Research

Our lab is interested in understanding how the human genome regulates itself to bring about all of the cellular diversity present in our bodies. In addition, we are interested in how genetic variation and environmental exposures in human populations impact that regulation and sometimes lead to complex disease. The particular disease model that we focus on is asthma, a complex disease affecting ~10-20% of the population. The reasons we think that single-cell approaches would be particularly applicable to asthma are: (1) the disease involves complex interactions between many cell types of the lung and immune system that are difficult to model; And (2) there are several exquisitely detailed examples of gene-environment interactions that influence asthma outcomes many years later, but we still know relatively little about the molecular mechanisms that lead from exposure to disease. To study these phenomena, we use single-cell genomics technologies so that we can evaluate the impact of genetic and environmental variability from the perspective of whole tissues rather than having to isolate individual cell types or use simplistic cellular models. Working at the nexus of functional genomics, computational biology, and cellular biology, our group is both experimental and computational and often has to develop novel technologies or methods to address our research questions.

News

October 28, 2022: Lacey Cigan starts a rotation in the lab. Welcome Lacey!

July 29, 2022: Darren was interviewed on the Tucson NPR affiliate! It was episode 332 of "Arizona Science". Have a listen here!

March 17, 2022: Hao's paper on ATAC-seq conditions is published in BMC Genomics!

February 23, 2022: HyunJin's paper on Swab-seq is published in Scientific Reports!

November 15, 2021: Darren was promoted from Research Assistant Professor to Assistant Professor!

November 12, 2020: The Cusanovich Lab, along with collaborators at UW, published a new single-cell ATAC-seq assay in Science. The article also includes an atlas of fetal tissues at single-cell resolution. More information is available here. You can read the paper here.

October 26, 2020: Jiacheng Ding starts a rotation in the lab. Welcome Jiacheng!

August 21, 2020: We received official notice today that we've been awarded a Maximizing Investigators’ Research Award for Early Stage Investigators (ESI MIRA) R35 from NIGMS!

June 4, 2020: Holly was awarded a position on the Interdisciplinary Training in Cardiovascular Research (T32) training grant!

January 31, 2020: Darren received a UA Health Sciences Career Development Award!

November 18, 2019: HyunJin Kang starts in the lab. Welcome HyunJin!

June 10, 2019: Holly Welfley starts a rotation in the lab. Welcome Holly!

October 22, 2018: Hao Zhang starts a rotation in the lab. Welcome Hao!

August 2, 2018: Darren is first author on a paper published in Cell. See coverage here and here. You can access the paper here.

June 18, 2018: We opened our doors in the Biosciences Research Labs at UofA!

People

	Darren Cusanovich Assistant Professor, Cellular and Molecular Medicine (CMM) Assistant Research Scientist, Asthma & Airway Disease Research Center (A2DRC) Darren received his B.S. in Music Business (yes, Music Business!!) from Loyola University New Orleans in 2002. After a brief stint in the music industry in Los Angeles, he realized that his true passion was genomics (it's a long story). So, Darren spent a few years in Donata Vercelli's Lab here at the University of Arizona - his first exposure to asthma genomics research. Darren then got his Ph.D. in Human Genetics from The University of Chicago (in Yoav Gilad's lab). While there, Darren studied how genetic variation in human populations perturbs gene expression and can lead to complex disease susceptibilities. Darren then did his postdoctoral research in Jay Shendure's lab at the University of Washington. While in Seattle, he developed a novel single-cell chromatin accessibility assay and applied it to several model systems to study the variation in gene regulatory landscapes present in complex tissues. In 2018, Darren accepted a position here at the UofA in CMM and the A2DRC. darrenc@arizona.edu CV Pubmed
	HyunJin Kang Research Scientist hjkang@email.arizona.edu
	Jiacheng Ding Graduate Student (GPMM) jiachengd@email.arizona.edu
	Holly Welfley Graduate Student (CBIO) hwelfley@email.arizona.edu
	Hao Zhang Graduate Student (GPMM) haozhang1@email.arizona.edu
	You? Looking for an exciting opportunity? Do you like the idea of pursuing cutting-edge genomics research? Do you like the idea of living in a place with lots of sunshine, lots of opportunity for outdoor activities, vibrant southwestern culture, easy commutes, and an affordable cost living? E-mail us! We are always looking for talented, enthusiastic people to work with. **We are always open to having talented people join the team and help drive our research program. If you're interested in being a part of our group (at any level) feel free to drop us a line.**

Publications

"*" denotes equal contribution.

2023

Zhang H*, Mulqueen RM*, Iannuzo N, Farrera DO, Polverino F, Galligan JJ, Ledford JG, Adey AC*, Cusanovich DA*. txci-ATAC-seq, a massive-scale single-cell technique to profile chromatin accessibility. BioRxiv. 2023 May 14. [preprint]

Kang H, Fitch JC, Varghese RP, Thorne CA, Cusanovich DA. SGRN: A Cas12a-driven Synthetic Gene Regulatory Network System. BioRxiv. 2023 May 8. [preprint]

Adelus ML, Ding J, Tran BT, Conklin AC, Golebiewski AK, Stolze LK, Whalen MB, Cusanovich DA, Romanoski CE. Multiomics of human aortic endothelial cells reveals cell subtypes with heterogeneous responses to canonical endothelial-to-mesenchymal perturbations. BioRxiv. 2023 Apr 6. [preprint]

2022

Welfley H, Kylat R, Zaghloul N, Halonen M, Martinez FD, Ahmed M, Cusanovich DA. Mapping fetal myeloid differentiation in airway samples from premature neonates with single-cell profiling. BioRxiv Preprint. 2022 Jul 10. [journal]

Zhang H, Rice ME, Alvin JW, Farrera-Gaffney D, Galligan JJ, Johnson MDL, Cusanovich DA. Extensive evaluation of ATAC-seq protocols for native or formaldehyde-fixed nuclei. BMC Genomics. 2022 Mar 17; 23:214. [journal]

Kang H, Allison S, Spangenberg A, Carr T, Sprissler R, Halonen M, Cusanovich DA. Evaluation of Swab-Seq as a scalable, sensitive assay for community surveillance of SARS-CoV-2 infection. Scientific Reports. 2022 Feb 23; 12:3047. [journal]

2021

Watson AW, Grant A, Parker SS, Hill S, Whalen MB, Chakrabarti J, Harman MW, Roman MR, Forte BL, Gowan CC, Castro-Portuguez R, Stolze LK, Franck C, Cusanovich DA , Zavros Y, Padi M, Romanoski C, Mouneimne G. Breast tumor stiffness instructs bone metastasis via maintenance of mechanical conditioning. Cell Reports. 2021 Jun 29; 35(13):109293. [journal]

Durham TJ, Daza RM, Gevirtzman L, Cusanovich DA, Bolonduro O, Noble WS, Shendure J, Waterston RH. Comprehensive characterization of tissue-specific chromatin accessibility in L2 C. elegans nematodes. Genome Research. 2021 Oct; 31(10):1952-1969. [journal]

2020

Domcke S^*, Hill AJ^*, Daza RM^*, Cao J, O’Day DR, Pliner HA, Aldinger KA, Pokholok D, Zhang F, Milbank JH, Zager MA, Glass IA, Steemers FJ, Doherty D, Trapnell C^*, Cusanovich DA^*, Shendure J^*. A human cell atlas of fetal chromatin accessibility. Science. 2020 Nov 13; 370(6518):eaba7612. [journal]

Chang EH, Willis AL, Romanoski CE, Cusanovich DA, Pouladi N, Li J, Lussier YA, Martinez FD. RV Infections in Asthmatics Increase ACE2 Expression and Cytokine Pathways Implicated in COVID-19. American Journal of Respiratory and Critical Care Medicine. 2020 Sep 1; 202(5):753-755. [journal]

Rai V, Quang DX, Erdos MR, Cusanovich DA, Daza RM, Narisu N, Zou LS, Didion JP, Guan Y, Shendure J, Parker SCJ, Collins FS. Single-cell ATAC-Seq in human pancreatic islets and deep learning upscaling of rare cells reveals cell-specific type 2 diabetes regulatory signatures. Molecular Metabolism. 2020 Feb 1; 32:109-121. [journal]

2019

Allan CM, Heizer PJ, Tu Y, Sandoval NP, Jung RS, Morales JE, Sajti E, Troutman TD, Saunders TL, Cusanovich DA, Beigneux AP, Romanoski CE, Fong LG, Young SG. An upstream enhancer regulates Gpihbp1 expression in a tissue-specific manner. Journal of Lipid Research. 2019 Apr 1; 60(4):869-879. [journal]

2018

Cao J, Cusanovich DA, Ramani V, Aghamirzaie D, Pliner HA, Hill AJ, Daza RM, McFaline-Figueroa JL, Packer JS, Christiansen L, Steemers FJ, Adey AC, Trapnell C, Shendure J. Joint profiling of chromatin accessibility and gene expression in thousands of single cells. Science. 2018 Sep 28; 361(6409):1380-1385. [journal]

Pliner HA, Packer JS, McFaline-Figueroa JL, Cusanovich DA, Daza RM, Aghamirzaie D, Srivatsan S, Qiu X, Jackson D, Minkina A, Adey AC, Steemers FJ, Shendure J, Trapnell C. Cicero Predicts cis-Regulatory DNA Interactions from Single-Cell Chromatin Accessibility Data. Molecular Cell. 2018 Sep 6;71(5):858-871.e8. [journal]

Cusanovich DA^*, Hill AJ^*, Aghamirzaie D, Daza RM, Pliner HA, Berletch JB, Filippova GN, Huang X, Christiansen L, DeWitt WS, Lee C, Regalado SG, Read DF, Steemers FJ, Disteche CM, Trapnell C, Shendure J. A Single-Cell Atlas of In Vivo Mammalian Chromatin Accessibility. Cell. 2018 Aug 23; 174(5):1309-1324.e18. [journal]

Cusanovich DA^*, Reddington JP^*, Garfield DA^*, Daza R, Aghamirzaie D, Marco-Ferreres R, Pliner HA, Christiansen L, Qiu X, Steemers FJ, Trapnell C, Shendure J, Furlong EEM. The cis-regulatory dynamics of embryonic development at single-cell resolution. Nature. 2018 Mar 22; 555(7697):538-542. [journal]

2017

Cao J, Packer JS, Ramani V, Cusanovich DA, Huynh C, Daza R, Qiu X, Lee C, Furlan SN, Steemers FJ, Adey A, Waterston RH, Trapnell C, Shendure J. Comprehensive single-cell transcriptional profiling of a multicellular organism. Science. 2017 Aug 18; 357(6352):661-667. [journal]

Gasperini M, Findlay GM, McKenna A, Milbank JH, Lee C, Zhang MD, Cusanovich DA, Shendure J. CRISPR/Cas9-Mediated Scanning for Regulatory Elements Required for HPRT1 Expression via Thousands of Large, Programmed Genomic Deletions. American Journal of Human Genetics. 2017 Aug 3; 101(2):192-205. [journal]

2016

Ramani V, Cusanovich DA, Hause RJ, Ma W, Qiu R, Deng X, Blau CA, Disteche CM, Noble WS, Shendure J, Duan Z. Mapping 3D genome architecture through in situ DNase Hi-C. Nature Protocols. 2016 Nov; 11(11):2104-2121. [journal]

Cusanovich DA, Caliskan M, Billstrand C, Michelini KJ, Chavarria C, De Leon S, Mitrano A, Lewellyn N, Elias JA, Chupp GL, Lang RM, Shah SJ, DeCara JM, Gilad Y, Ober C. Integrated Analyses of Gene Expression and Genetic Association Studies in a Founder Population. Human Molecular Genetics. 2016 Feb 29; 25(10):2104-2112. [journal]

2015

Davenport ER, Cusanovich DA, Michelini K, Barreiro LB, Ober C, Gilad Y. Genome-Wide Association Studies of the Human Gut Microbiota. PLoS One. 2015 Nov 3; 10(11):e0140301. [journal]

Cusanovich DA, Daza R, Adey A, Pliner H, Christiansen L, Gunderson KL, Steemers FJ, Trapnell C, Shendure J. Multiplex single-cell profiling of chromatin accessibility by combinatorial cellular indexing. Science. 2015 May 22; 348(6237):910-914. [journal]

2014

Cusanovich DA, Pavlovic B, Pritchard JK, Gilad, Y. The functional consequences of variation in transcription factor binding. PLoS Genetics. 2014 Mar 6; 10(3):e1004226. [journal]

2013

Khan Z, Ford MJ, Cusanovich DA, Mitrano A, Pritchard JK, Gilad Y. Primate transcript and protein expression levels evolve under compensatory selection pressures. Science. 2013 Nov 29; 342(6162):1100-1104. [journal]

2012

Iskow RC, Gokcumen O, Abyzov A, Malukiewicz J, Zhu Q, Sukumar AT, Pai AA, Mills RE, Habegger L, Cusanovich DA, Rubel MA, Perry GH, Gerstein M, Stone AC, Gilad Y, Lee C. Regulatory element copy number differences shape primate expression profiles. Proceedings of the National Academy of Sciences. 2012 Jul 31; 109(31):12656-61. [journal]

Cusanovich DA, Billstrand C, Zhou X, Chavarria C, De Leon S, Michelini K, Pai AA, Ober C, Gilad Y. The combination of a genome-wide association study of lymphocyte count and analysis of gene expression data reveals novel asthma candidate genes. Human Molecular Genetics. 2012 May 1; 21(9):2111-23. [journal]

2011

Caliskan M, Cusanovich DA, Ober C, Gilad Y. The effects of EBV transformation on gene expression levels and methylation profiles. Human Molecular Genetics. 2011 Apr 15; 20(8):1643-52. [journal]

2009

Ober C, Nord AS, Thompson EE, Pan L, Tan Z, Cusanovich D, Sun Y, Nicolae R, Edelstein C, Schneider DH, Billstrand C, Pfaffinger D, Phillips N, Anderson RL, Philips B, Rajagopalan R, Hatsukami TS, Rieder MJ, Heagerty PJ, Nickerson DA, Abney M, Marcovina S, Jarvik GP, Scanu AM, Nicolae DL. Genome-wide association study of plasma lipoprotein(a) levels identifies multiple genes on chromosome 6q. Journal of Lipid Research. 2009 May; 50(5):798-806. [journal]

Contact

Asthma & Airway Disease Research Center
University of Arizona Biosciences Research Labs, Room 421
1230 N Cherry Avenue
Tucson, AZ 85721
Office: 520-626-8639
Lab: 520-626-6862
darrenc@email.arizona.edu

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