Darren Cusanovich, PhD

Associate Professor, Cellular and Molecular Medicine

Associate Professor, BIO5 Institute

Office Room Number: BSRL 421

Links

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 leads to complex disease. The particular disease model that we focus on is asthma, a complex disease affecting ~10-20% of the population that involves many cell types of the lung and immune system and offers exquisitely detailed examples of gene-environment interactions that influence disease outcomes. 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.

Teaching Interests

Developing new single-cell genomic technologies and applying those technologies to animal models and primary samples to better understand the gene regulatory basis of development and disease.

Publications

Zhang, Hao, et al. “Txci-ATAC-Seq: A Massive-Scale Single-Cell Technique to Profile Chromatin Accessibility.”. Genome Biol, vol. 25, no. 1, Mar. 2024, p. 78, https://doi.org/10.1186/s13059-023-03150-1.

Adelus, Maria L, et al. “Single Cell ’omic Profiles of Human Aortic Endothelial Cells and Human Atherosclerotic Lesions Reveals Heterogeneity of Endothelial Subtype and Response to Activating Perturbations.”. BioRxiv, Jan. 2024, https://doi.org/10.1101/2023.04.03.535495.

Iannuzo, Natalie, et al. “CC16 Drives VLA-2-Dependent SPLUNC1 Expression.”. Front Immunol, vol. 14, 2023, p. 1277582, https://doi.org/10.3389/fimmu.2023.1277582.

Kang, HyunJin, et al. “Evaluation of Swab-Seq As a Scalable, Sensitive Assay for Community Surveillance of SARS-CoV-2 Infection.”. Sci Rep, vol. 12, no. 1, Feb. 2022, p. 3047, https://doi.org/10.1038/s41598-022-06901-5.

Watson, Adam W, et al. “Breast Tumor Stiffness Instructs Bone Metastasis via Maintenance of Mechanical Conditioning.”. Cell Rep, vol. 35, no. 13, Jan. 2021, p. 109293, https://doi.org/10.1016/j.celrep.2021.109293.

Domcke, Silvia, et al. “A Human Cell Atlas of Fetal Chromatin Accessibility.”. Science, vol. 370, no. 6518, Nov. 2020, https://doi.org/10.1126/science.aba7612.

Chang, Eugene H, et al. “RV Infections in Asthmatics Increase ACE2 Expression and Cytokine Pathways Implicated in COVID-19”. Am J Respir Crit Care Med, July 2020, https://doi.org/10.1164/rccm.202004-1343LE.

Rai, Vivek, et al. “Single-Cell ATAC-Seq in Human Pancreatic Islets and Deep Learning Upscaling of Rare Cells Reveals Cell-Specific Type 2 Diabetes Regulatory Signatures.”. Mol Metab, vol. 32, Feb. 2020, pp. 109-21, https://doi.org/10.1016/j.molmet.2019.12.006.

Allan, Christopher M, et al. “An Upstream Enhancer Regulates Expression in a Tissue-Specific Manner.”. J Lipid Res, vol. 60, no. 4, Apr. 2019, pp. 869-7, https://doi.org/10.1194/jlr.M091322.

Cusanovich, Darren A, et al. “A Single-Cell Atlas of In Vivo Mammalian Chromatin Accessibility.”. Cell, July 2018, https://doi.org/10.1016/j.cell.2018.06.052.

Pliner, Hannah A, et al. “Cicero Predicts Cis-Regulatory DNA Interactions from Single-Cell Chromatin Accessibility Data.”. Mol Cell, June 2018, https://doi.org/10.1016/j.molcel.2018.06.044.