Massachusetts Institute of Technology

Beth Israel Deaconess Medical Center, Inc.

The Broad Institute, Inc.

European Molecular Biology Laboratory

Liu, Yaping

Adalsteinsson, Viktor

Zhang, Zhizhuo

Kellis, Manolis

Manolis Kellis

Zhizhuo Zhang

Melina Christine Claussnitzer

Timothy Kuan-Ta Lu

Li-Huei Tsai

Viktor A Adalsteinsson

Joel Blanchard

Djuna Von Maydell

Sandeep Nuckchady

Matheus Victor

Liang He

Xinchen Wang

Yaping Liu

Leyla Akay

Lauren Huang

Audrey Effenberger

Jan Korbel

Jicong Cao

Dianbo Liu

Eva Maria Novoa Pardo

Anne Kim

Jose Davila Velderrain

The present disclosure provides methods of inhibiting amyloid synthesis in a subject using cyclodextrin and analogs thereof. Small molecules (cyclodextrin) reverse APOE4-associated cholesterol phenotypes and lead to significantly improved myelination both human in vitro cultures and APOE4 targeted replacement mice. This demonstrates that APOE4 alters cholesterol synthesis and transport in oligodendrocytes which impairs myelination. Collectively, this work uncovers a pathogenic role of APOE4 in oligodendrocytes and myelination and enables therapeutic opportunities for Alzheimer's Disease.

APOE4 impairs myelination via altered cholesterol biosynthesis and transport in oligodendroglia

Embodiments disclosed herein provide a general, scalable, high-throughput, and high-resolution approach for experimental dissection of regulatory regions and driver nucleotides in the context of human biology and disease. Applicants present HiDRA, a novel high-resolution global screen for transcriptional regulatory activity in accessible chromatin regions, enabling high-efficiency, high-throughput, and high-resolution inference of regulatory activity.

Methods for high-resolution genome-wide functional dissection of transcriptional regulatory regions

Disclosed herein are novel 5′ UTR sequences that can be used to control gene expression in various contexts. Also disclosed herein are methods of engineering 5′ UTR sequences and methods and kits for screening 5′ UTR sequences for a property of interest.

Synthetic 5' UTR sequences, and high-throughput engineering and screening thereof

As described below, disclosed herein are methods of analyzing DNA methylation in cell-free DNA (cfDNA) and genomic DNA (gDNA) from sequencing data.

Methods for genome characterization

Described herein are a secure system for sharing private data and related systems and methods for incentivizing and validating private data sharing. In some embodiments, private data providers may register to selectively share private data under controlled sharing conditions. The private data may be cryptographically secured using encryption information corresponding to one or more secure execution environments. To demonstrate to the private data providers that the secure execution environment is secure and trustworthy, attestations demonstrating the security of the secure execution environment may be stored in a distributed ledger (e.g., a public blockchain). Private data users that want access to shared private data may publish applications for operating on the private data to a secure execution environment and publish, in a distributed ledger, an indication that the application is available to receive private data. The distributed ledger may also store sharing conditions under which the private data will be shared.

Systems and methods for crowdsourcing, analyzing, and/or matching personal data

Provided herein is a pathway for adipocyte energy consumption regulation involving ARID5B, genetic variant rs1421085, IRX3, and IRX5. Compositions and methods for modulating the pathway in vitro and in vivo for anti-cachectic and anti-obesity effects are provided. Methods of identifying subjects at risk of developing a disorder mediated by a dysregulation of the energy consumption pathway are also provided.

Compositions and methods for manipulation of adipocyte energy consumption regulatory pathway

Growing community of inventors

Brookline, MA, United States of America

Manolis Kellis