The Gene Regulation & Cell Proliferation Program is an interdisciplinary effort focused on understanding the mechanisms that govern both normal and cancerous cell growth. The researchers in this program combine traditional experimental biology with cutting-edge technology to gain significant insights into DNA replication, epigenetics, and RNA biology.
Research in the Gene Regulation and Cell Proliferation program explores how these cellular processes drive the pathogenesis of human cancer. Scientists in this Program have identified numerous epigenetic vulnerabilities in aggressive cancers. The Program has also discovered aberrantly expressed non-coding RNAs and splicing alterations that provide the rationale for a potential new class of cancer therapeutics. In addition, significant advances have been made in our understanding of the mechanisms and regulation of DNA replication.
The Program is increasingly extending its studies to single cell biology and cancer metabolism, in an effort to understand the complexity and diversity of tumor cell types. There are numerous interactions among Program members and clinical researchers both locally and around the world. As a result, researchers in the Gene Regulation and Cell Proliferation Program continue to make seminal discoveries about the mechanisms that govern cell proliferation.
Among the changes that occur during pregnancy, those affecting the breasts have been found to subsequently modify breast cancer risk. My laboratory investigates how the signals present during pregnancy permanently alter the way gene expression is controlled and how these changes affect normal and malignant mammary development.
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, and how perturbations of ncRNAs and their regulators contribute to disease.
To ensure that cells function normally, tens of thousands of genes must be turned on or off together. To do this, regulatory molecules - transcription factors and non-coding RNAs – simultaneously control hundreds of genes. My group studies how the resulting gene networks function and how they can be compromised in human disease.
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.
From regulating gene expression to fighting off pathogens, biology uses DNA sequence information in many different ways. My research combines theory, computation, and experiment in an effort to better understand the quantitative relationships between DNA sequence and biological function. Much of my work is devoted to developing new methods in statistics and machine learning.
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.
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.
The immense amount of DNA, RNA and proteins that contribute to our genetic programs are precisely organized inside the cell¹s nucleus. My group studies how nuclear organization impacts gene regulation, and how misregulation of non-coding RNAs contributes to human diseases such as cancer.
Despite the development of preventive vaccines, human papillomaviruses (HPVs) still infect more than five million women each year, significantly increasing their risk of cervical cancer. I am working to identify how HPV multiplies so that we may develop drugs that can defeat the virus once it has infected an individual.
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.
Cancer cells achieve their pathogenicity by changing which genes are on and off. To maintain these changes in gene expression, cancer cells rely on proteins that interact with DNA or modify chromatin. My group investigates how such factors sustain the aberrant capabilities of cancer cells, thereby identifying new therapeutic targets.
The research of my lab focuses on normal and malignant hematopoietic stem and progenitor cells, specifically early erythroid progenitors and leukemic cells. We utilize both CRISPR/Cas functional genomic and forward chemical genomic approaches to uncover critical genes and small chemical compounds regulating the self-renewal of normal and malignant hematopoietic stem and progenitor cells. The ultimate goal of our research is to identify novel therapeutics for treatment-resistant hematopoietic malignancies including myelodysplastic syndrome and acute leukemia through targeting of novel self-renewal pathways and metabolic vulnerabilities.