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Gene Regulation and Inheritance

breast tissueThe Gene Regulation and Inheritance (GRI) Program investigates how DNA- and RNA-templated regulatory processes drive cancer development and lineage plasticity. The three main research themes of the GRI Program include: (1) defining cancer-specific roles of non-coding RNAs and RNA splicing; (2) revealing how chromatin regulation and genome inheritance support cancer development and maintenance; and (3) investigating how transcription factor master regulators drive cancer-specific gene programs.

Program Co-leaders

Adrian Krainer, Ph.D.

Justin Kinney, Ph.D.

The Gene Regulation and Inheritance Program combines experimental approaches with artificial intelligence (AI) research to uncover molecular mechanisms that control gene regulation and chromosomal inheritance. Program members are applying this knowledge toward innovative cancer therapeutic development. Areas of interest include uncovering mechanisms of splicing and RNA processing for developing antisense oligonucleotides as potential anti-cancer therapies, investigating chromatin-based regulation through histone modifications and nucleosome remodeling, and examining transcription factors through structural and mechanistic approaches. An expanding focus involves using genomic AI methods to decode how transcriptional control mechanisms are hijacked in cancer cells.

Major achievements include developing antisense oligonucleotides for diffuse intrinsic pontine glioma, identifying BRD8 as a druggable target in glioblastoma, and creating organoid platforms to study triple negative breast cancer. The Program has also developed genomic AI methods for deciphering transcriptional regulation and elucidated how chromatin remodeling complexes reprogram DNA methylation. The ten Cancer Center Shared Resources are essential for this research, notably the Animal, Flow Cytometry, Microscopy, Mass Spectrometry, Functional Genomics, and Sequencing Technologies & Analysis Shared Resources.

Building publication list.
Alexander Dobin

Alexander Dobin

Next generation sequencing technologies revolutionized many areas of genetics and molecular biology, enabling quantitative analyses of the entire genomes and paving the way for Personalized Medicine. We develop novel statistical methods and computational algorithms for multi-omics processing and integration, and leverage Big Genomic Data to elucidate various problems in precision health, such as genetic and epigenetic mechanisms of cancer development and progression, and clinical impact of functional variants.

Thomas Gingeras

Thomas Gingeras

Only a small portion of the RNAs encoded in any genome are used to make proteins. My lab investigates what these noncoding RNAs (ncRNAs) do within and outside of cells, where regulators of their expression are located in the genome. This is particularly important in cancer. Our laboratory works on endometrial cancer and its relationship to age and obesity.

Christopher Hammell

Christopher Hammell

As organisms develop, genes turn on and off with a precise order and timing, much like the order and duration of notes in a song. My group uses model organisms to understand the molecules that control the tempo of development. We also study how changes in the timing of gene expression contribute to diseases like cancer.

Leemor Joshua-Tor

Leemor Joshua-Tor

Our cells depend on thousands of proteins and nucleic acids that function as tiny machines: molecules that build, fold, cut, destroy, and transport all of the molecules essential for life. My group is discovering how these molecular machines work, looking at interactions between individual atoms to understand how they activate gene expression, DNA replication, and small RNA biology.

Justin Kinney

Justin Kinney

Research in the Kinney Lab combines mathematical theory, machine learning, and experiments in an effort to illuminate how cells control their genes. These efforts are advancing the fundamental understanding of biology and biophysics, as well as accelerating the discovery of new treatments for cancer and other diseases.

Peter Koo

Peter Koo

Deep learning has the potential to make a significant impact in basic biology and cancer, but a major challenge is understanding the reasons behind their predictions. My research develops methods to interpret this powerful class of black box models, with a goal of elucidating data-driven insights into the underlying mechanisms of sequence-function relationships.

Adrian R. Krainer

Adrian R. Krainer

Our DNA carries the instructions to manufacture all the proteins needed by a cell. After each gene is copied from DNA into RNA, the RNA message is "spliced" - an editing process involving precise cutting and pasting. I am interested in how splicing normally works, how it is altered in genetic diseases and cancer, and how we can correct these defects for therapy.

Rob Martienssen

Rob Martienssen

Chromosomes are covered with chemical modifications that help control gene expression. I study this secondary genetic code - the epigenome - and how it is guided by small mobile RNAs in plants and fission yeast. Our discoveries impact plant breeding and human health, and we use this and other genomic information to improve aquatic plants as a source of bioenergy.

David McCandlish

David McCandlish

Some mutations are harmful but others are benign. How can we predict the effects of mutations, both singly and in combination? Using data from experiments that simultaneously measure the effects of thousands of mutations, I develop computational tools to predict the functional impact of mutations and apply these tools to problems in protein design, molecular evolution, and cancer.

Alea A. Mills

Alea A. Mills

Cells employ stringent controls to ensure that genes are turned on and off at the correct time and place. Accurate gene expression relies on several levels of regulation, including how DNA and its associated molecules are packed together. I study the diseases arising from defects in these control systems, such as aging and cancer.

Lopa Mishra

Lopa Mishra

My research focuses on the continuum of science-driven clinical care by working on novel therapies and improved clinical outcomes, honing liver disease, metabolism/alcohol, obesity/addiction gastrointestinal cancers, inflammatory bowel disease, and neural regulation of disease and cancer, which links to the field of bioelectronic medicine.

Andrea Schorn

Andrea Schorn

Transposable elements make up half of our DNA. They control gene expression and have been a major evolutionary force in all organisms. The Schorn lab investigates how small RNAs identify and silence transposable elements when they become active during development and disease.

David L. Spector

David L. Spector

The immense amount of DNA, RNA and proteins that contribute to our genetic programs are precisely organized inside the cell's nucleus. My group studies how nuclear organization impacts gene regulation, and how misregulation of non-coding RNAs contributes to human diseases such as cancer.

Bruce Stillman

Bruce Stillman

Every time a cell divides, it must accurately copy its DNA. With 3 billion “letters” in the human genome, this is no small task. My studies reveal the many steps and molecular actors involved, as well as how errors in DNA replication are involved in diseases that range from cancer to rare genetic disorders.