@article {119,
	title = {Identification of Required Host Factors for SARS-CoV-2 Infection in Human Cells.},
	journal = {Cell},
	volume = {184},
	year = {2021},
	month = {2021 01 07},
	pages = {92-105.e16},
	abstract = {<p>To better understand host-virus genetic dependencies and find potential therapeutic targets for COVID-19, we performed a genome-scale CRISPR loss-of-function screen to identify host factors required for SARS-CoV-2 viral infection of human alveolar epithelial cells. Top-ranked genes cluster into distinct pathways, including the vacuolar ATPase proton pump, Retromer, and Commander complexes. We validate these gene targets using several orthogonal methods such as CRISPR knockout, RNA interference knockdown, and small-molecule inhibitors. Using single-cell RNA-sequencing, we identify shared transcriptional changes in cholesterol biosynthesis upon loss of top-ranked genes. In addition, given the key role of the ACE2 receptor in the early stages of viral entry, we show that loss of RAB7A reduces viral entry by sequestering the ACE2 receptor inside cells. Overall, this work provides a genome-scale, quantitative resource of the impact of the loss of each host gene on fitness/response to viral infection.</p>},
	keywords = {A549 Cells, Alveolar Epithelial Cells, Angiotensin-Converting Enzyme 2, Biosynthetic Pathways, Cholesterol, Clustered Regularly Interspaced Short Palindromic Repeats, COVID-19, Endosomes, Gene Expression Profiling, Gene Knockdown Techniques, Gene Knockout Techniques, Genome-Wide Association Study, Host-Pathogen Interactions, Humans, rab GTP-Binding Proteins, rab7 GTP-Binding Proteins, RNA Interference, SARS-CoV-2, Single-Cell Analysis, Viral Load},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2020.10.030},
	author = {Daniloski, Zharko and Jordan, Tristan X and Wessels, Hans-Hermann and Hoagland, Daisy A and Kasela, Silva and Legut, Mateusz and Maniatis, Silas and Mimitou, Eleni P and Lu, Lu and Geller, Evan and Danziger, Oded and Rosenberg, Brad R and Phatnani, Hemali and Smibert, Peter and Lappalainen, Tuuli and tenOever, Benjamin R and Sanjana, Neville E}
}
@article {27,
	title = {Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms.},
	journal = {Cell},
	volume = {170},
	year = {2017},
	month = {2017 Jun 29},
	pages = {199-212.e20},
	abstract = {<p>Type 2 diabetes (T2D) affects Latinos at twice the~rate~seen in populations of European descent. We~recently identified a risk haplotype spanning SLC16A11 that explains \~{}20\% of the increased T2D prevalence in Mexico. Here, through genetic fine-mapping, we define a set of tightly linked variants likely to contain the causal allele(s). We show that variants on the T2D-associated haplotype have two distinct effects: (1) decreasing SLC16A11 expression in liver and (2) disrupting a key interaction with basigin, thereby reducing cell-surface localization. Both independent mechanisms reduce SLC16A11 function and suggest SLC16A11 is the causal gene at~this locus. To gain insight into how SLC16A11 disruption impacts T2D risk, we demonstrate that SLC16A11 is a proton-coupled monocarboxylate transporter and that genetic perturbation of SLC16A11 induces changes in fatty acid and lipid metabolism that are associated with increased T2D risk. Our findings suggest that increasing SLC16A11 function could be therapeutically beneficial for T2D. VIDEO ABSTRACT.</p>},
	keywords = {Basigin, Cell Membrane, Chromosomes, Human, Pair 17, Diabetes Mellitus, Type 2, Gene Knockdown Techniques, Haplotypes, Hepatocytes, Heterozygote, Histone Code, Humans, Liver, Models, Molecular, Monocarboxylic Acid Transporters},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2017.06.011},
	author = {Rusu, Victor and Hoch, Eitan and Mercader, Josep M and Tenen, Danielle E and Gymrek, Melissa and Hartigan, Christina R and DeRan, Michael and von Grotthuss, Marcin and Fontanillas, Pierre and Spooner, Alexandra and Guzman, Gaelen and Deik, Amy A and Pierce, Kerry A and Dennis, Courtney and Clish, Clary B and Carr, Steven A and Wagner, Bridget K and Schenone, Monica and Ng, Maggie C Y and Chen, Brian H and Centeno-Cruz, Federico and Zerrweck, Carlos and Orozco, Lorena and Altshuler, David M and Schreiber, Stuart L and Florez, Jose C and Jacobs, Suzanne B R and Lander, Eric S}
}
