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Gene Regulation and Inheritance

breast tissueThe Gene Regulation and Inheritance Program focuses on revealing basic mechanisms governing the regulation of gene expression and cell inheritance at the DNA, RNA, and protein levels, and on discovering how these mechanisms are perturbed to influence the initiation and/or progression of cancer. A major strength of the Program is the innovative science that is yielding novel insights into non-coding RNA species, RNA splicing, chromatin biology, and cell-cycle control. Alterations in these processes are critical features of the transformed phenotype. Although fundamental research is the central to this Program, many discoveries are being translated toward the clinic, due in part to the strong strategic alliance with clinical partners.

Program Co-leaders

Adrian Krainer, Ph.D.

Justin Kinney, Ph.D.

Members of the Gene Regulation and Inheritance Program share an interest in uncovering the mechanisms governing inheritance of cell state as well as mechanisms of transcriptional and post-transcriptional regulation, and on understanding how those mechanisms are altered in cancer cells. The Program has three main focus areas: (1) elucidating fundamental mechanisms governing the regulation of non-coding RNAs, transcription, and cell inheritance; (2) determining how transcriptional and post-transcriptional control are dysregulated in cancer; and (3) developing therapeutic agents and biological systems to target pro-tumorigenic alterations in transcriptional and post-transcriptional regulators. The Program also has expertise in computational analysis of gene expression patterns, mRNA splicing, and mutation identification which is being used to uncover alterations that drive aberrant gene regulation and impact all three focus areas. Program members combine cell, molecular biology, biochemical, structural biology, computational, and genetic approaches. The Program is enhanced by the excellent Cancer Center Shared Resources, especially the Animal, Sequencing Technologies & Analysis, Flow Cytometry, Microscopy, and Mass Spectrometry 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 molecules 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 cancer.

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.

Lingbo Zhang

Lingbo Zhang

The research in the Zhang laboratory centers on normal and malignant stem and progenitor cells in the hematopoietic system and decodes the role of metabolites, including micronutrients and neurotransmitters, in the tumor microenvironment and their genetic effectors in regulating hematologic malignancies. The ultimate goal is to understand how environmental signals such as diets and nervous system activities modulate development and cancers.