating Synaptic Function-Related Genes and Altering Eicosanoid Synthesis in the Mouse Hippocampus: Potential Role in Impaired Synaptic Plasticity and Cognitive Decline. J Gerontol A Biol Sci Med Sci 74:290-298, 2019 February, PMID: 29893815, PMCID: PMC6376091

Wood AC, Wren JD, Allison DB. The Need for Greater Rigor in Childhood Nutrition and Obesity Research. JAMA Pediatr, 2019 February, PMID: 30801651

Wren JD, Doerkson RJ, Toby IT, Nanduri B, Homayouni R, Manda P, Thakkar S. Proceedings of the 2018 MidSouth Computational Biology and Bioinformatics Society (MCBIOS) conference. BMC Bioinformatics 20:95, 2019 March, PMID: 30871470, PMCID: PMC6419330

Wren JD, Valencia A, Kelso J. Reviewer-coerced citation: Case report, update on journal policy, and suggestions for future prevention. Bioinformatics, 2019 January, PMID: 30698640, PMCID: PMC6748764

Yao Q, Wang L, Mittal R, Yan D, Richmond MT, Denyer S, Requena T, Liu K, Varshney GK, Lu Z, Liu X. Transcriptomic Analyses of Inner Ear Sensory Epithelia in Zebrafish. Anat Rec (Hoboken), 2019 December, PMID: 31883312

Zalles M, Smith N, Ziegler J, Saunders D, Remerowski S, Thomas L, Gulej R, Mamedova N, Lerner M, Fung KM, Chung J, Hwang K, Jin J, Wiley G, Brown C, Battiste J, Wren JD, Towner RA. Optimized monoclonal antibody treatment against ELTD1 for GBM in a G55 xenograft mouse model. J Cell Mol Med, 2019 December, PMID: 31863639, PMCID: PMC6991683

Ziegler J, Zalles M, Smith N, Saunders D, Lerner M, Fung KM, Patel M, Wren JD, Lupu F, Battiste J, Towner RA. Targeting ELTD1, an angiogenesis marker for glioblastoma (GBM), also affects VEGFR2: molecular-targeted MRI assessment. Am J Nucl Med Mol Imaging 9:93-109, 2019 February, PMID: 30911439, PMCID: PMC6420708