Eric S. Lander
Massachusetts Institute of Technology
Publications 797
#1Eitan Hoch (Broad Institute)H-Index: 2
#2Jose C. Florez (Broad Institute)H-Index: 73
Last.Suzanne B.R. Jacobs (Broad Institute)H-Index: 5
view all 4 authors...
Summary Human genetic variants in SLC16A11 are associated with increased risk of type 2 diabetes (T2D). We previously identified two distinct mechanisms through which co-inherited T2D-risk coding and non-coding variants disrupt SLC16A11 expression and activity, thus implicating reduced SLC16A11 function as the disease-relevant direction of effect. In a recent publication, Zhao et al. (2019a) argue that human SLC16A11 coding variants confer gain of function, basing their conclusions on phenotypic...
1 CitationsSource
#1Alexander G. Bick (Harvard University)H-Index: 19
#2Joshua S. Weinstock (UM: University of Michigan)H-Index: 1
Last.Sekar Kathiresan (Broad Institute)H-Index: 106
view all 123 authors...
Age is the dominant risk factor for most chronic human diseases; yet the mechanisms by which aging confers this risk are largely unknown. Recently, the age-related acquisition of somatic mutations in regenerating hematopoietic stem cell populations was associated with both hematologic cancer incidence and coronary heart disease prevalence. Somatic mutations with leukemogenic potential may confer selective cellular advantages leading to clonal expansion, a phenomenon termed 9Clonal Hematopoiesis ...
1 CitationsSource
#1C. A. Painter (Harvard University)
#2Esha Jain (Broad Institute)H-Index: 7
Last.Nikhil WagleH-Index: 30
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ABSTRACT Despite collectively accounting for 25% of tumors in U.S. adults, rare cancers have significant unmet clinical needs as they are difficult to study due to low incidence and geographically dispersed patient populations. We sought to assess whether a patient-partnered research approach using online engagement can overcome these challenges and accelerate scientific discovery in rare cancers, focusing on angiosarcoma (AS), an exceedingly rare sarcoma with a dismal prognosis and an annual U....
#1Brian Cleary (Broad Institute)H-Index: 7
#2Evan Murray (Broad Institute)H-Index: 1
Last.Aviv Regev (MIT: Massachusetts Institute of Technology)H-Index: 110
view all 11 authors...
Gaining a systematic molecular understanding of tissue physiology in health and disease will require the ability to rapidly profile the abundances of many genes at high resolution over large tissue volumes. Many current methods of imaging transcriptomics are based on single-molecule fluorescent in situ hybridization, with barcodes to allow multiplexing across genes. These approaches have serious limitations with respect to (i) the number of genes that can be studied and (ii) imaging time, due to...
1 CitationsSource
Sequencing-based studies have identified novel risk genes associated with severe epilepsies and revealed an excess of rare deleterious variation in less-severe forms of epilepsy. To identify the shared and distinct ultra-rare genetic risk factors for different types of epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilepsy-affected individuals and 8,436 controls of European ancestry. We focused on three phenotypic groups: severe developmental and epileptic encephalopa...
6 CitationsSource
#1Eachan O. Johnson (Broad Institute)H-Index: 1
#2Emily LaVerriere (Broad Institute)H-Index: 1
Last.Deborah T. Hung (Broad Institute)H-Index: 37
view all 44 authors...
New antibiotics are needed to combat rising levels of resistance, with new Mycobacterium tuberculosis (Mtb) drugs having the highest priority. However, conventional whole-cell and biochemical antibiotic screens have failed. Here we develop a strategy termed PROSPECT (primary screening of strains to prioritize expanded chemistry and targets), in which we screen compounds against pools of strains depleted of essential bacterial targets. We engineered strains that target 474 essential Mtb genes and...
7 CitationsSource
#1Moran Dvela-Levitt (Broad Institute)H-Index: 2
#2Maria Kost-Alimova (Broad Institute)H-Index: 4
Last.Anna Greka (Broad Institute)H-Index: 18
view all 38 authors...
Summary Intracellular accumulation of misfolded proteins causes toxic proteinopathies, diseases without targeted therapies. Mucin 1 kidney disease (MKD) results from a frameshift mutation in the MUC1 gene (MUC1-fs). Here, we show that MKD is a toxic proteinopathy. Intracellular MUC1-fs accumulation activated the ATF6 unfolded protein response (UPR) branch. We identified BRD4780, a small molecule that clears MUC1-fs from patient cells, from kidneys of knockin mice and from patient kidney organoid...
5 CitationsSource
#1Maris Alver (UT: University of Tartu)H-Index: 11
#2Marili Palover (UT: University of Tartu)H-Index: 1
Last.Tonu Esko (UT: University of Tartu)H-Index: 89
view all 22 authors...
Large-scale, population-based biobanks integrating health records and genomic profiles may provide a platform to identify individuals with disease-predisposing genetic variants. Here, we recall probands carrying familial hypercholesterolemia (FH)-associated variants, perform cascade screening of family members, and describe health outcomes affected by such a strategy. The Estonian Biobank of Estonian Genome Center, University of Tartu, comprises 52,274 individuals. Among 4776 participants with e...
2 CitationsSource
#1Bradley E. Poulsen (Broad Institute)H-Index: 8
#2Rui Yang (Broad Institute)H-Index: 1
Last.Deborah T. Hung (Broad Institute)H-Index: 37
view all 10 authors...
Genomics offered the promise of transforming antibiotic discovery by revealing many new essential genes as good targets, but the results fell short of the promise. While numerous factors contributed to the disappointing yield, one factor was that essential genes for a bacterial species were often defined based on a single or limited number of strains grown under a single or limited number of in vitro laboratory conditions. In fact, the essentiality of a gene can depend on both the genetic backgr...
3 CitationsSource
#1Amit KheraH-Index: 52
#2Mark Chaffin (Broad Institute)H-Index: 12
Last.Sekar KathiresanH-Index: 106
view all 19 authors...
Summary Severe obesity is a rapidly growing global health threat. Although often attributed to unhealthy lifestyle choices or environmental factors, obesity is known to be heritable and highly polygenic; the majority of inherited susceptibility is related to the cumulative effect of many common DNA variants. Here we derive and validate a new polygenic predictor comprised of 2.1 million common variants to quantify this susceptibility and test this predictor in more than 300,000 individuals rangin...
27 CitationsSource